julilili42/papers huggingface dataset:
Observing Proteins as Single Molecules Encapsulated in Surface‐Tethered Polymeric Nanocontainers
2009-02-03

Abstract Protein unfolding inside immobilized polymerosomes : One of the most interesting properties of polymeric vesicles is their remarkable stability against extreme temperatures and osmotic stress, and their longevity even under harsh environmental conditions. We have demonstrated, in an application on protein folding, that surface‐tethered polymerosomes are suitable for performing time‐resolved single molecule studies with encapsulated proteins, as illustrated here. magnified image Immobilizing biomolecules provides the advantage of observing them individually for extended time periods, which is impossible to accomplish for freely diffusing molecules in solution. In order to immobilize individual protein molecules, we encapsulated them in polymeric vesicles made of amphiphilic triblock copolymers and tethered the vesicles to a cover slide surface. A major goal of this study is to investigate polymeric vesicles with respect to their suitability for protein‐folding studies. The fact that polymeric vesicles possess an extreme stability under various chemical conditions is supported by our observation that harsh unfolding conditions do not perturb the structural integrity of the vesicles. Moreover, polymerosomes prove to be permeable to GdnHCl and, thereby, ideally suited for unfolding and refolding studies with encapsulated proteins. We demonstrate this with encapsulated phosphoglycerate kinase, which was fluorescently labeled with Atto655, a dye that exhibits pronounced photoinduced electron transfer (PET) to a nearby tryptophan residue in the native state. Under unfolding conditions, PET was reduced, and we monitored alternating unfolding and refolding conditions for individual encapsulated proteins.
The placebo response in functional dyspepsia – reanalysis of trial data
2009-02-03

Abstract Clinical trial data rarely identify factors contributing to the placebo response. We reanalysed the data from the placebo arm ( n = 157) of a functional dyspepsia (FD) trial to determine predictors of placebo response including total GIS score, change in GIS score during run‐in, type of FD symptoms, duration of illness, age, gender, body mass index (BMI), family occurrence of FD‐like symptoms, smoking and alcohol consumption. The same response criteria were applied to the drug arm ( n = 158) of the study. Based on the initial 40% response criterion of the study, 35 (22.2%) were classified as placebo responders (PR), whilst 122 (78.8%) were placebo non‐responders (PnR). Response rates for the drug arm were 41.1 and 56.9% respectively. PR had significantly lower GIS scores compared to PnR at visit 1 (10.6 ± 0.6 and 12.3 ± 0.4, respectively, P = 0.035), but not at visit 2 with study medication dispensing (10.9 ± 0.5 and 11.3 ± 0.4). Hence, PR symptoms increased during run‐in by 4.2% whilst PnR symptoms decreased by 6.3% ( P &lt; 0.005). Gender, age and duration and type of FD symptoms were not different between PR and PnR. Smoking was less prevalent in PR (3%) compared to PnR (21%) ( P &lt; 0.025). Increasing the criteria for the placebo response resulted in higher BMI for PR than for PnR ( P = 0.035). None of the predictors for placebo response were able to distinguish responders from non‐responders to the drug. Variables predicting the PR point towards behavioural and biological mechanism of the PR, operating simultaneously and independently.
Cerebrospinal fluid and interstitial fluid volume measurements in the human brain at 3T with EPI
2009-02-03

Abstract Cerebrospinal fluid (CSF) diffusion into periventricular white matter is one of the pathophysiological features of hydrocephalus of any kind. In standard clinical routine periventricular hyperintensities, size of the ventricular system, and invasive CSF pressure measurement are the key diagnostic methods. Recently a method called quantitative blood oxygenation level‐dependent (qBOLD) was proposed by He and Yablonskiy (Magn Reson Med 2007;57:115–126), which uses the signal evolution of a GESSE sequence to extract quantitative information about hemodynamic parameters. In this study a similar method was used to extract volume fraction information of CSF and interstitial fluid (ISF) in the human brain. A standard gradient recalled echo / echo planar imaging (GRE‐EPI) sequence with variable echo time was used for the acquisition of the MRI signal. A first test on healthy subjects yielded consistent results for ISF/CSF volume fraction, which were in good agreement with results found in the literature. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Direct Determination of the Enantiomeric Purity or Enantiomeric Composition of Methylpropionates Using a Single Capacitive Microsensor
2009-02-03

