bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structures of the Arabidopsis thaliana proliferating cell nuclear antigen 1 and 2 proteins complexed with the human p21 C‐terminal segment
Authors: Strzalka Wojciech , Oyama Takuji , Tori Kazuo , Morikawa Kosuke 
Published: March 2009

AbstractThe proliferating cell nuclear antigen (PCNA) is well recognized as one of the essential cellular components of the DNA replication machinery in all eukaryotic organisms. Despite their prominent importance, very little biochemical and structural information about plant PCNAs is available, in comparison with that obtained from other eukaryotic organisms. We have determined the atomic resolution crystal structures of the two distinct Arabidopsis thaliana PCNAs (AtPCNA), both complexed with the C‐terminal segment of human p21. Both AtPCNAs form homotrimeric ring structures, which are essentially identical to each other, including the major contacts with the p21 peptide. The structure of the amino‐terminal half of the p21 peptide, containing the typical PIP box sequence, is remarkably similar to those observed in the previously reported crystal structures of the human and archaeal PCNA‐PIP box complexes. Meanwhile, the carboxy‐terminal halves of the p21 peptide in the plant PCNA complexes are bound to the protein in a unique manner, most probably because of crystal packing effects. A surface plasmon resonance analysis revealed high affinity between each AtPCNA and the C‐terminal fragment of human p21. This result strongly suggests that the interaction is functionally significant, although no plant homologs of p21 have been identified yet. We also discovered that AtPCNA1 and AtPCNA2 form heterotrimers, implying that hetero‐PCNA rings may play critical roles in cellular signal transduction, particularly in DNA repair.
Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas
Authors: Clementi Marisa , Sánchez Catherine , Benitez Dixan A. , Contreras Héctor R. , Huidobro Christian , Cabezas Juan , Acevedo Cristian , Castellón Enrique A. 
Published: March 2009

AbstractBACKGROUNDGonadotropin‐releasing‐hormone (GnRH) analogs are widely used to block hypothalamic–pituitary–gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH‐mediated apoptosis on prostate cancer cells were studied.METHODSPrimary cultures from PCa and benign prostatic hyperplasia (BPH) (non‐malignant control) were derived from samples provided by our Institutional Hospital. Cell cultures were incubated for 24 hr with 20 ng/ml of GnRH agonist Leuprolide (Lp) or antagonist Cetrorelix (Cx). Apoptosis was evaluated by studying the expression of Bax and Bcl‐2 and the activation of caspase‐9 (intrinsic pathway), caspase‐8 (extrinsic pathway), and caspase‐3. Also, mRNA level, protein expression and phosphorylation of p53 were studied.RESULTSCleaved caspase‐8 and ‐3, but not ‐9, increased in presence of Lp and Cx in PCa cell cultures. Bax and Bcl‐2 mRNA levels showed no changes after GnRH‐analog treatments. Only Bax protein showed an increase after Cx treatment in PCa cell cultures. p53 mRNA level was higher in PCa than in BPH cell cultures. Lp and Cx increased p53 expression and phosphorylation in PCa cell cultures.CONCLUSIONSApoptosis induced by GnRH analogs seems to be mediated by extrinsic pathway involving p53 phosphorylation. Phosphorylated‐p53 might be associated with the increase in apoptotic NGF receptor, p75, previously reported by our laboratory. These findings reinforce the concept of clinical use of GnRH analogs for PCa suggesting that intraprostatic treatment may be more effective. Prostate 69:1025–1033, 2009. © 2009 Wiley‐Liss, Inc.
Time‐dependent insulin oligomer reaction pathway prior to fibril formation: Cooling and seeding
Authors: Sorci Mirco , Grassucci Robert A. , Hahn Ingrid , Frank Joachim , Belfort Georges 
Published: March 2009

