bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-acquired pneumonia through Enterobacteriaceae andPseudomonas aeruginosa: diagnosis, incidence and predictors
Authors: von Baum H. , Welte T. , Marre R. , Suttorp N. , Ewig S.
Published: August 2009

The aim of the present study was to determine the relevance of the presence of Enterobacteriaceae (EB) andPseudomonas aeruginosa(PA) in patients with community-acquired pneumonia (CAP) and how the true incidence of these pathogens can be assessed.

Based on prospective data from 5,130 patients with CAP included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), the incidence, clinical characteristics, outcome and predictors of patients with CAP due to EB and PA were studied applying strict case definitions.

The incidence of EB was 67 (1.3%) out of 5,130, including 27 patients with bacteraemia. PA was found in 22 (0.4%) out of 5,130 patients. These microorganisms were judged to be indeterminate pathogens in an additional 172 and 27 isolates, respectively. Patients with indeterminate pathogens differed considerably from those with definite isolates in terms of clinical presentation, comorbidity, pneumonia severity and outcome. Independent risk factors for EB included cardiac and cerebrovascular disease, and for PA chronic respiratory disease and enteral tube feeding. The 30-day mortality was significantly higher in patients with definite pathogens.

In the present large population, the incidence of CAP due to EB/ PA was low. The risk of the presence of these pathogens can be assessed using several predictors, which may identify those patients in need of an extended diagnostic work-up and initial antimicrobial treatment.
Myeloid RelA regulates pulmonary host defense networks
Authors: Hess C. , Herr C. , Beisswenger C. , Zakharkina T. , Schmid R. M. , Bals R.
Published: August 2009

The pulmonary innate immune system in the respiratory tract eliminates inhaled pathogens. Several cell types contribute to host defense within a complex network. The aim of this study was to evaluate the role of macrophages during pneumonia and in the regulation of the epithelial response to microorganisms.

We performed lung infection models in mice lacking myeloid RelA/p65. To study the mechanistic relationships between individual cell types, we applied co-culture models composed of airway epithelial cells (AECs) and macrophages.

Mice lacking myeloid RelA/p65 showed significantly decreased bacterial clearance, cytokine expression and neutrophil influx. In addition, the induction of epithelial keratinocyte chemoattractant expression was blunted in these animals.In vitro, AECs were largely insensitive to ligands of Toll-like receptor (TLR)2 or TLR5. Exposure to secretory products of macrophages results in an increased release of pro-inflammatory cytokines and augmented antimicrobial activity. This was associated with increased expression of TLR genes and surface expression of the proteins. Experiments with blocking antibodies showed that the effect of macrophages depends on secreted mediators, including tumour necrosis factor-α.

In conclusion, the present data show that myeloid RelA is critical for pulmonary host defense. One important mechanism is that macrophages induce the sensitivity of AEC's to microbial patterns.
TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population
Authors: Lins Tulio C , Abreu Breno S , Pereira Rinaldo W
Published: August 2009

Background

The application of a subset of single nucleotide polymorphisms, the tagSNPs, can be useful in capturing untyped SNPs information in a genomic region. TagSNP transferability from the HapMap dataset to admixed populations is of uncertain value due population structure, admixture, drift and recombination effects. In this work an empirical dataset from a Brazilian admixed sample was evaluated against the HapMap population to measure tagSNP transferability and the relative loss of variability prediction.

Methods

The transferability study was carried out using SNPs dispersed over four genomic regions: the PTPN22, HMGCR, VDR and CETP genes. Variability coverage and the prediction accuracy for tagSNPs in the selected genomic regions of HapMap phase II were computed using a prediction accuracy algorithm. Transferability of tagSNPs and relative loss of prediction were evaluated according to the difference between the Brazilian sample and the pooled and single HapMap population estimates.

Results

Each population presented different levels of prediction per gene. On average, the Brazilian (BRA) sample displayed a lower power of prediction when compared to HapMap and the pooled sample. There was a relative loss of prediction for BRA when using single HapMap populations, but a pooled HapMap dataset generated minor loss of variability prediction and lower standard deviations, except at the VDR locus at which loss was minor using CEU tagSNPs.

Conclusion

Studies that involve tagSNP selection for an admixed population should not be generally correlated with any specific HapMap population and can be better represented with a pooled dataset in most cases.
Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function
Authors: Fawaz Charbel S , Martel Philippe , Leo Damiana , Trudeau Louis-Eric
Published: August 2009

Background

Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc).

Results

DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D2autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D2autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D2receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D2autoreceptors. In addition, initial blockade of D2autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).

Conclusion

Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D2autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.
Breast, cervical, and colorectal cancer screening rates amongst female Cambodian, Somali, and Vietnamese immigrants in the USA
Authors: Samuel Ponnila S , Pringle Jane P , James Nathaniel W , Fielding Susan J , Fairfield Kathleen M
Published: August 2009

Introduction

Minority women, particularly immigrants, have lower cancer screening rates than Caucasian women, but little else is known about cancer screening among immigrant women. Our objective was to assess breast, cervical, and colorectal cancer screening rates among immigrant women from Cambodia, Somalia, and Vietnam and explore screening barriers.

