julilili42/papers huggingface dataset:
Synthesis and Biological Testing of N‐Aminoimidazole‐Based p38α MAP Kinase Inhibitors
2010-05-14

Abstract The p38 mitogen‐activated protein (MAP) kinase α plays a central role in the regulation of cellular responses such as differentiation, proliferation, apoptosis, and inflammation. Inhibition of p38 results in decreased synthesis of pro‐inflammatory cytokines. To date, diverse p38α inhibitors are in phase II clinical trials for numerous cytokine‐dependent diseases. 2‐Sulfanylimidazole derivatives offer advantages over the prototype inhibitor SB 203580, including fewer cytochrome P450 interactions and better kinetic properties. The aim of this study was to develop novel 1,2,4,5‐tetrasubstituted pyridinylimidazoles with acyl residues at the imidazole N1 position that can interact with the kinase's hydrophobic region II (HR II) or sugar pocket (SP) to improve both selectivity and activity. The substitution pattern was optimized by variation of the acyl moiety at the N1 position of the N ‐aminoimidazole core. Acylation of the amino function was used for optimization and led to potent p38α MAPK inhibitors.
Palladium Chemistry with Stanna‐closo‐dodecaborate and Isocyanides
2010-05-14

Abstract The substitution equilibrium between isocyanides and stanna‐ closo ‐dodecaborate with palladium(II) was investigated. The mixed substituted products of type [(RNC) 2 Pd(SnB 11 H 11 ) 2 ] 2– and [(RNC)Pd(SnB 11 H 11 ) 3 ] 4– were characterized by X‐ray crystal structure analysis, elemental analysis and NMR spectroscopy. Isocyanide insertion into palladium–carbon bonds was also found. The zwitterionic complexes isolated from the reaction of [(P′ 2 )Pd(Me)(SnB 11 H 11 )] – (P′ 2 = dppe, dppp, dppf) with isocyanides were characterized.
Life-threatening pneumonia caused by human cytomegalovirus and Mycoplasma pneumoniae coinfection in a young, immunocompetent patient
2010-05-14

A young, previously healthy and immunocompetent patient was transferred to our hospital to recover a suspected Ascaris worm from his gall bladder. Although the diagnosis of Ascaris infection could not be confirmed, the patient suffered from cholecystitis. To our surprise, the respiratory situation of the patient deteriorated within 24 h under antibiotic therapy and he had to be transferred to the intensive care unit for mechanical respiration. Human cytomegalovirus (HCMV) was isolated directly from a bronchoalveolar lavage (BAL) sample, and Mycoplasma pneumoniae DNA was detected by PCR in an enrichment culture of the same BAL sample. Serology for HCMV and M. pneumoniae clearly supported a primary/post-primary infection for both agents (IgM detection, increase of IgG titres and, in the case of HCMV, a low avidity index of only 22 %). Therefore, we assumed that a rare HCMV and M. pneumoniae coinfection was the aetiology of the fulminant pneumonia. Under broad antibiotic and antiviral treatment, the situation of the patient improved only very slowly.
Maxillofacial Osseous Reconstruction Using the Angular Branch of the Thoracodorsal Vessels
2010-05-14

Mandibular and maxillary resections can produce complex three-dimensional defects requiring skeletal, soft tissue, and epithelial reconstruction. The subscapular vascular axis offers a source of skin, bone, and muscle on a single pedicle for microvascular flap transfer. We reviewed four cases where the subscapular vascular pedicle was used as a source of tissue for complex facial reconstructions in maxillofacial defects. Reconstruction of these complex defects was performed with a latissimus dorsi muscle or myocutaneous flap in combination with the lateral border of the scapula, harvested on the angular branch of the thoracodorsal vessels. There were three cases of maxillectomy and one case of partial mandibulectomy for malignant tumors. In each case, the angular branch of the thoracodorsal artery supplied 6 to 8 cm of the lateral border of the scapula and a latissimus dorsi myocutaneous flap was used for soft tissue reconstruction. Follow-up ranged from 9 months to 3 years and in all cases there was successful bony union. Shoulder movement was normal. This series encourages the further use of subscapular axis flaps as flexible sources of combined myocutaneous and osseous flaps on a single vascular pedicle in cases of complex maxillofacial reconstruction.
New insights into the complex structure and ontogeny of the occipito‐vertebral gap in barbeled dragonfishes (Stomiidae, Teleostei)
2010-05-17

