julilili42/papers huggingface dataset:
From interfaces to surfaces: soft x-ray spectromicroscopy investigations of diindenoperylene thin films on gold
2009-07-07

We present the results of photoemission electron microscopy investigations on diindenoperylene (DIP) thin films deposited on polycrystalline gold, prepared in order to have a roughness much larger than the molecular size. Our investigations revealed the ability of the DIP molecule to form well-organized films, exhibiting a different molecular orientation with respect to the already known λ and σ phases. In locally thicker film regions, the energy of the films is minimized by a molecular arrangement that has an asymptotic tendency to the σ phase.
A Convergence Study of QM/MM Isomerization Energies with the Selected Size of the QM Region for Peptidic Systems
2009-07-08

A systematic study of the convergence of QM/MM results with respect to the chosen size of the QM region is presented for two examples of peptidic systems. For this purpose, we increased the QM region to up to 1637 atoms at the HF/SVP and 383 atoms at the SOS-AO-MP2/6-31G** level. While the convergence behavior is almost independent of the chosen method and basis set, the study clearly shows that for the considered proton-transfer energy the QM/MM treatment leads to a significantly faster convergence than the pure QM treatment. This behavior can be rationalized by the fair description of the surrounding of the active center using MM methods, even though the MM description of the active center is not adequate in our present case. At the same time, the observed convergence is quite insensitive to a variation of charge surroundings in the chosen model peptides. Although the QM/MM results do converge much quicker with the system size than the pure QM ones, the data show that even for the chosen simple model systems about 150-300 QM atoms are needed to achieve accuracies in the order of 10 kJ/mol and about 300-1000 atoms for an accuracy of 2 kJ/mol with respect to a convergence with the QM-region size.
Thermal escape of fractional vortices in long Josephson junctions
2009-07-08

We consider a fractional Josephson vortex in a long 0-kappa Josephson junction. A uniformly applied bias current exerts a Lorentz force on the vortex. If the bias current exceeds the critical current, an integer fluxon is torn off the kappa-vortex and the junction switches to the voltage state. In the presence of thermal fluctuations the escape process takes place with finite probability already at subcritical values of the bias current. We experimentally investigate the thermally induced escape of a fractional vortex by high resolution measurements of the critical current as a function of the topological charge kappa of the vortex and compare the results to numerical simulations for finite junction lengths and to theoretical predictions for infinite junction lengths. To study the effect caused by the junction geometry we compare the vortex escape in annular and linear junctions.
Surface Organolanthanide and ‐Actinide Chemistry
2009-07-08

This chapter contains sections titled: Introduction Surface Organolanthanide Chemistry SOLnC Surface Organoactinide Chemistry, SOAnC Catalytic Applications of SOLnC and SOAnC Conclusions and Perspectives References
Comment on “DNA from Pre-Clovis Human Coprolites in Oregon, North America”
2009-07-09

Gilbert et al . (Reports, 9 May 2008, p. 786) presented DNA analysis of coprolites recovered from an Oregon cave as evidence for a human presence in North America before the Clovis culture. Results of our micromorphological and Fourier transform infrared spectroscopy analyses of one of the reported coprolites are difficult to reconcile with the DNA results identifying the coprolite as human.
Dissociable Perceptual Effects of Visual Adaptation
2009-07-09

Neurons in the visual cortex are responsive to the presentation of oriented and curved line segments, which are thought to act as primitives for the visual processing of shapes and objects. Prolonged adaptation to such stimuli gives rise to two related perceptual effects: a slow change in the appearance of the adapting stimulus (perceptual drift), and the distortion of subsequently presented test stimuli (adaptational aftereffects). Here we used a psychophysical nulling technique to dissociate and quantify these two classical observations in order to examine their underlying mechanisms and their relationship to one another. In agreement with previous work, we found that during adaptation horizontal and vertical straight lines serve as attractors for perceived orientation and curvature. However, the rate of perceptual drift for different stimuli was not predictive of the corresponding aftereffect magnitudes, indicating that the two perceptual effects are governed by distinct neural processes. Finally, the rate of perceptual drift for curved line segments did not depend on the spatial scale of the stimulus, suggesting that its mechanisms lie outside strictly retinotopic processing stages. These findings provide new evidence that the visual system relies on statistically salient intrinsic reference stimuli for the processing of visual patterns, and point to perceptual drift as an experimental window for studying the mechanisms of visual perception.
Processing of Two Latent Membrane Protein 1 MHC Class I Epitopes Requires Tripeptidyl Peptidase II Involvement
2009-07-09