Capacitive enantioselective sensors have been demonstrated to provide antipodal signals upon dosage of, e.g., the enantiomers of methyl lactate or methyl-2-chloropropionate. In a next step, these sensors have been used to not only qualitatively determine the nature of the respective enantiomer or to quantitatively measure its concentration upon dosage in the pure form but to also assess the enantiomeric composition of mixtures by using only a single capacitive-type sensor. The enantioselective coating material consisted of a modified gamma-cyclodextrin. It was shown that the absorption and desorption kinetics of the two enantiomers of, e.g., the methyl-2-chloropropionate, are sufficiently different and produce sensor signal features that enable an accurate determination of the enantiomeric purity and composition of the chiral analyte or mixture under investigation. The method even allows for detecting small impurities in commercially available samples labeled as 99% enantiomerically pure. Moreover, the results disclosed here show that sensor techniques can be used to reveal details of enantioselective analyte-receptor and analyte-matrix interactions.
4-[2-(4-Fluorophenyl)furan-3-yl]pyridine
2009-02-03

In the crystal structure of the title compound, C(15)H(10)FNO, the furan ring makes dihedral angles of 40.04 (11) and 25.71 (11)° with the pyridine and 4-fluoro-phenyl rings, respectively. The pyridine ring makes a dihedral angle of 49.51 (10)° with the 4-fluoro-phenyl ring. Non-conventional C-H⋯F and C-H⋯N hydrogen bonds are effective in the stabilization of the crystal structure.
4-[2-(4-Fluorophenyl)-1H-pyrrol-3-yl]pyridine
2009-02-03

In the crystal structure of the title compound, C(15)H(11)FN(2), the pyrrole ring makes dihedral angles of 33.19 (9) and 36.33 (10)° with the pyridine and 4-fluoro-phenyl rings, respectively. The pyridine ring makes a dihedral angle of 46.59 (9)° with the 4-fluoro-phenyl ring. In the crystal structure, an N-H⋯N hydrogen bond joins the mol-ecules into chains.
Adhesion‐Related Complications Are Common, But Rarely Discussed in Preoperative Consent: A Multicenter Study
2009-02-04

Abstract Background Peritoneal adhesions are recognized as an important cause for patient morbidity, but complications related to adhesions occur relatively late after the original operation. Therefore preoperative consent may not adequately reflect the proportions of the problem. Methods A total of 200 patients admitted for intraperitoneal operations at six hospitals were prospectively reviewed to identify whether adhesion‐related complications were documented as possible adverse events in their respective consent forms. Results Adhesion‐related complications were documented in 8.5% ( n = 17) of consent forms (bowel obstruction n = 8, requirement for further operations n = 5, difficult reoperation n = 1, pain n = 3). A direct relationship with adhesions was noted in n = 9 of these consent forms. Conclusions Preoperative informed consent does not adequately reflect the magnitude of adhesion‐related problems. These findings have immediate implications for clinical practice.
Single-molecule spectral dynamics at room temperature
2009-02-04

Abstract Single-molecule techniques have attracted much attention over the past decade as they represent the ultimate limit of detection and sensitivity for the molecular sciences. Moreover, these studies benefit from the fact that averaging over a huge number of species inherent in every ensemble study is overcome by single-molecule methods. A single emitter in its individual nano-environment can be observed and its specific response can be studied, for example, by fluorescence spectroscopy. The temporal evolution and spectral distribution of the fluorescence reveals molecular emission dynamics. Fluctuations of extrinsic and intrinsic nature can be discriminated and, for example, conformational changes of the molecular structure or the spectral influence of the flexibility of the molecular environment can be studied. In addition to fluorescence-based methods, surface-enhanced Raman scattering has developed into a powerful tool with single-molecule sensitivity, providing direct insight into the molecular structure of the target system. The careful analysis of the observed spectral fluctuations can provide information on the Raman enhancement process experienced by a molecule adjacent to a noble metal particle. Keywords: single molecule spectroscopySERSfluorescenceautofluorescent proteinsspectral fluctuation Acknowledgement This project was partly funded by the Deutsche Forschungsgemeinschaft (Me 1600/4-1).
Biochemical and physiological characterization of Arabidopsis thaliana AtCoAse: a Nudix CoA hydrolyzing protein that improves plant development
2009-02-04