AbstractThe difficulty in identifying the toxic agents in all amyloid‐related diseases is likely due to the complicated kinetics and thermodynamics of the nucleation process and subsequent fibril formation. The slow progression of these diseases suggests that the formation, incorporation, and/or action of toxic agents are possibly rate limiting. Candidate toxic agents include precursors (some at very low concentrations), also called oligomers and protofibrils, and the fibrils. Here, we investigate the kinetic and thermodynamic behavior of human insulin oligomers (imaged by cryo‐EM) under fibril‐forming conditions (pH 1.6 and 65°C) by probing the reaction pathway to insulin fibril formation using two different types of experiments—cooling and seeding—and confirm the validity of the nucleation model and its effect on fibril growth. The results from both the cooling and seeding studies confirm the existence of a time‐changing oligomer reaction process prior to fibril formation that likely involves a rate‐limiting nucleation process followed by structural rearrangements of intermediates (into β‐sheet rich entities) to form oligomers that then form fibrils. The latter structural rearrangement step occurs even in the absence of nuclei (i.e., with added heterologous seeds). Nuclei are formed at the fibrillation conditions (pH 1.6 and 65°C) but are also continuously formed during cooling at pH 1.6 and 25°C. Within the time‐scale of the experiments, only after increasing the temperature to 65°C are the trapped insulin nuclei and resultant structures able to induce the structural rearrangement step and overcome the energy barrier to form fibrils. This delay in fibrillation and accumulation of nuclei at low temperature (25°C) result in a decrease in the mean length of the fibers when placed at 65°C. Fits of an empirical model to the data provide quantitative measures of the delay in the lag‐time during the nucleation process and subsequent reduction in fibril growth rate resulting from the cooling. Also, the seeding experiments, within the time‐scale of the measurements, demonstrate that fibers can initiate fast fibrillation with dissolved insulin (fresh or taken during the lag‐period) but not with other fibers. Qualitatively this is explained with a conjectual free‐energy space plot. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Automated scaffold selection for enzyme design
Authors: Malisi Christoph , Kohlbacher Oliver , Höcker Birte 
Published: March 2009

AbstractA major goal of computational protein design is the construction of novel functions on existing protein scaffolds. There the first question is which scaffold is suitable for a specific reaction. Given a set of catalytic residues and their spatial arrangement, one wants to identify a protein scaffold that can host this active site. Here, we present an algorithm called ScaffoldSelection that is able to rapidly search large sets of protein structures for potential attachment sites of an enzymatic motif. The method consists of two steps; it first identifies pairs of backbone positions in pocket‐like regions. Then, it combines these to complete attachment sites using a graph theoretical approach. Identified matches are assessed for their ability to accommodate the substrate or transition state. A representative set of structures from the Protein Data Bank (∼3500) was searched for backbone geometries that support the catalytic residues for 12 chemical reactions. Recapitulation of native active site geometries is used as a benchmark for the performance of the program. The native motif is identified in all 12 test cases, ranking it in the top percentile in 5 out of 12. The algorithm is fast and efficient, although dependent on the complexity of the motif. Comparisons to other methods show that ScaffoldSelection performs equally well in terms of accuracy and far better in terms of speed. Thus, ScaffoldSelection will aid future computational protein design experiments by preselecting protein scaffolds that are suitable for a specific reaction type and the introduction of a predefined amino acid motif. Proteins 2009. © 2009 Wiley‐Liss, Inc.
X‐ray vs. NMR structures as templates for computational protein design
Authors: Schneider Michael , Fu Xiaoran , Keating Amy E. 
Published: March 2009

