bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verschränkte Spiegel. Ein realisierbares Gedankenexperiment
Authors: Schnabel Roman , Müller‐Ebhardt Helge , Rehbein Henning 
Published: August 2008

AbstractDie Herstellung von verschränkten Quantenobjekten aus Photonen oder Ionen ist bereits Routine. Da die Quantenmechanik der Größe und Schwere solcher Objekte keine prinzipielle Obergrenze setzt, sollten sich auch makroskopische Gegenstände miteinander verschränken lassen. Allerdings stellt das hohe Ansprüche an die Experimentiertechnik, vor allem im Bereich der Laser‐ und Kältetechnik, sowie an die Methoden zur Entkopplung der Objekte von der Umgebung. Die hier vorgestellte Idee nutzt einen Laserstrahl, um zwei massive Spiegel miteinander zu verschränken. Das entsprechende Experiment soll in den nächsten Jahren realisiert werden. Es könnte sogar eine Demonstration des Einstein‐Podolsky‐Rosen‐Paradoxons mit makroskopischen Objekten ermöglichen.
Kurzzeitaufnahmen von Molekülen
Authors: Meckel Moritz , Dörner Reinhard , Staudte André 
Published: August 2008

AbstractEine neue Technik ermöglicht es, in einem einzigen Experiment Informationen über das höchste besetzte Molekülorbital sowie den Bindungsabstand eines Moleküls zu gewinnen. Damit sind Physiker der J.W. Goethe‐Universität Frankfurt in Zusammenarbeit mit Kollegen am National Research Council of Canada dem Ziel näher gekommen, in Echtzeit zu beobachten, wie sich sowohl das atomare Gerüst als auch die Elektronenwolke eines Moleküls während einer chemischen Reaktion verändern.
A Comparative Study of Poly(propylene) Surface Oxidation in DC Low‐Pressure Oxygen and Water Vapor Discharges and in Flowing Afterglow of Water Vapor Discharge
Authors: Rybkin Vladimir , Kuvaldina Elena , Grinevich Andrey , Choukourov Andrey , Iwai Hideo , Biederman Hynek 
Published: September 2008

AbstractThe influence of direct current (DC) discharges in oxygen and water vapor and in a flowing afterglow of water vapor discharge onto the surface of poly(propylene) (PP) films was studied. The surface properties of PP were characterized by Fourier transform infrared by attenuated total reflectance (FTIR/ATR), X‐ray photoelectron spectroscopy (XPS), Atomic force microscopy (AFM), and contact angle measurement. The action of oxygen and water vapor plasma was found to be similar in terms of the composition of functional groups formed. Unlike plasma action, the PP surface treatment in water vapor discharge afterglow provided a more uniform composition of oxygen‐containing groups and greater depth of the modified layer. The formation of alcohol, carbonyl, and carboxyl groups has been observed. The treatment of PP films led to the increase in surface‐free energy, the polymer surface becoming more smooth and homogeneous.magnified image
Plasma Synthesis of Coated Metal Nanoparticles with Surface Properties Tailored for Dispersion
Authors: Tavares Jason , Swanson Edward J. , Coulombe Sylvain 
Published: September 2008

AbstractA method to produce copper nanoparticles coated with an organic plasma polymer layer is presented. The reaction mechanism for plasma polymerization of ethylene glycol is elucidated, and hydroxyl, methanol and ethanol radicals are shown to be present in the RF discharge. UV radiation is shown to have a significant effect on radical formation. Empirical evidence suggests that nanoparticles exhibit enhanced reactivity. Contact angle measurements of coated particles deposited onto copper collection surfaces show hydrophilic or hydrophobic properties when ethylene glycol or ethane, respectively, is used as the precursor gas. Such properties facilitate dispersion into other media by improving the interaction between the solid and liquid phases.magnified image
Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients
Authors: Naito Masayasu , Itoh Kyogo , Komatsu Nobukazu , Yamashita Yuichi , Shirakusa Takafumi , Yamada Akira , Moriya Fukuko , Ayatuka Hitoshi , Mohamed Elnisr Rashed , Matsuoka Kei , Noguchi Masanori 
Published: September 2008