CoA is required for many synthetic and degradative reactions in intermediary metabolism and is the principal acyl carrier in prokaryotic and eukaryotic cells. CoA is synthesized in five steps from pantothenate, and recently, the CoA biosynthetic genes of Arabidopsis have all been identified and characterized. Here, we demonstrate the biochemical and physiological characterization of a pyrophosphatase from Arabidopsis thaliana , called AtCoAse (locus tag At5g45940), cleaving CoA to 4′‐phosphopantetheine and 3′,5′‐adenosine‐diphosphate in the presence of Mg 2+ /Mn 2+ ions. The CoA cleaving enzyme is a member of the Nudix hydrolases, pyrophosphatases that hydrolyze nucleoside diphosphates, already described as CoAse and now further characterized in detail by us. Mutagenesis of residues of the so‐called Nudix and NuCoA motifs drastically reduced the hydrolase activity. AtCoAse is not absolute specific for CoA, and in the presence of Mn 2+ ions, a minor hydrolyzing activity was observed with NADH as substrate. The AtCoAse expression is ubiquitous, strongly in flower and unaffected by abiotic stress. The immunohistochemical localization indicates that the AtCoAse protein is observed in the cytoplasm of distinct cells types from different heterotrophic Arabidopsis tissues, mainly restricted to the vascular elements of the root and shoot and in flower and developing embryo. Transgenic Arabidopsis plants, with increased AtCoAse expression, show altered growth rates and development, expanding their live cycle far away from the wild‐type.
Virtual Observatory studies of Planetary Nebulae
2009-02-05

Starting from the Strasbourg ESO Catalogue (SEC) of Planetary Nebulae (PNe), the largest PNe compilation available with ~ 1500 objects, we undertook a comprehensive study of the whole PN population, never carried out so far, only using on-line catalogues and data from public imaging surveys. The study includes the PN dynamics through their measured proper motions (PMs), the study of their galactocentric orbits, the study of their interactions with the interstellar medium (ISM), and the study of their UV-to-IR spectral energy distribution (SED). As a preliminary step required to perform cross-correlations with on-line catalogues, we first went through a systematic reassessment of the PN coordinates (Kerber et al. 2003a).
Quarks in Coulomb gauge perturbation theory
2009-02-06

Coulomb gauge quantum chromodynamics within the first order functional formalism is considered. The quark contributions to the Dyson-Schwinger equations are derived and one-loop perturbative results for the two-point functions are presented.
Polarized Spectroscopy Studies of Single Molecules of Porphycenes: Tautomerism and Orientation
2009-02-10

Using ambient atmosphere instead of pure nitrogen environment enabled efficient recording of room temperature fluorescence from single molecules of porphycenes, chromophores with a high triplet formation efficiency. Double hydrogen transfer between two chemically identical trans tautomers has been demonstrated for parent porphycene and three alkyl derivatives by the analysis of spatial patterns of the emission obtained after raster scanning the sample excited with an appropriately polarized laser beam. Because of tautomerization, fluorescence in porphycenes is due to two nearly orthogonal transition dipole moments. This property allows the spatial orientation of the single molecule chromophores to be determined using radially and azimuthally polarized laser beams as excitation sources. 1.
Low concentration of ziprasidone in human milk: a case report
2009-02-10

Although second-generation antipsychotics are established as the first-line treatment for schizophrenia, female patients are often excluded from this efficient treatment for safety reasons in pregnancy or whilst breastfeeding. For this reason, research on this subject mostly relies on case reports, although there is a great need to establish modern guidelines for treatment. Milk-to-plasma (M:P) ratios have been reported for clozapine (2.79–4.32; Winans, 2001), olanzapine (0.10–0.84; Gardiner et al. 2003), risperidone/9-OH risperidone (0.10–0.42/0.24–0.50; Gentile, 2004) and aripiprazole (0.18–0.20; Schlotterbeck et al. 2007). According to one case report, the infant ingests 0.09–0.43% of the weight-adjusted maternal dose of quetiapine (Lee et al. 2004). To our knowledge, this is the first report of ziprasidone in human breast milk. Mrs B, a 22-yr old woman (gravida I, para I) was admitted to our psychiatric hospital 7 d after giving birth to a healthy boy. She had not reported her psychiatric history to her gynaecologists, who were not aware that the patient had been diagnosed with schizophrenia. On showing peripartum agitation, anxiety and verbal aggression, the ...
Adenovirus‐mediated cytosine deaminase/5‐fluorocytosine suicide gene therapy of human hepatoblastoma in vitro
2009-02-11