Abstract The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential target for T cell immunotherapy in EBV-related malignancies. However, only a few CD8+ T cell epitopes are known, and the benefit of LMP1-specific T cell immunotherapy has not yet been proven. In this work, we studied the processing of the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL. We found that target cells endogenously expressing the native LMP1 are not recognized by CTLs specific for these epitopes because the N-terminal part of LMP1 limits the efficiency of epitope generation. We further observed that the proteasome is not required for the generation of both epitopes and that the YLLEMLRWL epitope seems to be destroyed by the proteasome, because blocking of proteasomal activities enhanced specific CTL activation. Activation of LMP1-specific CTLs could be significantly reduced after inhibition of the tripeptidyl peptidase II, suggesting a role for this peptidase in the processing of both epitopes. Taken together, our results demonstrate that the MHC class I-restricted LMP1 epitopes studied in this work are two of very few epitopes known to date to be processed proteasome independently by tripeptidyl peptidase II.
Meningitis as a Presentation of Macroprolactinoma
2009-07-09

Macroprolactinomas can present with meningitis without any prior history of CSF rhinorrhea. Surgical repair of the skull base defect is the treatment of choice in order to prevent further episodes of meningitis. Pituitary tumours should be considered as a cause of otherwise unexplained meningitis.
ChemInform Abstract: Formation of Pentacyclic Structures by a Domino Sequence on Cyclic Enamides.
2009-07-09

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
3,4-Diaryl-isoxazoles and -imidazoles as Potent Dual Inhibitors of p38α Mitogen Activated Protein Kinase and Casein Kinase 1δ
2009-07-10

In this study, we report on the discovery of isoxazole 1 as a potent dual inhibitor of p38alpha (IC(50) = 0.45 microM) and CK1delta (IC(50) = 0.23 microM). Because only a few effective small molecule inhibitors of CK1 have been described so far, we aimed to develop this structural class toward specific agents. Molecular modeling studies comparing p38alpha/CK1delta suggested an optimization strategy leading to design, synthesis, biological characterization, and SAR of highly potent compounds including 9 (IC(50) p38alpha = 0.006 microM; IC(50) CK1delta = 1.6 microM), 13 (IC(50) p38alpha = 2.52 microM; IC(50) CK1delta = 0.033 microM), 17 (IC(50) p38alpha = 0.019 microM; IC(50) CK1delta = 0.004 microM; IC(50) CK1epsilon = 0.073 microM), and 18 (CKP138) (IC(50) p38alpha = 0.041 microM; IC(50) CK1delta = 0.005 microM; IC(50) CK1epsilon = 0.447 microM) possessing differentiated specificity. Selected compounds were profiled over 76 kinases and evaluation of their cellular efficacy showed 18 (CKP138) to be a highly potent and dual-specific inhibitor of CK1delta and p38alpha.
Raman polarization studies of highly oriented organic thin films
2009-07-10

Abstract In this work we report on the capability of polarized Raman spectroscopy to investigate the structure of thin organic films. Diindenoperylene (DIP) thin films on (1 × 1)‐rutile(110) were prepared via organic molecular beam deposition (OMBD). Raman spectra of DIP thin films showed several strong Raman modes in the wavenumber region from 1200 to 1650 cm −1 . The A g mode at 1284 cm −1 shows two contributions, thereby indicating the coexistence of at least two DIP film structures. Polarized Raman spectroscopy was applied to characterize the molecular orientation and the dominance of the σ‐configuration (i.e. upright standing DIP molecules) was found. Copyright © 2009 John Wiley &amp; Sons, Ltd.
Spatial Control of 3D Energy Transfer in Supramolecular Nanostructured Host−Guest Architectures
2009-07-10

Systematic control of 3D energy transfer (ET) dynamics is achieved in supramolecular nanostructured host-guest systems using spacer-functionalized guest chromophores. Quantum chemistry-based Monte Carlo simulations reveal the strong impact of the spacer length on the ET dynamics, efficiency, and dimensionality. Remarkably high exciton diffusion lengths demonstrate that there is ample scope for optimizing oligomeric or polymeric optoelectronic devices.
Perturbation theory in the Hamiltonian approach to Yang-Mills theory in Coulomb gauge
2009-07-10

We study the Hamiltonian approach to Yang-Mills theory in Coulomb gauge in\\nRayleigh-Schroedinger perturbation theory. The static gluon and ghost\\npropagator as well as the potential between static colour sources are\\ncalculated to one-loop order. Furthermore, the one-loop -function is\\ncalculated from both the ghost-gluon vertex and the static potential and found\\nto agree with the result of covariant perturbation theory.\\n
Extracellular Iron Biomineralization by Photoautotrophic Iron-Oxidizing Bacteria
2009-07-11