AbstractBACKGROUNDTo evaluate the immunological responses of personalized peptide vaccination combined with low‐dose glucocorticoids for advanced hormone refractory prostate cancer (HRPC) patients (pts).METHODSEleven pts with advanced HRPC were treated with the vaccination and low‐dose glucocorticoids; 6 pts with 10 mg/day of prednisolone (PDL) followed by 1 mg/day of dexamethasone at the time of progression, 1 pt with PDL, and 4 pts with dexamethasone. Peptide‐specific cellular and humoral responses were employed to monitor pre‐ and post‐ (6th) vaccination samples.RESULTSThe vaccination combined with glucocorticoids was well tolerated with no severe adverse effects. Increments of IgG responses were observed in 1 of 4 or 8 of 10 pts tested who received PDL or dexamethasone, respectively, increment of cytotoxic T lymphocyte activity was observed in 2 of 4 or 5 of 7 pts tested, respectively. Vaccination with PDL or dexamethasone resulted in a decline of PSA (at least 50%) in 1 of 7 or 6 of 10 pts with significantly longer median TTP in the dexamethasone group, respectively.CONCLUSIONVaccination combined with dexamethasone could be recommended for further clinical trials from both immunological and clinical points of view. Prostate © 2008 Wiley‐Liss, Inc.
Long‐Term assessment of prostate cancer progression free survival: Evaluation of pathological parameters, nuclear shape and molecular biomarkers of pathogenesis
Authors: Veltri Robert W. , Isharwal Sumit , Miller M. Craig , Epstein Jonathan I. , Mangold Leslie A. , Humphreys Elizabeth , Partin Alan W. 
Published: September 2008

AbstractBackgroundMolecular pathways of proliferation, angiogenesis, neuroendocrine differentiation, apoptosis and alterations in nuclear structure of cancer epithelial cells are important in the pathogenesis of prostate cancer (PCa). Therefore, we evaluated the prognostic value of these parameters in 105 clinically localized PCa tumors with long‐term follow‐up after radical prostatectomy for progression‐free survival (PFS).MethodNuclear roundness variance (NRV) was calculated for tumor nuclei using the graphic tracing DynaCELL system. Immunohistochemistry assessed expression of Ki67, PCNA (proliferation), Chromogranin A (neuroendocrine differentiation), CD31 (angiogenesis), BCL2 (apoptosis), and Her‐2/neu (oncogene) in the tumors. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan–Meier plots were employed to analyze the data.ResultsGleason score, focal vs. non‐focal extra‐prostatic extension, organ confined status, NRV, Her‐2/neu, CD‐31 and Ki67 were univariately significant predictors of PFS. NRV was the most significant prognostic indicator with the highest concordance index (0.7) for PFS. Gleason score, NRV and Her‐2/neu were multivariately significant and yielded a concordance index of 0.77.ConclusionHer‐2/neu oncogene and NRV were shown to be significant in the prediction of PFS. The assessment of alterations in nuclear structure using NRV proved to be the most significant factor in the prediction of PFS. Integration of image analysis‐based NRV and molecular biomarkers with pathologic parameters should be considered for validation in the prediction of PFS. Prostate © 2008 Wiley‐Liss, Inc.
Structure‐based design of a T‐cell receptor leads to nearly 100‐fold improvement in binding affinity for pepMHC
Authors: Haidar Jaafar N. , Pierce Brian , Yu Yong , Tong Weiwei , Li Michael , Weng Zhiping 
Published: September 2008