AbstractCertain protein‐design calculations involve using an experimentally determined high‐resolution structure as a template to identify new sequences that can adopt the same fold. This approach has led to the successful design of many novel, well‐folded, native‐like proteins. Although any atomic‐resolution structure can serve as a template in such calculations, most successful designs have used high‐resolution crystal structures. Because there are many proteins for which crystal structures are not available, it is of interest whether nuclear magnetic resonance (NMR) templates are also appropriate. We have analyzed differences between using X‐ray and NMR templates in side‐chain repacking and design calculations. We assembled a database of 29 proteins for which both a high‐resolution X‐ray structure and an ensemble of NMR structures are available. Using these pairs, we compared the rotamericity, χ1‐angle recovery, and native‐sequence recovery of X‐ray and NMR templates. We carried out design using RosettaDesign on both types of templates, and compared the energies and packing qualities of the resulting structures. Overall, the X‐ray structures were better templates for use with Rosetta. However, for ∼20% of proteins, a member of the reported NMR ensemble gave rise to designs with similar properties. Re‐evaluating RosettaDesign structures with other energy functions indicated much smaller differences between the two types of templates. Ultimately, experiments are required to confirm the utility of particular X‐ray and NMR templates. But our data suggest that the lack of a high‐resolution X‐ray structure should not preclude attempts at computational design if an NMR ensemble is available. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Reliability behavior of GaN HEMTs related to Au diffusion at the Schottky interface
Authors: Jung Helmut , Behtash Reza , Thorpe James R. , Riepe Klaus , Bourgeois Franck , Blanck Hervé , Chuvilin Andrey , Kaiser Ute 
Published: March 2009

AbstractThe Schottky contact on GaN HEMT power devices is a key element for high power performance and its long term reliability behavior. Up to now such GaN devices are still suffering very often by a leakage current increase during operation resulting in deteriorated transistor behavior. One reason for this problem is owing to insufficiently stable Schottky contacts based on NiAu metalisation. We analysed GaN HEMTs with different aging behaviors by means of HR‐TEM and EDX investigations. It could be shown that on transistors with increasing leakage current Au was found directly on the Schottky interface which may be responsible for the increase of the leakage current. Furthermore, there are strong indications that such Au is diffusing via the gate foot side wall Ni‐SiN interface towards the Schottky barrier. It is proposed that an additional metallic diffusion barrier may solve this aging problem. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermodynamic dependences of slip length for nanofluidic flows over crystalline surfaces: Predictions of molecular theory of solvation
Authors: Kobryn Alexander E. , Ichiki Kengo , Kovalenko Andriy 
Published: March 2009

AbstractWe study the pressure and temperature dependence of the hydrodynamic slip length for the laminar flow of water near the crystalline surfaces of gold, copper, and nickel by the methods of nonequilibrium statistical mechanics. This study is further development of our previous work on formulation of the molecular theory of hydrodynamic (slip) boundary conditions in nanofluidics. Phenomenological picture relates slip length to viscosity of the liquid, and establishes the direct proportionality among them. Any difference between this phenomenological approach and measurements could not be explained, unless one uses the molecular theory of liquids and an appropriate atomistic model for surface corrugation. To vindicate the anomaly, we refer to the notion of formation and rupture of the hydrogen bond network in water. To verify this hypothesis, we apply the theory and perform calculations in the entire range of temperatures for the stable liquid phase and for pressures up to 100 MPa. The variation found in the slip length is of two orders of magnitude, which is much more than the variation in the viscosity alone. We validate our concept by referring to observable changes in the liquid microscopic structure and relating them with the theory. The information obtained is relevant for rational design of new MEMS/NEMS devices. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Modes of cooperative R&D commercialization by start‐ups
Authors: Aggarwal Vikas A. , Hsu David H. 
Published: March 2009

AbstractThis study empirically examines the determinants of heterogeneous firm‐level cooperative R&D commercialization strategies. While the volume of interfirm collaboration has increased dramatically in recent decades, the determinants of firm‐level choices among alternate modes of such cooperative activity remain relatively understudied. We develop a conceptual model of factors determining collaborative mode choice at the organizational portfolio level. These factors include the firm‐level appropriation environment, in which deal‐level choices have portfolio‐level spillover implications, as well as governance capabilities developed by the firm over time. Using a random sample of innovating biotechnology start‐ups, we assemble a firm‐year panel dataset that aggregates transaction‐level collaboration data to the firm‐year level, allowing us to characterize firms' portfolios of collaborative deals. We find broad empirical support for our model, suggesting that a firm's appropriation environment and governance capabilities strongly influence portfolio‐level collaboration mode choices. In addition, we explore the implications of governance capability development, finding that experience with particular modes, as well as deviations from existing capabilities, impact firm valuation. Copyright © 2009 John Wiley & Sons, Ltd.
Changes in mouse mu opioid receptor Exon 7/8‐like immunoreactivity following food restriction and food deprivation in rats
Authors: Hadjimarkou Maria M. , Abbadie Catherine , Kasselman Lora J. , Pan Ying‐xian , Pasternak Gavril W. , Bodnar Richard J. 
Published: March 2009