Abstract In all stomiid genera there is an occipito‐vertebral gap between the skull and the first vertebra bridged only by the flexible notochord. Morphological studies from the early 20th century suggested that some stomiid genera have 1–10 of the anteriormost centra reduced or entire vertebrae missing in this region. Our study reviews this previous hypothesis. Using a new approach, we show that only in Chauliodus , Eustomias and Leptostomias gladiator vertebral centra are actually lost, with their respective neural arches and parapophyses persisting. We present results from a comparative analysis of the number and insertion sites of the anteriormost myosepta in 26 of the 28 stomiid genera. Generally in teleosts the first three myosepta are associated with the occiput, and the fourth is the first vertebral myoseptum. The insertion site of the fourth myoseptum plays an important role in this analysis, because it provides a landmark for the first vertebra. Lack of association of the fourth myoseptum with a vertebra is thus evidence that the first vertebra is reduced or absent. By counting the occipital and vertebral myosepta the number of reduced vertebrae in Chauliodus , Eustomias and Leptostomias gladiator can be inferred. Proper identification of the spino‐occipital nerves provides an additional source of information about vertebral reduction. In all other stomiid genera the extensive occipito‐ vertebral gap is not a consequence of the reduction of vertebrae, but of an elongation of the notochord. The complex structure and ontogeny of the anterior part of the vertebral column of stomiids are discussed comparatively. J. Morphol. 271:1006–1022, 2010. © 2010 Wiley‐Liss, Inc.
Charged anti–de Sitter scalar-tensor black holes and their thermodynamic phase structure
2010-05-17

In the present paper we numerically construct new charged anti-de Sitter\\nblack holes coupled to nonlinear Born-Infeld electrodynamics within a certain\\nclass of scalar-tensor theories. The properties of the solutions are\\ninvestigated both numerically and analytically. We also study the\\nthermodynamics of the black holes in the canonical ensemble. For large values\\nof the Born-Infeld parameter and for a certain interval of the charge values we\\nfind the existence of a first-order phase transition between small and very\\nlarge black holes. An unexpected result is that for a certain small charge\\nsubinterval two phase transitions have been observed, one of zeroth and one of\\nfirst order. It is important to note that such phase transitions are also\\nobserved for pure Einstein-Born-Infeld-AdS black holes.\\n
Probabilistic Modeling of Conformational Space for 3D Machine Learning Approaches
2010-05-17

Abstract We present a new probabilistic encoding of the conformational space of a molecule that allows for the integration into common similarity calculations. The method uses distance profiles of flexible atom‐pairs and computes generative models that describe the distance distribution in the conformational space. The generative models permit the use of probabilistic kernel functions and, therefore, our approach can be used to extend existing 3D molecular kernel functions, as applied in support vector machines, to build QSAR models. The resulting kernels are valid 4D kernel functions and reduce the dependency of the model quality on suitable conformations of the molecules. We showed in several experiments the robust performance of the 4D kernel function, which was extended by our approach, in comparison to the original 3D‐based kernel function. The new method compares the conformational space of two molecules within one kernel evaluation. Hence, the number of kernel evaluations is significantly reduced in comparison to common kernel‐based conformational space averaging techniques. Additionally, the performance gain of the extended model correlates with the flexibility of the data set and enables an a priori estimation of the model improvement.
G-Box Binding Factor1 Reduces CATALASE2 Expression and Regulates the Onset of Leaf Senescence in Arabidopsis
2010-05-18