Methods

We measured screening rates by systematic chart review (N = 100) and qualitatively explored screening barriers via face-to-face questionnaire (N = 15) of women aged 50–75 from Cambodia, Somalia, and Vietnam attending a general medicine clinic (Portland, Maine, USA).

Results

Chart Review– Somali women were at higher risk of being unscreened for breast, cervical, and colorectal cancer compared with Cambodian and Vietnamese women. A longer period of US residency was associated with being screened for colorectal cancer. We observed a 7% (OR 1.07, 95% CI 1.01–1.13, p = 0.01) increase in the odds that a woman would undergo a fecal occult blood test for each additional year in the US, and a 39% increase in the odds of a woman being screened by colonoscopy or flexible sigmoidoscopy for every five years of additional US residence (OR 1.39, 95% CI 1.21–1.61, p = 0.02). We did not observe statistically significant relationships between odds of being screened by mammography, clinical breast exam or papanicolaou test according to years in the US.Questionnaire– We identified several barriers to breast, cervical, and colorectal cancer screening, including discomfort with exams conducted by male physicians.

Discussion

Somali women were less likely to be screened for breast, cervical, and colorectal cancer than Cambodian and Vietnamese women in this population, and uptake of colorectal cancer screening is associated with years of residency in this country. Future efforts to improve equity in cancer screening among immigrants may require both provider and community education.
The Anabaena sensory rhodopsin transducer defines a novel superfamily of prokaryotic small-molecule binding domains
Authors: De Souza Robson F , Iyer Lakshminarayan M , Aravind L
Published: August 2009

The Anabaena sensory rhodopsin transducer (ASRT) is a small protein that has been claimed to function as a signaling molecule downstream of the cyanobacterial sensory rhodopsin. However, orthologs of ASRT have been detected in several bacteria that lack rhodopsin, raising questions about the generality of this function. Using sequence profile searches we show that ASRT defines a novel superfamily of β-sandwich fold domains. Through contextual inference based on domain architectures and predicted operons and structural analysis we present strong evidence that these domains bind small molecules, most probably sugars. We propose that the intracellular versions like ASRT probably participate as sensors that regulate a diverse range of sugar metabolism operons or even the light sensory behavior in Anabaena by binding sugars or related metabolites. We also show that one of the extracellular versions define a predicted sugar-binding structure in a novel cell-surface lipoprotein found across actinobacteria, including several pathogens such as Tropheryma, Actinomyces and Thermobifida. The analysis of this superfamily also provides new data to investigate the evolution of carbohydrate binding modes in β-sandwich domains with very different topologies.

Reviewers: This article was reviewed by M. Madan Babu and Mark A. Ragan.
Genomic profiling of breast tumours in relation to BRCAabnormalities and phenotypes
Authors: Stefansson Olafur Andri , Jonasson Jon Gunnlaugur , Johannsson Oskar Thor , Olafsdottir Kristrun , Steinarsdottir Margret , Valgeirsdottir Sigridur , Eyfjord Jorunn Erla
Published: August 2009

Introduction

Germline mutations in the BRCA1 and BRCA2 genes account for a considerable fraction of familial predisposition to breast cancer. Somatic mutations in BRCA1 and BRCA2 have not been found and the involvement of these genes in sporadic tumour development therefore remains unclear.

Methods

The study group consisted of 67 primary breast tumours with and without BRCA1 or BRCA2 abnormalities. Genomic alterations were profiled by high-resolution (~7 kbp) comparative genome hybridisation (CGH) microarrays. Tumour phenotypes were analysed by immunohistochemistry on tissue microarrays using selected biomarkers (ER, PR, HER-2, EGFR, CK5/6, CK8, CK18).

Results

Classification of genomic profiles through cluster analysis revealed four subgroups, three of which displayed high genomic instability indices (GII). Two of these GII-high subgroups were enriched with either BRCA1- or BRCA2-related tumours whereas the third was not BRCA-related. The BRCA1-related subgroup mostly displayed non-luminal phenotypes, of which basal-like were most prominent, whereas the other two genomic instability subgroups BRCA2- and GII-high-III (non-BRCA), were almost entirely of luminal phenotype. Analysis of genome architecture patterns revealed similarities between the BRCA1- and BRCA2 subgroups, with long deletions being prominent. This contrasts with the third instability subgroup, not BRCA-related, where small gains were more prominent.