Abstract Background Multidrug resistance is a key factor for the sobering outcome of relapsed and metastatic human hepatoblastoma (HB). Gene directed treatment approaches were recently identified as possible treatment options against advanced HB, in which standard chemotherapy regimens are partially insufficient. The aim of this study was to systematically analyze the effects of suicide gene therapy in three HB cell lines using a yeast‐derived cytosine deaminase (YCD)‐combined yeast uracil phosphoribosyltransferase (YUPRT)‐based adenovirus‐mediated gene transfer. Procedure YCD and YUPRT were fused to form the bifunctional suicide gene SuperCD. Adeonoviral vectors were used for transduction. Tumor cells transduced at MOI 50 were incubated with 5‐fluorocytosine (5‐FC) in ascending concentrations. Results Transduction rates were 87.8% (+6.7) in the mixed HB cell line HUH6, 98.6% (+1.4) in the epithelial HB cell line HepT1 and 93.6% (+0.6) in the multifocal HB embryonal cell line HepT3, respectively. In HepT3 and HepT1 cells suicide gene therapy with SuperCD/5‐FC was highly effective leading to HB cell damage far above those of application of the prodrug 5‐FC only. In HUH6 cells the approach had no effect due to a lack in activity of the CMV promoter being employed for transcription of the SuperCD transgene. Conclusion Assuming employment of fully active promoters, the SuperCD/5‐FC approach may serve as a potentially useful anti‐tumor strategy against advanced HB. Pediatr Blood Cancer 2009;53:145–151. © 2009 Wiley‐Liss, Inc.
RAN Is Not a Measure of Orthographic Processing. Evidence From the Asymmetric German Orthography
2009-02-12

Abstract In three large samples (N = 1248) of children learning to read German we investigated the correlations between rapid automatized naming (RAN), phonological awareness (PA), phonological decoding (nonword reading fluency), and orthographic processing (word reading fluency and spelling). In a series of hierarchical regression analyses, RAN explained more variance in word and nonword reading fluency than PA, whereas PA explained more variance in spelling than RAN. This pattern was confirmed when PA response times were assessed instead of response accuracy. Two further regression models challenge the view that the RAN-literacy association is mediated by orthographic processing. First, RAN accounts for unique variance in word reading fluency even when differences in orthographic spelling were introduced before RAN. Second, RAN accounts for hardly any variance in word reading fluency when introduced after nonword reading fluency.
Linear-scaling atomic orbital-based second-order Møller–Plesset perturbation theory by rigorous integral screening criteria
2009-02-12

A Laplace-transformed second-order Møller–Plesset perturbation theory (MP2) method is presented, which allows to achieve linear scaling of the computational effort with molecular size for electronically local structures. Also for systems with a delocalized electronic structure, a cubic or even quadratic scaling behavior is achieved. Numerically significant contributions to the atomic orbital (AO)-MP2 energy are preselected using the so-called multipole-based integral estimates (MBIE) introduced earlier by us [J. Chem. Phys. 123, 184102 (2005)]. Since MBIE provides rigorous upper bounds, numerical accuracy is fully controlled and the exact MP2 result is attained. While the choice of thresholds for a specific accuracy is only weakly dependent upon the molecular system, our AO-MP2 scheme offers the possibility for incremental thresholding: for only little additional computational expense, the numerical accuracy can be systematically converged. We illustrate this dependence upon numerical thresholds for the calculation of intermolecular interaction energies for the S22 test set. The efficiency and accuracy of our AO-MP2 method is demonstrated for linear alkanes, stacked DNA base pairs, and carbon nanotubes: e.g., for DNA systems the crossover toward conventional MP2 schemes occurs between one and two base pairs. In this way, it is for the first time possible to compute wave function-based correlation energies for systems containing more than 1000 atoms with 10 000 basis functions as illustrated for a 16 base pair DNA system on a single-core computer, where no empirical restrictions are introduced and numerical accuracy is fully preserved.
The influence of baseline symptoms and insight on the therapeutic alliance early in the treatment of schizophrenia
2009-02-12