Abstract Hydrogen peroxide (H2O2) is discussed as being a signaling molecule in Arabidopsis (Arabidopsis thaliana) leaf senescence. Intracellular H2O2 levels are controlled by the H2O2-scavenging enzyme catalase in concert with other scavenging and producing systems. Catalases are encoded by a small gene family, and the expression of all three Arabidopsis catalase genes is regulated in a senescence-associated manner. CATALASE2 (CAT2) expression is down-regulated during bolting time at the onset of leaf senescence and appears to be involved in the elevation of the H2O2 level at this time point. To understand the role of CAT2 in senescence regulation in more detail, we used CAT2 promoter fragments in a yeast one-hybrid screen to isolate upstream regulatory factors. Among others, we could identify G-Box Binding Factor1 (GBF1) as a DNA-binding protein of the CAT2 promoter. Transient overexpression of GBF1 together with a CAT2:β-glucuronidase construct in tobacco (Nicotiana benthamiana) plants and Arabidopsis protoplasts revealed a negative effect of GBF1 on CAT2 expression. In gbf1 mutant plants, the CAT2 decrease in expression and activity at bolting time and the increase in H2O2 could no longer be observed. Consequently, the onset of leaf senescence and the expression of senescence-associated genes were delayed in gbf1 plants, clearly indicating a regulatory function of GBF1 in leaf senescence, most likely via regulation of the intracellular H2O2 content.
CD99 and CD99L2 act at the same site as, but independently of, PECAM-1 during leukocyte diapedesis
2010-05-18

Abstract Leukocyte extravasation depends on various adhesion receptors at endothelial cell contacts. Here we have analyzed how mouse CD99 and CD99L2 cooperate with PECAM-1. We found that antibodies against mouse CD99 and PECAM-1 trap neutrophils between endothelial cells in in vitro transmigration assays. A sequential function, as has been suggested for human PECAM-1 and CD99, could not be demonstrated. In contrast to these in vitro results, blocking CD99 or CD99L2 or gene disruption of PECAM-1 trapped neutrophils in vivo between endothelial cells and the underlying basement membrane as revealed by electron microscopy and by 3-dimensional confocal fluorescence microscopy in the inflamed cremaster tissue. Leukocyte extravasation was inhibited in interleukin-1β-inflamed peritoneum and in the cremaster by PECAM-1 gene disruption and was further attenuated by blocking antibodies against CD99 and CD99L2. In addition, CD99 and CD99L2 were required for leukocyte extravasation in the cremaster after stimulation with tumor necrosis factor-α, where the need for PECAM-1 is known to be bypassed. We conclude that CD99 and CD99L2 act independently of PECAM-1 in leukocyte extravasation and cooperate in an independent way to help neutrophils overcome the endothelial basement membrane.
Quantitative Assessment of Intrahepatic Lipids Using Fat-Selective Imaging With Spectral-Spatial Excitation and In-/Opposed-Phase Gradient Echo Imaging Techniques Within a Study Population of Extremely Obese Patients
2010-05-18

The presented data confirm that both methods are reliable tools for quantification of IHL, if inherent drawbacks and limitations are taken into account. Inhomogeneity of the static magnetic field observed in examinations of extremely obese patients limits the use of spectral-spatial excitation, if performed without time-consuming shimming procedures. Necessity to correct for transverse and longitudinal relaxation effects using the IN/OP method requires additional measurements and postprocessing procedures, which might hamper the clinical applicability. Moreover, significant regional differences in IHL may exist in some patients especially if pronounced hepatic steatosis is present.
Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration
2010-05-19

Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl 4 , a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.
Starvation-induced Hyperacetylation of Tubulin Is Required for the Stimulation of Autophagy by Nutrient Deprivation
2010-05-19

The molecular mechanisms underlying microtubule participation in autophagy are not known. In this study, we show that starvation-induced autophagosome formation requires the most dynamic microtubule subset. Upon nutrient deprivation, labile microtubules specifically recruit markers of autophagosome formation like class III-phosphatidylinositol kinase, WIPI-1, the Atg12-Atg5 conjugate, and LC3-I, whereas mature autophagosomes may bind to stable microtubules. We further found that upon nutrient deprivation, tubulin acetylation increases both in labile and stable microtubules and is required to allow autophagy stimulation. Tubulin hyperacetylation on lysine 40 enhances kinesin-1 and JIP-1 recruitment on microtubules and allows JNK phosphorylation and activation. JNK, in turn, triggers the release of Beclin 1 from Bcl-2-Beclin 1 complexes and its recruitment on microtubules where it may initiate autophagosome formation. Finally, although kinesin-1 functions to carry autophagosomes in basal conditions, it is not involved in motoring autophagosomes after nutrient deprivation. Our results show that the dynamics of microtubules and tubulin post-translational modifications play a major role in the regulation of starvation-induced autophagy.
Helicity parton distributions from spin asymmetries inW-boson production at RHIC
2010-05-19