Conclusions

The results suggest that BRCA1- and BRCA2-related tumours develop largely through distinct genetic pathways in terms of the regions altered while also displaying distinct phenotypes. Importantly, we show that the development of a subset of sporadic tumours is similar to that of either familial BRCA1- or BRCA2 tumours. Despite their differences, we observed clear similarities between the BRCA1- and BRCA2-related subgroups reflected in the type of genomic alterations acquired with deletions of long DNA segments being prominent. This suggests similarities in the mechanisms promoting genomic instability for BRCA1- and BRCA2-associated tumours, possibly relating to deficiency in DNA repair through homologous recombination. Indeed, this feature characterized both familial and sporadic tumours displaying BRCA1- or BRCA2-like spectrums of genomic alterations. The importance of these findings lies in the potential benefit from targeted therapy, through the use of agents leading to DNA double-strand breaks such as PARP inhibitors (olaparib) and cisplatin, for a much larger group of patients than the few BRCA1 and BRCA2 germline mutation carriers.
Methods for analyzing deep sequencing expression data: constructing the human and mouse promoterome with deepCAGE data
Authors: Balwierz Piotr J , Carninci Piero , Daub Carsten O , Kawai Jun , Hayashizaki Yoshihide , Van Belle Werner , Beisel Christian , van Nimwegen Erik
Published: August 2009

With the advent of ultra high-throughput sequencing technologies, increasingly researchers are turning to deep sequencing for gene expression studies. Here we present a set of rigorous methods for normalization, quantification of noise, and co-expression analysis of deep sequencing data. Using these methods on 122 cap analysis of gene expression (CAGE) samples of transcription start sites, we construct genome-wide 'promoteromes' in human and mouse consisting of a three-tiered hierarchy of transcription start sites, transcription start clusters, and transcription start regions.
Expression and functional characterization of four aquaporin water channels from the European eel (Anguilla anguilla)
Authors: MacIver Bryce , Cutler Christopher P. , Yin Jia , Hill Myles G. , Zeidel Mark L. , Hill Warren G.
Published: August 2009

The European eel is a euryhaline teleost which has been shown to differentially up- and downregulate aquaporin (AQP) water channels in response to changes in environmental salinity. We have characterized the transport properties of four aquaporins localized to osmoregulatory organs – gill,esophagus, intestine and kidney. By sequence comparison these four AQP orthologs resemble human AQP1 (eel AQP1), AQP3 (eel AQP3) and AQP10 (AQPe). The fourth member is a duplicate form of AQP1 (AQP1dup) thought to arise from a duplication of the teleost genome. Using heterologous expression in Xenopus oocytes we demonstrate that all four eel orthologs transport water and are mercury inhibitable. Eel AQP3 and AQPe also transport urea and glycerol, making them aquaglyceroporins. Eel AQP3 is dramatically inhibited by extracellular acidity (91% and 69% inhibition of water and glycerol transport respectively at pH 6.5) consistent with channel gating by protons. Maximal water flux of eel AQP3 occurred around pH 8.2 – close to the physiological pH of plasma in the eel. Exposure of AQP-expressing oocytes to heavy metals revealed that eel AQP3 is highly sensitive to extracellular nickel and zinc (88.3% and 86.3% inhibition, respectively) but less sensitive to copper (56.4% inhibition). Surprisingly, copper had a stimulatory effect on eel AQP1 (153.7% activity of control). Copper, nickel and zinc did not affect AQP1dup or AQPe. We establish that all four eel AQP orthologs have similar transport profiles to their human counterparts, with eel AQP3 exhibiting some differences in its sensitivity to metals. This is the first investigation of the transport properties and inhibitor sensitivity of salinity-regulated aquaporins from a euryhaline species. Our results indicate a need to further investigate the deleterious effects of metal pollutants on AQP-containing epithelial cells of the gill and gastrointestinal tract at environmentally appropriate concentrations.
Visual perception of motion in a hunting spider
Authors: Neuhofer Daniela , Machan Rudi , Schmid Axel
Published: August 2009

Like most other spiders Cupiennius salei (Keyserling 1877) has two different eye types, one pair of principal eyes and three pairs of secondary eyes. The principal eyes have two eye muscles each, which allow movement of the retina and are mainly used for the discrimination of stationary objects. The secondary eyes without such eye muscles are supposed to detect moving objects. Masking experiments were used to analyse the role of these two eye types in motion detection. In a white arena the animals were stimulated with short sequences of moving black bars. The principal eyes move involuntarily when objects are moving within the visual field of an ipsilateral secondary eye. The eye muscle activity of the principal eyes was recorded using single channel telemetry, and activity changes were taken as an indicator for the perception of motion. Masking the principal eyes with black paint and presenting a moving visual stimulus did not modify the induced muscle activity, whereas masking the secondary eyes eliminated the increase in eye muscle activity. This suggests that the secondary eyes are responsible for movement detection. We conclude that the animals are able to detect moving targets visually only with the secondary eyes. The principal eyes, by contrast, do not seem to be involved in the detection of moving targets.
Surface tension propulsion of fungal spores
Authors: Noblin Xavier , Yang Sylvia , Dumais Jacques
Published: August 2009