AbstractT‐cell receptors (TCRs) are proteins that recognize peptides from foreign proteins bound to the major histocompatibility complex (MHC) on the surface of an antigen‐presenting cell. This interaction enables the T cells to initiate a cell‐mediated immune response to terminate cells displaying the foreign peptide on their MHC. Naturally occurring TCRs have high specificity but low affinity toward the peptide‐MHC (pepMHC) complex. This prevents the usage of solubilized TCRs for diagnosis and treatment of viral infections or cancers. Efforts to enhance the binding affinity of several TCRs have been reported in recent years, through randomized libraries and in vitro selection. However, there have been no reported efforts to enhance the affinity via structure‐based design, which allows more control and understanding of the mechanism of improvement. Here, we have applied structure‐based design to a human TCR to improve its pepMHC binding. Our design method evolved based on iterative steps of prediction, testing, and generating more predictions based on the new data. The final design function, named ZAFFI, has a correlation of 0.77 and average error of 0.35 kcal/mol with the binding free energies of 26 point mutations for this system that we measured by surface plasmon resonance (SPR). Applying the filter that we developed to remove nonbinding predictions, this correlation increases to 0.85, and the average error decreases to 0.3 kcal/mol. Using this algorithm, we predicted and tested several point mutations that improved binding, with one giving over sixfold binding improvement. Four of the point mutations that improved binding were then combined to give a mutant TCR that binds the pepMHC 99 times more strongly than the wild‐type TCR. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Zn2+‐linked dimerization of UreG from Helicobacter pylori, a chaperone involved in nickel trafficking and urease activation
Authors: Zambelli Barbara , Turano Paola , Musiani Francesco , Neyroz Paolo , Ciurli Stefano 
Published: September 2008

AbstractThe biosynthesis of the active metal‐bound form of the nickel‐dependent enzyme urease involves the formation of a lysine‐carbamate functional group concomitantly with the delivery of two Ni2+ ions into the precast active site of the apoenzyme and with GTP hydrolysis. In the urease system, this role is performed by UreG, an accessory protein belonging to the group of homologous P‐loop GTPases, often required to complete the biosynthesis of nickel‐enzymes. This study is focused on UreG from Helicobacter pylori (HpUreG), a bacterium responsible for gastric ulcers and cancer, infecting large part of the human population, and for which urease is a fundamental virulence factor. The soluble HpUreG was expressed in E. coli and purified to homogeneity. On‐line size exclusion chromatography and light scattering indicated that apo‐HpUreG exists as a monomer in solution. Circular dichroism, which demonstrated the presence of a well‐defined secondary structure, and NMR spectroscopy, which revealed a large number of residues that appear structured on the basis of their backbone amide proton chemical shift dispersion, indicated that, at variance with other UreG proteins so far characterized, this protein is significantly folded in solution. The amino acid sequence of HpUreG is 29% identical to that of HypB from Methanocaldococcus jannaschii, a dimeric zinc‐binding GTPase involved in the in vivo assembly of [Ni,Fe]‐hydrogenase. A homology‐based molecular model of HpUreG was calculated, which allowed us to identify structural and functional features of the protein. Isothermal titration microcalorimetry demonstrated that HpUreG specifically binds 0.5 equivalents of Zn2+ per monomer (Kd = 0.33 ± 0.03 μM), whereas it has 20‐fold lower affinity for Ni2+ (Kd = 10 ± 1 μM). Zinc ion binding (but not Ni2+ binding) causes protein dimerization, as confirmed using light scattering measurements. The structural rearrangement occurring upon Zn2+‐binding and consequent dimerization was evaluated using circular dichroism and fluorescence spectroscopy. Fully conserved histidine and cysteine residues were identified and their role in zinc binding was verified by site‐directed mutagenesis and microcalorimetry. The results are analyzed and discussed with respect to analogous examples of GTPases in nickel metabolism. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Crystal structure of Ultralente—A microcrystalline insulin suspension
Authors: Wagner Armin , Diez Joachim , Schulze‐Briese Clemens , Schluckebier Gerd 
Published: September 2008

AbstractUltralente insulin has been one of the commercially most important insulin preparations in diabetes treatment over the last 50 years. It is a suspension of insulin microcrystals which dissolve slowly following subcutaneous injection. Because of the small crystal size of about 25 × 25 × 5 μm3 the atomic structure has been elusive until now. Here we present the crystal structures from Ultralente and their precursor microcrystals from the industrial manufacturing process. During this process insulin undergoes a conformational change within the microcrystals. Both structures show canonical folding of the insulin molecules but exhibit a number of new features when compared with other insulin structures. Surprisingly, we found that the Ultralente crystals bind the conservation agent methylparaben, which slows down dissolution of the crystals and thus contributes to the long duration of action. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Solution structure of the Pseudomonas putida protein PpPutA45 and its DNA complex
Authors: Halouska Steven , Zhou Yuzhen , Becker Donald F. , Powers Robert 
Published: September 2008