ABSTRACT Iron oxidation at neutral pH by the phototrophic anaerobic iron-oxidizing bacterium Rhodobacter sp. strain SW2 leads to the formation of iron-rich minerals. These minerals consist mainly of nano-goethite (α-FeOOH), which precipitates exclusively outside cells, mostly on polymer fibers emerging from the cells. Scanning transmission X-ray microscopy analyses performed at the C K-edge suggest that these fibers are composed of a mixture of lipids and polysaccharides or of lipopolysaccharides. The iron and the organic carbon contents of these fibers are linearly correlated at the 25-nm scale, which in addition to their texture suggests that these fibers act as a template for mineral precipitation, followed by limited crystal growth. Moreover, we evidence a gradient of the iron oxidation state along the mineralized fibers at the submicrometer scale. Fe minerals on these fibers contain a higher proportion of Fe(III) at cell contact, and the proportion of Fe(II) increases at a distance from the cells. All together, these results demonstrate the primordial role of organic polymers in iron biomineralization and provide first evidence for the existence of a redox gradient around these nonencrusting, Fe-oxidizing bacteria.
Substantial early, but nonprogressive neuronal loss in multiple sclerosis (ms) spinal cord
2009-07-13

Abstract Research in multiple sclerosis (MS) has recently been focusing on the extent of neuroaxonal damage and its contribution to disease outcome. In the present study, we examined spinal cord tissue from 30 clinically well‐characterized MS patients. MS, amyotrophic lateral sclerosis (ALS), and control spinal cord tissue were subjected to morphometric analysis and immunohistochemistry for markers of cell damage and regeneration. Data were related to disease duration and age at death. Here, we present evidence for substantial, nonprogressive neuronal loss on the cervical and lumbar levels early in the disease course of MS. Chromatolytic neurons and immunoreactivity for c‐Jun and GAP43 were observed in the ventral gray matter in and adjacent to actively demyelinating lesions, pointing toward neuronal damage and regeneration as an early response to lesion formation. Ann Neurol 2009;66:698–704
Staphylococcus aureus Mutant Screen Reveals Interaction of the Human Antimicrobial Peptide Dermcidin with Membrane Phospholipids
2009-07-14

ABSTRACT Antimicrobial peptides (AMPs) form an important part of the innate host defense. In contrast to most AMPs, human dermcidin has an anionic net charge. To investigate whether bacteria have developed specific mechanisms of resistance to dermcidin, we screened for mutants of the leading human pathogen, Staphylococcus aureus , with altered resistance to dermcidin. To that end, we constructed a plasmid for use in mariner-based transposon mutagenesis and developed a high-throughput cell viability screening method based on luminescence. In a large screen, we did not find mutants with strongly increased susceptibility to dermcidin, indicating that S. aureus has no specific mechanism of resistance to this AMP. Furthermore, we detected a mutation in a gene of unknown function that resulted in significantly increased resistance to dermcidin. The mutant strain had an altered membrane phospholipid pattern and showed decreased binding of dermcidin to the bacterial surface, indicating that dermcidin interacts with membrane phospholipids. The mode of this interaction was direct, as shown by assays of dermcidin binding to phospholipid preparations, and specific, as the resistance to other AMPs was not affected. Our findings indicate that dermcidin has an exceptional value for the human innate host defense and lend support to the idea that it evolved to evade bacterial resistance mechanisms targeted at the cationic character of most AMPs. Moreover, they suggest that the antimicrobial activity of dermcidin is dependent on the interaction with the bacterial membrane and might thus assist with the determination of the yet unknown mode of action of this important human AMP.
Arylpyrrolizines as Inhibitors of Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) or as Dual Inhibitors of mPGES-1 and 5-Lipoxygenase (5-LOX)
2009-07-14

We synthesized and evaluated inhibitors for the microsomal prostaglandin E2 synthase-1 (mPGES-1), based on the arylpyrrolizine scaffold. In a cell free mPGES-1 assay several "sulfonimides" exceeded our lead ML3000 (3) in potency. The most promising compound, the tolylsulfonimide 11f, revealed an IC50 of 2.1 microM and is equipotent to the literature reference molecule MK886 (1). Selected compounds also potently reduced 5-LOX product formation in intact cells. Inhibition of isolated COX was occasionally remarkably cut down.
Evidence for inhibition of leptin secretion by catecholamines in man
2009-07-14