Most basidiomycete fungi actively eject their spores. The process begins with the condensation of a water droplet at the base of the spore. The fusion of the droplet onto the spore creates a momentum that propels the spore forward. The use of surface tension for spore ejection offers a new paradigm to perform work at small length scales. However, this mechanism of force generation remains poorly understood. To elucidate how fungal spores make effective use of surface tension, we performed a detailed mechanical analysis of the three stages of spore ejection: the transfer of energy from the drop to the spore, the work of fracture required to release the spore from its supporting structure and the kinetic energy of the spore after ejection. High-speed video imaging of spore ejection in Auricularia auriculaand Sporobolomyces yeasts revealed that drop coalescence takes place over a short distance (∼5 μm) and energy transfer is completed in less than 4 μs. Based on these observations, we developed an explicit relation for the conversion of surface energy into kinetic energy during the coalescence process. The relation was validated with a simple artificial system and shown to predict the initial spore velocity accurately (predicted velocity: 1.2 m s–1; observed velocity: 0.8 m s–1 for A. auricula). Using calibrated microcantilevers, we also demonstrate that the work required to detach the spore from the supporting sterigma represents only a small fraction of the total energy available for spore ejection. Finally, our observations of this unique discharge mechanism reveal a surprising similarity with the mechanics of jumping in animals.
Bone strength is maintained after 8 months of inactivity in hibernating golden-mantled ground squirrels, Spermophilus lateralis
Authors: Utz Jenifer C. , Nelson Stacy , O'Toole Brendan J. , van Breukelen Frank
Published: August 2009

Prolonged inactivity leads to disuse atrophy, a loss of muscle and bone mass. Hibernating mammals are inactive for 6–9 months per year but must return to full activity immediately after completing hibernation. This necessity for immediate recovery presents an intriguing conundrum, as many mammals require two to three times the period of inactivity to recover full bone strength. Therefore, if hibernators experience typical levels of bone disuse atrophy during hibernation, there would be inadequate time available to recover during the summer active season. We examined whether there were mechanical consequences as a result of the extended inactivity of hibernation. We dissected femur and tibia bones from squirrels in various stages of the annual hibernation cycle and measured the amount of force required to fracture these bones. Three groups were investigated; summer active animals were captured during the summer and immediately killed, animals in the 1 month detraining group were captured in the summer and killed following a 1-month period of restricted mobility, hibernating animals were killed after 8 months of inactivity. A three-point bend test was employed to measure the force required to break the bones. Apparent flexural strength and apparent flexural modulus (material stiffness) were calculated for femurs. There were no differences between groups for femur fracture force, tibia fracture force, or femur flexural strength. Femur flexural modulus was significantly less for the 1 month detraining group than for the hibernation and summer active groups. Thus, hibernators seem resistant to the deleterious effects of prolonged inactivity during the winter. However, they may be susceptible to immobilization-induced bone loss during the summer.
Osmoregulation and salinity tolerance in the Antarctic midge,Belgica antarctica: seawater exposure confers enhanced tolerance to freezing and dehydration
Authors: Elnitsky Michael A. , Benoit Joshua B. , Lopez-Martinez Giancarlo , Denlinger David L. , Lee Richard E.
Published: August 2009

Summer storms along the Antarctic Peninsula can cause microhabitats of the terrestrial midge Belgica antarctica to become periodically inundated with seawater from tidal spray. As microhabitats dry, larvae may be exposed to increasing concentrations of seawater. Alternatively, as a result of melting snow or following rain, larvae may be immersed in freshwater for extended periods. The present study assessed the tolerance and physiological response of B. antarctica larvae to salinity exposure, and examined the effect of seawater acclimation on their subsequent tolerance of freezing, dehydration and heat shock. Midge larvae tolerated extended exposure to hyperosmotic seawater; nearly 50% of larvae survived a 10-day exposure to 1000 mOsm kg–1 seawater and ∼25% of larvae survived 6 days in 2000 mOsm kg–1 seawater. Exposure to seawater drastically reduced larval body water content and increased hemolymph osmolality. By contrast,immersion in freshwater did not affect water content or hemolymph osmolality. Hyperosmotic seawater exposure, and the accompanying osmotic dehydration,resulted in a significant correlation between the rate of oxygen consumption and larval water content and induced the de novo synthesis and accumulation of several organic osmolytes. A 3-day exposure of larvae to hyperosmotic seawater increased freezing tolerance relative to freshwater-acclimated larvae. Even after rehydration, the freezing survival of larvae acclimated to seawater was greater than freshwater-acclimated larvae. Additionally, seawater exposure increased the subsequent tolerance of larvae to dehydration. Our results further illustrate the similarities between these related, yet distinct, forms of osmotic stress and add to the suite of physiological responses used by larvae to enhance survival in the harsh and unpredictable Antarctic environment.
Use of Nafion as a Membrane Separator in Membrane Introduction Mass Spectrometry
Authors: Gernátová Matilda , Janderka Pavel , Marcinková Andrea , Ostřížek Petr
Published: August 2009