AbstractProline utilization A (PutA) is a membrane‐associated multifunctional enzyme that catalyzes the oxidation of proline to glutamate in a two‐step process. In certain, gram‐negative bacteria such as Pseudomonas putida, PutA also acts as an auto repressor in the cytoplasm, when an insufficient concentration of proline is available. Here, the N‐terminal residues 1–45 of PutA from P. putida (PpPutA45) are shown to be responsible for DNA binding and dimerization. The solution structure of PpPutA45 was determined using NMR methods, where the protein is shown to be a symmetrical homodimer (12 kDa) consisting of two ribbon‐helix‐helix (RHH) structures. DNA sequence recognition by PpPutA45 was determined using DNA gel mobility shift assays and NMR chemical shift perturbations (CSPs). PpPutA45 was shown to bind a 14 base‐pair DNA oligomer (5′‐GCGGTTGCACCTTT‐3′). A model of the PpPutA45‐DNA oligomer complex was generated using Haddock 2.1. The antiparallel β‐sheet that results from PpPutA45 dimerization serves as the DNA recognition binding site by inserting into the DNA major groove. The dimeric core of four α‐helices provides a structural scaffold for the β‐sheet from which residues Thr5, Gly7, and Lys9 make sequence‐specific contacts with the DNA. The structural model implies flexibility of Lys9 which can make hydrogen bond contacts with either guanine or thymine. The high sequence and structure conservation of the PutA RHH domain suggest interdomain interactions play an important role in the evolution of the protein. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Identifying polymer‐forming SAM domains
Authors: Meruelo Alejandro D. , Bowie James U. 
Published: September 2008

AbstractSterile alpha motif (SAM) domains are common protein modules in eukaryotic cells. It has not been possible to assign functions to uncharacterized SAM domains because they have been found to participate in diverse functions ranging from protein–protein interactions to RNA binding. Here we computationally identify likely members of the subclass of SAM domains that form polymers. Sequences were virtually threaded onto known polymer structures and then evaluated for compatibility with the polymer. We find that known SAM polymers score better than the vast majority of known nonpolymers: 100% (7 of 7) of known polymers and only 8% of known nonpolymers (1 of 12) score above a defined threshold value. Of 2901 SAM family members, we find 694 that score above the threshold and are likely polymers, including SAM domains from the proteins Lethal Malignant Brain Tumor, Bicaudal‐C, Liprin‐β, Adenylate Cyclase, and Atherin. Proteins 2009. © 2008 Wiley‐Liss, Inc.
COCO: A simple tool to enrich the representation of conformational variability in NMR structures
Authors: Laughton Charles A. , Orozco Modesto , Vranken Wim 
Published: September 2008

AbstractNMR structures are typically deposited in databases such as the PDB in the form of an ensemble of structures. Generally, each of the models in such an ensemble satisfies the experimental data and is equally valid. No unique solution can be calculated because the experimental NMR data is insufficient, in part because it reflects the conformational variability and dynamical behavior of the molecule in solution. Even for relatively rigid molecules, the limited number of structures that are typically deposited cannot completely encompass the structural diversity allowed by the observed NMR data, but they can be chosen to try and maximize its representation. We describe here the adaptation and application of techniques more commonly used to examine large ensembles from molecular dynamics simulations, to the analysis of NMR ensembles. The approach, which is based on principal component analysis, we call COCO (“Complementary Coordinates”). The COCO approach analyses the distribution of an NMR ensemble in conformational space, and generates a new ensemble that fills “gaps” in the distribution. The method is very rapid, and analysis of a 25‐member ensemble and generation of a new 25 member ensemble typically takes 1–2 min on a conventional workstation. Applied to the 545 structures in the RECOORD database, we find that COCO generates new ensembles that are as structurally diverse—both from each other and from the original ensemble—as are the structures within the original ensemble. The COCO approach does not explicitly take into account the NMR restraint data, yet in tests on selected structures from the RECOORD database, the COCO ensembles are frequently good matches to this data, and certainly are structures that can be rapidly refined against the restraints to yield high‐quality, novel solutions. COCO should therefore be a useful aid in NMR structure refinement and in other situations where a richer representation of conformational variability is desired—for example in docking studies. COCO is freely accessible via the website www.ccpb.ac.uk/COCO. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Coevolution in defining the functional specificity
Authors: Chakrabarti Saikat , Panchenko Anna R. 
Published: September 2008