AbstractOpioid agonists and antagonists respectively increase and decrease food intake. That selective mu opioid antagonists are more effective than antisense probes directed against the mu opioid receptor (MOR‐1) gene in reducing deprivation‐induced feeding suggests a role for isoforms. Both food restriction and deprivation alter protein and mRNA levels of opioid peptides and receptors. Antisera directed against Exon 4 of the MOR‐1‐like immunoreactivity (LI) (Exon 4) clone or directed against mouse Exons 7/8 (mE7/8‐LI) revealed high levels of immunoreactivity in brain nuclei related to feeding behavior. Therefore, the present study assessed MOR‐1LI and mE7/8‐LI in hypothalamic and extrahypothalamic sites in rats exposed to ad libitum feeding, food restriction (2, 7, 14 days), or food deprivation (24, 48 h). MOR‐1‐LI displayed robust reactivity, but was insensitive to food restriction or deprivation. mE7/8‐LI, both in terms of cell counts and relative optical density, was significantly and selectively increased in the dorsal and ventral parvocellular subdivisions of the hypothalamic paraventricular nucleus in food‐restricted (14 days) rats, but all other restriction or deprivation regimens were ineffective in other hypothalamic nuclei. In contrast, significant and site‐specific decreases in relative optical density in the rostral part of the nucleus tractus solitarius (NTS) were observed in food‐restricted (2, 7 days) or food‐deprived (24, 48 h) animals, but these regimens were ineffective in the other extrahypothalamic sites. This study indicates the sensitivity of this mE7/8‐LI probe in the hypothalamic parvocellular paraventricular nucleus and rostral NTS to food restriction and deprivation in rats. Synapse 63:585–597, 2009. © 2009 Wiley‐Liss, Inc.
The Joule‐Thomson effect on the thermoelectric conductors
Authors: Consiglieri L. 
Published: March 2009

AbstractThe transmission of an electric current in a conductor is a process in which some electrical energy is converted into heat (thermal energy). We deal with a nonlinear boundary value elliptic problem which describes the electrical heating of a solid conductor and the Joule‐Thomson effect is taken into account. The existence of a weak solution is proved under both space and temperature dependence of the electrical and thermal conductivities. When the coefficients are only dependent on their temperature argument, some regularity results are stated.
An Unsupervised, Model-Free, Machine-Learning Combiner for Peptide Identifications from Tandem Mass Spectra
Authors: Edwards Nathan , Wu Xue , Tseng Chau-Wen 
Published: March 2009

Abstract
As the speed of mass spectrometers, sophistication of sample fractionation, and complexity of experimental designs increase, the volume of tandem mass spectra requiring reliable automated analysis continues to grow. Software tools that quickly, effectively, and robustly determine the peptide associated with each spectrum with high confidence are sorely needed. Currently available tools that postprocess the output of sequence-database search engines use three techniques to distinguish the correct peptide identifications from the incorrect: statistical significance re-estimation, supervised machine learning scoring and prediction, and combining or merging of search engine results. We present a unifying framework that encompasses each of these techniques in a single model-free machine-learning framework that can be trained in an unsupervised manner. The predictor is trained on the fly for each new set of search results without user intervention, making it robust for different instruments, search engines, and search engine parameters. We demonstrate the performance of the technique using mixtures of known proteins and by using shuffled databases to estimate false discovery rates, from data acquired on three different instruments with two different ionization technologies. We show that this approach outperforms machine-learning techniques applied to a single search engine’s output, and demonstrate that combining search engine results provides additional benefit. We show that the performance of the commercial Mascot tool can be bested by the machine-learning combination of two open-source tools X!Tandem and OMSSA, but that the use of all three search engines boosts performance further still. The Peptide identification Arbiter by Machine Learning (PepArML) unsupervised, model-free, combining framework can be easily extended to support an arbitrary number of additional searches, search engines, or specialized peptide–spectrum match metrics for each spectrum data set. PepArML is open-source and is available from http://peparml.sourceforge.net.
‘It Got Right to the Spot’ The Patient Experience of Primary Angioplasty: A Qualitative Study
Authors: Radcliffe Emma L. , Harding Geoffrey , Rothman Martin T. , Feder Gene S. 
Published: March 2009