Nafion is a commercially available perfluorosulphonate cation exchange membrane commonly used as a perm-selective separator in chlor-alkali electrolysers and as the electrolyte in solid polymer fuel cells. In our experiments, a Nafion sheet membrane serves as the interface between the aqueous sample and the vacuum in membrane introduction to the mass spectrometer (MIMS). The penetration by volatile polar compounds (VOC—methanol, ethanol, 1-propanol), volatile non-polar compounds (VOC—benzene, toluene and p-xylene), semi-volatile low polar compounds (SVOC—fluorobenzene, chlorobenzene and bromobenzene) and non-volatile polar compounds ( o-chlorophenol, m-chlorophenol and p-chlorophenol) in aqueous solution through the Nafion membrane to the mass spectrometer was studied. In all cases, a simple fragmentation pattern of the intact molecule was observed, typically with m/z = nominal mass + 1 as the most intensive ion current, which suggests that the ionisation process takes part in which water acts as the chemical ionisation reagent. No additional gases were needed for chemical ionisation. We also measured detection limits and linear dynamic ranges of all observed compounds with Nafion membrane MIMS. The observed detection limits were in the order of ppb for the alcohol and aromatic groups and for the halogenbenzene and monochlorophenol groups they were in the order of ppm. Linear dynamic ranges for all tested compounds were one order of magnitude.
Ionization of 4,4′-Bis(Phenylethynyl)-Anthracene by Electron Impact
Authors: Kukhta Alexander V. , Kukhta Iryna N. , Zavilopulo Anatoly N. , Agafonova Anna S. , Shpenik Otto B.
Published: August 2009

Ionization of a 4,4′-bis(phenylethynyl)anthracene (C30H18, BPEA) molecule is studied for the first time at different energies of bombarding electrons in crossed electron and molecular beams. The relative cross-section of single ionization of a BPEA molecule in the energy range of 5–55 eV is measured. The ionization potential, Ei = 7.62 ± 0.2 eV, is determined using the threshold region of C30H18+ ion yield energy dependence. A scheme of the BPEA molecule fragmentation is proposed. Experimental results are in reasonable accordance with calculations made in the framework of the density functional theory.
Structural Characterization of Nitrated 2′-Hydroxychalcones by Electrospray Ionization Tandem Mass Spectrometry
Authors: Barros Ana I.R.N.A. , Nunes Fernando M. , Barros Cristina , Silva Artur M.S. , Domingues M. Rosário M.
Published: August 2009

Isomeric 2′-hydroxychalcones bearing nitro and methoxy groups in different positions of their skeleton were analyzed by tandem mass spectrometry (MS/MS) with electrospray ionization (ESI), in positive mode. Collision-induced dissociation of the protonated molecules, [M + H]+, formed under electrospray conditions were studied and it was found that the product ion spectra of these chalcones presented different fragmentation patterns depending on the position of the substituents on the molecule. The product ion spectra (ESI-MS/MS) of the B ring ortho-nitro substituted 2′-hydroxychalcone and of the 4′-methoxychalcones showed loss of OH•, 2OH• and combined losses of OH• and H2O. These fragment ions were absent in the spectra of the respective meta- and para isomers. The observed differences in the product ion spectra of these nitrochalcones allowed identification of the o-nitro derivatives. Distinction between the meta- and para-derivatives was not achieved. Chalcones bearing 6′-methoxy substituents showed distinct fragmentation from the one observed for their isomers, 4′-methoxychalcones, since they present only one fragment ion, a typical (0,αA – H)+ and, therefore, do not allow detailed structural information to be obtained, nor to differentiate between the o-, m- or p-nitro isomers. Overall, it was found that small changes in the substitution pattern of chalcones change their fragmentation considerably in the ESI-MS/MS, and that these features permit the differentiation of specific isomers of these 2′-hydroxynitrochalcones.
Probing the Mechanism of Action of Potential Anticancer Agents at a Molecular Level Using Electrospray Ionisation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
Authors: Tietze Lutz F. , Krewer Birgit , Frauendorf Holm
Published: August 2009