AbstractCovariation between sites can arise due to a common evolutionary history. At the same time, structure and function of proteins play significant role in evolvability of different sites that are not directly connected with the common ancestry. The nature of forces which cause residues to coevolve is still not thoroughly understood, it is especially not clear how coevolutionary processes are related to functional diversification within protein families. We analyzed both functional and structural factors that might cause covariation of specificity determinants and showed that they more often participate in coevolutionary relationships with each other and other sites compared with functional sites and those sites that are not under strong functional constraints. We also found that protein sites with higher number of coevolutionary connections with other sites have a tendency to evolve slower. Our results indicate that in some cases coevolutionary connections exist between specificity sites that are located far away in space but are under similar functional constraints. Such correlated changes and compensations can be realized through the stepwise coevolutionary processes which in turn can shed light on the mechanisms of functional diversification. Proteins 2009. Published 2008 Wiley‐Liss, Inc.
Solution structures and DNA binding properties of the N‐terminal SAP domains of SUMO E3 ligases from Saccharomyces cerevisiae and Oryza sativa
Authors: Suzuki Rintaro , Shindo Heisaburo , Tase Akira , Kikuchi Yoshiko , Shimizu Mitsuhiro , Yamazaki Toshimasa 
Published: September 2008

AbstractSUMO E3 ligase of the Siz/PIAS family that promotes sumoylation of target proteins contains SAP motif in its N‐terminal region. The SAP motif with a consensus sequence of 35 residues was first proposed to be as a new DNA binding motif found in diverse nuclear proteins involved in chromosomal organization. We have determined solution structures of the SAP domains of SUMO ligases Siz1 from yeast and rice by NMR spectroscopy, showing that the structure of the SAP domain (residues 2–105) of rice Siz1 is a four‐helix bundle with an up‐down‐extended loop‐down‐up topology, whereas the SAP domain (residues 1–111) of yeast Siz1 is comprised of five helices where the fifth helix α5 causes a significant change in the alignment of the four‐helix bundle characteristic to the SAP domains of the Siz/PIAS family. We have also demonstrated that both SAP domains have binding ability to an A/T‐rich DNA, but that binding affinity of yeast Siz1 SAP is at least by an order of magnitude higher than that of rice Siz1 SAP. Our NMR titration experiments clearly showed that yeast Siz1 SAP uses α2‐helix for DNA binding more effectively than rice Siz1 SAP, which would result from the dislocation of this helix due to the existence of the extra helix α5. In addition, based on the structures of the SAP domains determined here and registered in Protein Data Bank, general features of structures of the SAP domains are discussed in conjunction with equivocal nature of their DNA binding. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Satisfaction of hydrogen‐bonding potential influences the conservation of polar sidechains
Authors: Worth Catherine L. , Blundell Tom L. 
Published: September 2008

AbstractAlthough polar amino acids tend to be found on the surface of proteins due to their hydrophilic nature, their important roles within the core of proteins are now becoming better recognized. It has long been understood that a significant number of mainchain functions will not achieve hydrogen bond satisfaction through the formation of secondary structures; in these circumstances, it is generally buried polar residues that provide hydrogen bond satisfaction. Here, we describe an analysis of the hydrogen‐bonding of polar amino acids in a set of structurally aligned protein families. This allows us not only to calculate the conservation of each polar residue but also to assess whether conservation is correlated with the hydrogen‐bonding potential of polar sidechains. We show that those polar sidechains whose hydrogen‐bonding potential is satisfied tend to be more conserved than their unsatisfied or nonhydrogen‐bonded counterparts, particularly when buried. Interestingly, these buried and satisfied polar residues are significantly more conserved than buried hydrophobic residues. Forming hydrogen bonds to mainchain amide atoms also influences conservation, with those satisfied buried polar residues that form two hydrogen bonds to mainchain amides being significantly more conserved than those that form only one or none. These results indicate that buried polar residues whose hydrogen‐bonding potential is satisfied are likely to have important roles in maintaining protein structure. Proteins 2009. © 2008 Wiley‐Liss, Inc.