The regulation of leptin secretion is complex and not entirely understood in humans. Insulin has been shown to stimulate leptin secretion in humans, whereas in vitro data suggest that catecholamines inhibit leptin secretion. The present studies were therefore undertaken to examine the leptin response to hyperinsulinemia in the presence and absence of elevated plasma levels of endogenous catecholamines in humans. Leptin concentrations were determined during both a euglycemic and hypoglycemic hyperinsulinemic clamp study in 10 normal and 10 type I diabetic subjects. Serum leptin increased during the hyperinsulinemic euglycemic clamp in normal (from 6.1 +/- 0.9 to 7.2 +/- 1.1 ng/dl, p = 0.003) and diabetic subjects (from 6.2 +/- 1.4 to 7.8 +/- 1.8 ng/dl, p = 0.001). During hyperinsulinemic hypoglycemia leptin concentrations increased significantly in type 1 diabetic patients (from 5.6 +/- 1.1 to 7.6 +/- 1.7 ng/dl, p = 0.003) but remained unaltered in normals (from 5.5 +/- 0.7 to 5.7 +/- 0.9 ng/dl, p = 0.7). During hypoglycemia in all subjects the increase in leptin was negatively correlated with the increase in epinephrine (r = 0.60, p = 0.005) and positively with the decrease in free fatty acids (r = 0.71, p = 0.003). In conclusion our results indicate that catecholamines play a suppressive role in the regulation of leptin secretion.
Differential afferent sensitivity to mucosal lipopolysaccharide from Salmonella typhimurium and Escherichia coli in the rat jejunum
2009-07-14

Abstract Postinfectious irritable bowel syndrome may develop subsequent to acute bacterial enteritis. We therefore hypothesized that intestinal afferents may develop hypersensitivity upon exposure to luminal lipopolysaccharide (LPS) from pathogens but not from commensal bacteria and that this may be prostaglandin mediated. Extracellular recordings of jejunal afferents were obtained in vivo from male Wistar rats ( n = 5 per group; 300–400 g). Lipopolysaccharide from Escherichia coli (E‐LPS), Salmonella typhimurium (S‐LPS) or vehicle were infused into the intestinal lumen at 5 mg mL −1 . The selective 5‐HT 3 ‐receptor agonist 2‐methyl‐5‐HT (2m5‐HT, 15 μ gkg −1 , i.v.) was administered at 15‐min intervals before and up to 2 h after S‐LPS administration. Intraluminal E‐LPS had no effect on mesenteric afferent nerve discharge at baseline. By contrast, afferent discharge increased from 21.7 ± 0.3 impsec −1 to 28.8 ± 3.4 impsec −1 40 min after S‐LPS administration (mean ± SEM; P &lt; 0.05) and reached 38.8 ± 4.1 impsec −1 after 2 h ( P &lt; 0.05). The afferent response to 2m5‐HT was enhanced 30 min following S‐LPS by 30.9 ± 3.9% ( P &lt; 0.05) and remained elevated thereafter. The increase in baseline discharge and sensitivity to 2m5‐HT following S‐LPS was prevented by pretreatment with naproxen (COX inhibitor, 10 mgkg −1 i.v.) or AH‐6809 (EP1/EP2 receptor antagonist, 1 mg kg −1 ). Intestinal afferents do not alter their discharge rate to LPS from E. coli but to LPS from the pathogenic bacterium S. typhimurium . The latter response entails afferent sensitisation to 2m5‐HT that depends on prostanoid release. This acute sensitisation may prime the intestinal afferent innervation for a later development of persistent hypersensitivity.
Insulin Action and Secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight
2009-07-14

It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance.
Hyper- and hypoinsulinemia in type-2 diabetes: What may be wrong in the secretory mechanism of the B-cell
2009-07-14

Type-2 diabetes frequently is the consequence of overnutrition causing overweight, which then produces insulin resistance. The following hyperglycemia induces permanent overstimulation of the insulin secretory machinery of the B-cell, which results in hyperinsulinemia and/or hypoinsulinemia. The mechanisms, however, of these disturbances are not understood so far. Animal models, which can be used to solve these questions, are, among others, long-term incubation of pancreatic islets in culture in the presence of high glucose and/or long-term infusion of rats with glucose. Using these models sensitization [Bedoya and Jeanrenaud, 1991; Leahy et al., 1987; Purrello et al., 1992; Thams, 1991; Thibault et al., 1993; Timmers et al., 1990] and/or desensitization of insulin release [Bedoya and Jeanrenaud, 1991; Leahy et al., 1987; Davalli et al., 1992; Eizirik et al., 1992; Bolaffi et al., 1988; Timmers et al., 1990] have been reported. Whether or not there is sensitization or desensitization depends on the glucose concentration [Eizirik et al., 1992; Leahy et al., 1986; Sako and Grill, 1990] and the duration of glucose action [Bedoya and Jeanrenaud, 1991; Bolaffi et al., 1988]. Both, sensitization and desensitization, appear to be reversible on return to normal glucose or mild hypoglycemia [Leahy and Weir, 1991; Svenson and Hellerström, 1991]. It seems, however, that there is a fluent change from the first occurring hyperinsulinemia to hypoinsulinemia. In this lecture I first want to talk about the possible mechanism of sensitization of insulin secretion discussing previous results we have obtained from rat islets isolated after a 48 hours period of i.v. infusion with 50% glucose. In the second part I will discuss some of the findings coming from the respective literature concerning desensitization of insulin secretion.