Treating cancer without harming healthy tissue is an important goal in modern medicine. Our research group has developed a series of novel, relatively non-toxic glycosidic prodrugs that are activated to give the corresponding highly cytotoxic drugs selectively in the tumour tissue. Our first investigations have shown a high duplex DNA alkylation efficiency of the drugs, whereas the prodrugs showed almost no tendency for alkylation of duplex DNA. Herein we report on novel investigations of the mode of action of the anti-cancer drugs on a molecular level. Using high-resolution mass spectrometry, we determined the reactivity of these drugs as well as of other drugs of similar structure against different nucleophiles such as RNA and the tripeptide glutathione. In addition, the new drugs were also tested for their interaction with duplex DNA. All compounds show a high reactivity against duplex DNA, whereas the alkylation efficiency regarding RNA and glutathione is only poor. Furthermore, the alkylation of duplex DNA correlates qualitatively but not quantitatively with the cytotoxicity of the drugs. Consequently, other factors besides the alkylation efficiency such as the stability of the drugs seem to influence their biological activity. Altogether the results show that high-resolution mass spectrometry constitutes a powerful method for studying the mode of action of drugs on a molecular level.
“Soft” or “Hard” Ionisation? Investigation of Metastable Gas Temperature Effect on Direct Analysis in Real-Time Analysis of Voriconazole
Authors: Lapthorn Cris , Pullen Frank
Published: August 2009

The performance of the direct analysis in real-time (DART) technique was evaluated across a range of metastable gas temperatures for a pharmaceutical compound, Voriconazole, in order to investigate the effect of metastable gas temperature on molecular ion intensity and fragmentation. The DART source has been used to analyse a range of analytes and from a range of matrices including drugs in solid tablet form and preparations,1–3 active ingredients in ointment,1 naturally occurring plant alkaloids,1 flavours and fragrances,4 from thin layer chromatography (TLC) plates,5,6 melting point tubes and biological matrices including hair, urine7 and blood. The advantages of this technique include rapid analysis time (as little as 5 s), a reduction in sample preparation requirements, elimination of mobile phase requirement and analysis of samples not typically amenable to atmospheric pressure ionisation (API) techniques. This technology has therefore been proposed as an everyday tool for identification of components in crude organic reaction mixtures.
Three new, quick CEC methods for determining the amounts of exchangeable calcium cations in calcareous clays
Authors: Dohrmann R. , Kaufhold S.
Published: August 2009

The cation exchange capacity (CEC) is one of the most important properties of clays in terms of their performance in both natural and technical processes. For decades, common methods for determining exchangeable cations have failed when calcareous clays or soils were examined, because calcite is at least partly dissolved throughout the exchange experiment which in turn increases measureable Ca2+ concentrations. As a result, exchangeable Ca2+ and the sum of exchangeable cations by far exceed the amount of negative charges. In the past, the silver-thiourea method (AgTU) has been modified to overcome this problem (AgTUcalcite), but is unsatisfactory as the method is laborious. In the present study three new methods based on two alternative metal complexes, cobalt(III) hexamine (CoHex) and copper(II) triethylenetetramine (Cu-trien), are proposed. The optimum solid/liquid ratios of these methods and the optimum complex concentration of Cu-trien are reported, depending on the mineralogical composition of the samples. The key development is that the exchange solutions are saturated with respect to calcite prior to the experiment. Approximately 70–90% of the dissolution of calcite present as an admixture in a clay sample is suppressed in the subsequent cation exchange experiment, but not all. The Ca2+ exchange is not suppressed and there is no evidence for any precipitation of this Ca2+. Three possibilities for how to handle this problem are discussed, one of which is to perform no further correction. The resulting error arises from the remaining calcite solubility of the different solutions after pre-treatment with calcite. This corresponds to errors of 0.2–1.3 (CoHexcalcite)and 0.7–8.4 (Cu-triencalcite) meq/100 gCa2+ for samples with small and large CEC values, respectively. As a consequence of the poor performance of Cu-triencalcite for samples with large CEC, a more concentrated Cu-trien5 × calcite solution was developed which performed much better: 0.1–0.8 meq/100 g(Cu-trien5 × calcite). For Cu-trien5 × calcite and CoHexcalcite at least, the errors are in the range of the non-systematic scattering for exchangeable Ca2+ determination. Therefore, the methods suggested provide ‘operationally correct’ Ca2+ values without additional effort. Moreover, owing to the high selectivity of the index cations applied in the present study, only one exchange step is required, providing a significant advantage over the AgTUcalcite method.
Factors governing the formation of lithiophorite at atmospheric pressure
Authors: Cui Haojie , You Lei , Feng Xionghan , Tan Wenfeng , Qiu Guohong , Liu Fan
Published: August 2009

Lithiophorite is a naturally occurring Mn oxide mineral commonly found in soils and sediments. The usual method of synthesizing lithiophorite is via a hydrothermal process in an autoclave at relatively high temperature and pressure. In the present study, an alternative, reflux method, at atmospheric pressure, for synthesis of lithiophorite was developed successfully. The influence of reaction duration, temperature, type of precursor birnessite (H-birnessite, Na-birnessite, aged Na-birnessite), and pH on the formation of lithiophorite were investigated by reflux treatment of lithium-aluminum hydroxide complex ion (