We present a next-to-leading order QCD calculation of the cross section and\\nlongitudinal spin asymmetry in single-inclusive charged-lepton production, pp\\n-&gt; l X, at RHIC, where the lepton is produced in the decay of an electroweak\\ngauge boson. Our calculation is presented in terms of a multi-purpose\\nMonte-Carlo integration program that may be readily used to include\\nexperimental spin asymmetry data in a global analysis of helicity parton\\ndensities. We perform a toy global analysis, studying the impact of anticipated\\nRHIC data on our knowledge about the polarized anti-quark distributions.\\n
PET/CT with 18F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?
2010-05-19

PET-negative residual masses after chemotherapy of metastatic GCT still require resection, since the low negative predictive value of (18)F-FDG PET for viable tumor cannot be improved by application of (18)F-FLT.
Silver Dimer, Tetramer, Polymer, and Network Structures with the Stannylene Stanna-closo-dodecaborate
2010-05-19

The reaction of the tin nucleophile stanna-closo-dodecaborate [SnB11H11]2− with silver electrophiles resulted in the formation of silver−tin complexes. Depending on the respective co-ligands, a dimer, a tetramer, a polymer, and a three-dimensional network structure were characterized. With bipyridine and phenanthroline, dimeric complexes exhibiting very short Ag−Ag interatomic distances were isolated. With t-BuNC and pyridine, tetranuclear clusters showing tetrahedral geometry were crystallized. From the reaction of the silver salt [Et4N]8[Ag4(SnB11H11)6] with the bridging ligand 1,4-diisocyanobenzene (DIB) a linear polymeric coordination compound was formed, and a three-dimensional network structure was the product from the reaction of 1,4-diisocyanobenzene with the silver salt [Me4N][Ag(SnB11H11)]. The coordination compounds were characterized by X-ray crystal structure analysis and elemental analysis. In the case of the three-dimensional network material {[Me4N]4[Ag4(SnB11H11)4(DIB)6/2]}n (12) a single crystal to single crystal solvent exchange was found.
The Arabidopsis Mitogen-Activated Protein Kinase Phosphatase PP2C5 Affects Seed Germination, Stomatal Aperture, and Abscisic Acid-Inducible Gene Expression
2010-05-20

Abstract Abscisic acid (ABA) is an important phytohormone regulating various cellular processes in plants, including stomatal opening and seed germination. Although protein phosphorylation via mitogen-activated protein kinases (MAPKs) has been suggested to be important in ABA signaling, the corresponding phosphatases are largely unknown. Here, we show that a member of the Protein Phosphatase 2C (PP2C) family in Arabidopsis (Arabidopsis thaliana), PP2C5, is acting as a MAPK phosphatase. The PP2C5 protein colocalizes and directly interacts with stress-induced MPK3, MPK4, and MPK6, predominantly in the nucleus. Importantly, altered PP2C5 levels affect MAPK activation. Whereas Arabidopsis plants depleted of PP2C5 show an enhanced ABA-induced activation of MPK3 and MPK6, ectopic expression of PP2C5 in tobacco (Nicotiana benthamiana) resulted in the opposite effect, with the two MAPKs salicylic acid-induced protein kinase and wound-induced protein kinase not being activated any longer after ABA treatment. Moreover, depletion of PP2C5, whose gene expression itself is affected by ABA treatment, resulted in altered ABA responses. Loss-of-function mutation in PP2C5 or AP2C1, a close PP2C5 homolog, resulted in an increased stomatal aperture under normal growth conditions and a partial ABA-insensitive phenotype in seed germination that was most prominent in the pp2c5 ap2c1 double mutant line. In addition, the response of ABA-inducible genes such as ABI1, ABI2, RD29A, and Erd10 was reduced in the mutant plants. Thus, we suggest that PP2C5 acts as a MAPK phosphatase that positively regulates seed germination, stomatal closure, and ABA-inducible gene expression.
Sugammadex: a selective relaxant-binding agent providing rapid reversal
2010-05-20