Background: Primary angioplasty is becoming an established treatment for myocardial infarction. Yet we have a limited understanding of patients' attitudes toward this treatment and their experiences of receiving it in practice. Aims: Exploration of patients' experiences and perceptions of primary angioplasty as treatment for their heart attack. Methods: Qualitative study of a purposive sample of patients admitted to a tertiary cardiology unit in east London, UK. Participants were interviewed either in their own homes or in hospital. Recruitment continued until no new substantial themes emerged. Eleven men and four women aged 35 to 74 years who had sustained a myocardial infarction were interviewed 13 to 90 days after primary angioplasty. We used the framework method of analysis to identify and explore emerging themes. Results: Informants were expecting open-heart surgery as treatment for their heart attack. They were impressed by the service they actually received. They were generally not engaged in decisions about their treatment in the acute setting and this passivity sometimes persisted after discharge. Expectations of follow up in primary care were not often met. Conclusions: Patients are satisfied with the primary angioplasty as treatment for acute myocardial infarction but have poor understanding of the management of this condition.
Trans-nasal injection of botulinum toxin
Authors: Hussain A , Thiel G , Shakeel M 
Published: March 2009

AbstractIntroduction:Office-based laryngeal injection for the treatment of a variety of voice disorders is an established practice. Various methods of delivery to the vocal folds are in practice.Aim:We present a simple and repeatable method of injecting botulinum toxin into the larynx.Method:Botulinum toxin A (Botox®) was delivered into the larynx using a channelled fibre-optic laryngoscope under local anaesthetic, in an office setting.Results:Seven patients received regular botulinum toxin injections, via our preferred method. The treatment intervals and dosage regime varied depending on patient requirements. The procedure was carried out in an office setting, with minimal discomfort and inconvenience to the patient.Conclusion:We present a method of botulinum toxin delivery to the larynx which is simple, easily repeatable and simply learnt by the otolaryngologist familiar with fibre-optic laryngoscope usage. This method is also comfortable and convenient for the patient.
A prolonged outbreak ofSalmonellaTyphimurium infection related to an uncommon vehicle: hard cheese made from raw milk
Authors: VAN DUYNHOVEN Y. T. H. P. , ISKEN L. D. , BORGEN K. , BESSELSE M. , SOETHOUDT K. , HAITSMA O. , MULDER B. , NOTERMANS D. W. , De JONGE R. , KOCK P. , VAN PELT W. , STENVERS O. , VAN STEENBERGEN J. 
Published: March 2009

SUMMARYIn 2006, in The Netherlands, an outbreak ofSalmonellaTyphimurium phage type 561 (STM DT7, corresponding to the rare DT7 in the international typing scheme) was detected, accumulating to over 200 cases. By telephone interviews, data were collected from all laboratory-confirmed cases. In addition, in August 2006, a case-control study was performed in a subset of cases. Environmental and microbiological investigation was performed on a suspected dairy farm. In the case-control study (51 cases, 105 matched controls), hard cheese purchased from a farm, specifically farm X, and from a market stall were found to be associated with infection. The dairy production room of farm X tested STM DT7-positive in August. However, it was only in November, after earlier unsuccessful attempts, that a low-level contamination was confirmed in the hard farmhouse cheese, triggering control measures. A timely and adequate response was hampered during this outbreak for several reasons. Measures for improvement in handling future similar incidents are discussed.