)-exchanged birnessite. The results show that the degree of conversion of lithiophorite decreases with decreasing reaction temperature. Lithiophorite can be obtained at pH values from 5.0 to 9.0, but a circumneutral pH is more favorable for formation at atmospheric pressure. Conversion of Na-birnessite (Bir-OH) to lithiophorite is more favored than aged Na-birnessite (Bir-OH-A). Lithiophorite was not obtained by refluxing the

ion-exchanged H-birnessite (Bir-H) sample. The rate of conversion of lithiophorite increases with increasing reflux time. Lithiophorite synthesized by a reflux process has pseudo-hexagonal crystals of 0.1–0.5 µm with a chemical composition of Li0.24Al0.46MnO2.67(H2O)1.25. The results have important implications for the origin and underlying mechanism of lithiophorite formation in the environment.
Surface properties of illite-smectite minerals as detected by interactions with rhodamine 6G dye
Authors: Šucha V. , Czímerová A. , Bujdák J.
Published: August 2009

Interactions between smectite clay minerals and various organic dyes have been studied extensively, but little information has accumulated from dye interactions with mixed-layer illite-smectite (I-S) minerals, especially regarding relationships with clay layer expandability, layer charge, particle size/shape, and molecular aggregation of organic dye molecules. The purpose of this study was to investigate the surface interactions of a set of mixed-layer illite-smectites from different geological environments with Rhodamine 6G dye. The samples used have different amounts of expandable smectite interlayers, different particle size and/or shape, and different layer-charge density at the surface. Five smectites with differences in layer charge and some non-expandable layer silicates were also tested. The interactions detected by UV-vis spectroscopy show no reaction between R6G and non-expandable minerals (kaolinite, mica), and intense reactions forming H-aggregates and monomers with smectites and illite-smectites. The intensity of H-aggregate formation increases with increase in the layer charge of smectites. Mixed-layer illite-smectites interact with R6G more intensely than do smectites. H-aggregate and monomer formation increases with the illitization process for randomly ordered illite-smectites (R = 0) and decreases in the course of illitization for the ordered illite-smectites (R > 0).
Near-infrared spectroscopic analysis of acid-treated organo-clays
Authors: Madejová Jana , Pálková Helena , Pentrák Martin , Komadel Peter
Published: August 2009

The potential use of near-infrared (NIR) spectroscopy as a characterization tool for organo-clays would be a great asset but little work has been done in this regard because the application of NIR to clay mineral studies is a relatively new phenomenon. The purpose of this study was to use NIR spectroscopy to investigate the effect of alkylammonium cations on the acid dissolution of a high-charge montmorillonite (SAz-1). Detailed analysis of the spectra of Li+-, TMA+- (tetramethylammonium), and HDTMA+- (hexadecyltrimethylammonium) saturated SAz-1 montmorillonite in the NIR region was achieved by comparing the first overtone (2ν) and combination (ν+δ) bands of XH groups (X = O, C) with the fundamental stretching (ν) and bending (δ) vibrations observed in the mid-infrared (MIR) region. Comprehensive analysis of the vibrational modes of CH3-N, CH3-C, and -CH2-C groups of TMA+ and HDTMA+ cations detected in the MIR and NIR regions was also performed. Both MIR and NIR spectra demonstrated that exchange of Li+ by TMA+ only slightly improved the resistance of SAz-1 layers to dissolution in 6 M HCl at 80°C, while exchange by the larger HDTMA+ cations almost completely protected the montmorillonite layers from acid attack. Use of NIR spectra in reaching these conclusions was crucial. Only in the NIR region could the creation of SiOH groups be monitored, which is an important indicator of the acidification of the montmorillonite surface. The OH-overtone region in the spectra of Li-SAz-1 and TMA-SAz-1 revealed that the SiOH band near 7315 cm−1 increases in intensity with enhanced acid treatment. In contrast, no SiOH groups were identified in the NIR spectra of HDTMA-SAz-1 treated in HCl, indicating that HDTMA+ completely covers the inner and outer surfaces of the montmorillonite and hinders access ofprotons to the Si-O− bonds created upon acid treatment.
Pediatric Brain Natriuretic Peptide Concentrations Vary with Age and Sex and Appear to Be Modulated by Testosterone
Authors: Saenger Amy K , Dalenberg Daniel A , Bryant Sandra C , Grebe Stefan K , Jaffe Allan S
Published: August 2009

Background: Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study.

Methods: We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone–binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone.

Results: Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex.