Sugammadex binds amino-steroidal muscle relaxants by encapsulation. It enables rapid reversal of neuromuscular blockade at any time point and at any depth of block. Its effects are predictable and very reliable, in contrast to cholinesterase inhibitors. This opens up new perspectives in anaesthesia. Even an emergency reversal of high-dose rocuronium-induced neuromuscular blockade is possible with sugammadex and times to full recovery (TOF 0.9) are faster than after spontaneous recovery from suxamethonium.
Automatic Lumen Segmentation in Calcified Plaques: Dual-Energy CT Versus Standard Reconstructions in Comparison With Digital Subtraction Angiography
2010-05-20

Dual-energy CT with plaque removal automatically delivers CT luminograms with a high sensitivity for the detection of relevant stenoses and a higher correlation to DSA than standard reconstructions but frequently leads to an overestimation of high-grade stenoses as occlusions. Thus, dual-energy CT plaque and bone removal should be used complementary to standard reconstructions, and not exclusively.
Unexpected Reaction of 2-Alkylsulfanylimidazoles to Imidazol-2-ones: Pyridinylimidazol-2-ones as Novel Potent p38α Mitogen-Activated Protein Kinase Inhibitors
2010-05-20

While optimizing the synthesis of 2-alkylsulfanyl-5-(2-aminopyridin-4-yl)imidazoles, we identified an unexpected reaction to pyridinylimidazol-2-ones. 2-Alkylsulfanylimidazoles, bearing a 2-hydroxyethyl or a 2,3-dihydroxypropyl moiety at the imidazole C2-S position, were converted by heating into imidazol-2-ones. These imidazol-2-ones were tested for their ability to inhibit p38alpha MAP kinase and LPS-stimulated TNF-alpha release in HWB. Introduction of an amino moiety at the pyridine C2 position led to compounds showing potent enzyme inhibitory activity with double-digit nanomolar IC(50) values (5a: IC(50) = 23 nM).
Presumed Tuberculosis-induced Retinal Vasculitis, Diagnosed with Positron Emission Tomography (18F-FDG-PET/CT), Aspiration Biopsy, and Culture
2010-05-20

The authors favor the use of (18)F-FDG-PET/CT in patients with sight-threatening intraocular inflammation and positive interferon-gamma release assay. Anti-tubercular therapy, together with anti-inflammatory treatment, may lead to a remission in such patients.
Results of the GREAT08 Challenge★: an image analysis competition for cosmological lensing
2010-05-21

We present the results of the Gravitational LEnsing Accuracy Testing 2008 (GREAT08) Challenge, a blind analysis challenge to infer weak gravitational lensing shear distortions from images. The primary goal was to stimulate new ideas by presenting the problem to researchers outside the shear measurement community. Six GREAT08 Team methods were presented at the launch of the Challenge and five additional groups submitted results during the 6-month competition. Participants analyzed 30 million simulated galaxies with a range in signal-to-noise ratio, point spread function ellipticity, galaxy size and galaxy type. The large quantity of simulations allowed shear measurement methods to be assessed at a level of accuracy suitable for currently planned future cosmic shear observations for the first time. Different methods perform well in different parts of simulation parameter space and come close to the target level of accuracy in several of these. A number of fresh ideas have emerged as a result of the Challenge including a re-examination of the process of combining information from different galaxies, which reduces the dependence on realistic galaxy modelling. The image simulations will become increasingly sophisticated in future GREAT Challenges, meanwhile the GREAT08 simulations remain as a benchmark for additional developments in shear measurement algorithms.
Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts
2010-05-21

The exo-peptidase cathepsin X has been identified as a new member of the group of CXCL-12-degrading enzymes secreted by non-hematopoietic bone marrow cells. Functional data indicate that cathepsin X can influence hematopoietic stem and progenitor cell trafficking in the bone marrow.