Abstract Background The consistent association between therapeutic alliance and outcome underlines the importance of identifying factors which predict the development of a positive alliance. However, only few studies have examined the association between pretreatment characteristics and alliance formation in patients with schizophrenia. Objective The study examined whether symptoms and insight would predict the therapeutic alliance in psychotherapy of schizophrenia. Further, the associations and differences between patient and therapist alliance ratings were studied. Methods Eighty patients with schizophrenia spectrum disorders received manual-based psychotherapy. Assessment of symptoms and insight was conducted at baseline, and questionnaire-based alliance ratings were obtained three weeks into treatment. Patient and therapist alliance ratings were examined separately. Results Patient and therapist alliance ratings were not significantly correlated ( r = 0.17). Patient ratings of the alliance were significantly higher than the ratings of their therapists ( d = 0.73). More insight in psychosis significantly predicted higher patient ratings of the alliance. Less positive and negative symptoms were significant predictors of higher therapist alliance ratings. Conclusion The findings indicate that symptoms and insight have an influence on the therapeutic alliance in the treatment of schizophrenia spectrum disorders. Patients' and therapists' perceptions of the alliance do not seem to demonstrate much convergence.
Fluorescence intensity, lifetime, and anisotropy screening of living cells based on total internal reflection techniques
2009-02-12

A setup for fluorescence measurements of surfaces of biological samples, in particular the plasma membrane of living cells, is described. The method is based on splitting of a laser beam and multiple total internal reflections (TIR) within the bottom of a microtiter plate, such that up to 96 individual samples are illuminated simultaneously by an evanescent electromagnetic field. Two different screening procedures for the detection of fluorescence arising from the plasma membrane of living cells by High Throughput Screening (HTS) and High Content Screening (HCS), are distinguished. In the first case a rapid measurement of large sample numbers based on fluorescence intensity, and in the second case a high content of information from a single sample based on the parameters fluorescence lifetime (Fluorescence Lifetime Screening, FLiS) and fluorescence anisotropy (Fluorescence Lifetime Polarization Screening, FLiPS) is achieved. Both screening systems were validated using cultivated cells incubated with different fluorescent markers (e. g. NBD-cholesterol) as well as stably transfected cells expressing a fluorescent membrane-associating protein. In addition, particularly with regard of potential pharmaceutical applications, the kinetics of the intracellular translocation of a fluorescent protein kinase c fusion protein upon stimulation of the cells was determined. Further, a caspase sensor based on Förster Resonance Energy Transfer (FRET) between fluorescent proteins was tested. Enhanced cyan fluorescent protein (ECFP) anchored to the inner leaflet of the plasma membrane of living cells transfers its excitation energy via a spacer (DEVD) to an enhanced yellow fluorescent protein (EYFP). Upon apoptosis DEVD is cleaved, and energy transfer is disrupted, as proven by changes in fluorescence intensity and decay times.
Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder
2009-02-13

The large‐conductance, voltage‐dependent and Ca 2+ ‐dependent K + (BK) channel links membrane depolarization and local increases in cytosolic free Ca 2+ to hyperpolarizing K + outward currents, thereby controlling smooth muscle contractility. Constitutive deletion of the BK channel in mice (BK −/− ) leads to an overactive bladder associated with increased intravesical pressure and frequent micturition, which has been revealed to be a result of detrusor muscle hyperexcitability. Interestingly, time‐dependent and smooth muscle‐specific deletion of the BK channel (SM‐BK −/− ) caused a more severe phenotype than displayed by constitutive BK −/− mice, suggesting that compensatory pathways are active in the latter. In detrusor muscle of BK −/− but not SM‐BK −/− mice, we found reduced L‐type Ca 2+ current density and increased expression of cAMP kinase (protein kinase A; PKA), as compared with control mice. Increased expression of PKA in BK −/− mice was accompanied by enhanced β‐adrenoceptor/cAMP‐mediated suppression of contractions by isoproterenol. This effect was attenuated by about 60–70% in SM‐BK −/− mice. However, the Rp isomer of adenosine‐3′,5′‐cyclic monophosphorothioate, a blocker of PKA, only partially inhibited enhanced cAMP signaling in BK −/− detrusor muscle, suggesting the existence of additional compensatory pathways. To this end, proteome analysis of BK −/− urinary bladder tissue was performed, and revealed additional compensatory regulated proteins. Thus, constitutive and inducible deletion of BK channel activity unmasks compensatory mechanisms that are relevant for urinary bladder relaxation.