Conclusions: In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .
Religion und Gefühl. Religionspsychologische Aspekte im Anschluss an William James
Authors: Weyel Birgit
Published: August 2009

On the threshold of modernity, religion and feelings have entered into a close relationship in Protestantism. In Reden über die Religion (1799) Friedrich Schleiermacher defined religion as feelings, indicating an original form of experience. Religion is thereby an existential seizure by a supernatural revelation that is, nevertheless, individually determined. From a religious-psychological perspective, William James established in The Varieties of Religious Experience (1902) that a close connection exists between religion and feelings. These can be described as religious feelings or as religion, whereby symbols which are defined in religious terms can be used for interpreting feelings and the individual acquires a frame of reference for interpreting.
Quentin Crisp und die Kunst der Schamlosigkeit
Authors: Hotz-Davies Ingrid
Published: August 2009

Gender and sexuality belong to social markers that are most heavily influenced and also enforced by the affect of shame and the interpellation of subjects as shameful. Quentin Crisp's The Naked Civil Servant (1968) shows that discussions of shame and gender/sexuality are incomplete if they do not take into account strategies of “disinterpellation” (Sedgwick), which seek to undo the mechanisms of shame and shaming through displays of shamelessness.
Zwischen Leidenschaft und Disziplinierung. “Treue” als gefühlspolitischer Kampfbegriff in der neueren deutschen Geschichte
Authors: Buschmann Nikolaus
Published: August 2009

Modernisation theories consider allegiances based on personal loyalty between rulers and subjects as expressions of a more “traditional” understanding of state and society. Nevertheless, such notions have proved to be remarkably persistent in the modern political imagination. Constitutional states may now legitimate political rule, but “systems of loyalty” (Paolo Prodi) have continued to mobilise political and military allegiances well into the twentieth century. This is particularly true for the concept of “Treue”, which has played a key role in the construction of German national identity in modern times.
Die Lehre der Affekte und ihre Rolle im Werk Dostoevskijs
Authors: Lachmann Renate
Published: August 2009

The rhetorical doctrine of affects has not only developed a catalogue of emotions but has also described strategies to produce emotions and it has organized them into different stylistic types. Emotional symptoms are linked to rhetorical rules, aiming at the representation and production of passions. Rhetorical and poetic treatises have preserved the memories of these emotional techniques, and every period in history has its own ideas about exhibiting or suppressing emotional outbursts, highlighting either the Aristotelian or the Stoic tradition. Dostoevsky's work combines a modernized version of the rhetoric of affects with a psychosomatic discourse on hysteria and epilepsy. Hysteria appears in his novels as a special form of representation rather than as a psychic illness. Hysteria redefined as a stylistic means, combines illness with rhetoric in such a way that both refer to each other.
Indifferenz oder: Prothesen des Gefühls. Bemerkungen zur Variation einer männlichen Emotion
Authors: Kimmich Dorothee
Published: August 2009

Historically, indifference and disinterest belong to a variable semantic field of anti-feeling. This anti-feeling is predominantly gendered as male, and linked to a “self-fashioning of coolness”. Philosophical traditions of indifference go back to Hellenistic sources and range from Nietzsche's cynicism, over Plessner's cool persona, to Sloterdijk's “Kynismus”. They concern themselves with technologies of the self and stress disinterest as a strategy of survival. In the 1920s in Germany, Helmuth Plessner, Georg Simmel and Ernst Jünger argued that modern life in urban and capitalist environments generate emotional coolness; they foreground things and surfaces, yielding a poetics of “Sachlichkeit”. According to Jünger, war and the military form an attractive background for the concept of indifference. Joseph Roth and Erich Kästner play in their novels with the aesthetic possibilities of nearness and distance. Unable to live truly, their protagonists are forced to observe life from a distance. Albert Camus and Michel Houellebecq adopt this tradition of indifference, linking their disinterested heroes with moral monstrosities and perversions.
Television program avoidance and personality
Authors: Böcking Tabea , Fahr Andreas
Published: August 2009

Recent communication research indicates that approach and avoidance constitute two separate yet co-existing processes during media exposure. While many studies address TV approach behavior, little is known about TV avoidance behavior. Furthermore, personality has yet to be linked to avoidance behavior. This study analyzes the influence of personality on TV program avoidance. Data show that the “Big Five” personality characteristics (Neuroticism, Extraversion, Openness, Conscientiousness, Agreeableness) and Risk and Fight Willingness influence program avoidance, albeit to varying degrees. While the specific correlations are discussed in the paper, the results generally reveal that the combination of personality and avoidance has added value in terms of understanding of TV using behavior compared to the frequently analyzed link between personality and approach. For nearly all personality characteristics, data show that the avoidance perspective is more than the inversion of the approach perspective. The findings are discussed with reference to gratification and selectivity research.
Dickens and the Wolf Man: Childhood Memory and Fantasy inDavid Copperfield
Authors: Lougy Robert E.
Published: August 2009

This essay draws on Freud's case history of the Wolf Man (From the History of an Infantile Neurosis; 1918), which presents one of the most famous dreams in the history of psychoanalysis, in order to consider a moment inDavid Copperfield(1850) that constitutes the earliest childhood memory in Dickens's fiction. These two moments in Freud and Dickens occupy problematic sites that seem to slide between fantasy on the one hand and dreams on the other, and an examination of them helps open up the question of how texts remember—or fantasize—childhood and its power to structure adult experience.