bluuebunny/crossref_metadata_2025 huggingface dataset:
Unified finite element discretizations of coupled Darcy–Stokes flow
Authors: Karper Trygve , Mardal Kent‐Andre , Winther Ragnar
Published: May 2008

In this article, we discuss some new finite element methods for flows which are governed by the linear stationary Stokes system on one part of the domain and by a second order elliptic equation derived from Darcy's law in the rest of the domain, and where the solutions in the two domains are coupled by proper interface conditions. All the methods proposed here utilize the same finite element spaces on the entire domain. In particular, we show how the coupled problem can be solved by using standard Stokes elements like the MINI element or the Taylor–Hood element in the entire domain. Furthermore, for all the methods the handling of the interface conditions are straightforward. © 2008 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2009
Measuring blood pressure knowledge and self‐care behaviors of African Americans
Authors: Peters Rosalind M. , Templin Thomas N.
Published: May 2008

The purpose of this study was to develop and conduct preliminary psychometric assessment of instruments measuring knowledge and self‐care practices regarding behaviors needed for blood pressure (BP) control among African Americans. Items were empirically derived and scored on a 7‐point, bipolar scale. The instruments were evaluated in a sample of 306 community‐dwelling African Americans. Results revealed acceptable reliability and validity of the BP Knowledge Scale. Results for the BP Self‐Care Scale were mixed. A structural equation model of these scales, recorded BP, and covariates fit well. There was an unexpected positive correlation between self‐care and BP suggesting a potential bi‐directional relationship. The scales demonstrated acceptable psychometric properties and, with minor revisions, may have clinical utility as measures of BP knowledge and self‐care. © 2008 Wiley Periodicals, Inc. Res Nurs Health 31:543–552, 2008
The treatment of leprosy in 19th‐century London: a case study from St Marylebone cemetery
Authors: Walker D.
Published: May 2008

A young adult male, context [825], exhibiting a suite of proliferative and erosive skeletal changes, was excavated from the old burial ground of St Marylebone, London, in 2005 by the Museum of London Archaeology Service (MoLAS). Although pathognomonic rhinomaxillary changes were absent, a number of lesions were of a type previously recorded in individuals suffering from lepromatous leprosy, including resorption of the alveolar process of the maxillae and the digits of the right hand, osteomyelitis in the left ulna and collapse of the left ankle. Whilst this infectious disease was widespread in medieval Britain, it had declined by the 19th century, and has been identified in only one other post‐medieval archaeological context. The right leg of [825] had been surgically amputated. This form of intervention was a recognised treatment for the complications of the disease, where neuropathic damage of limbs led to life‐threatening infection. The healing of the amputation demonstrates the success of the operation, and the skill of the surgeon. Although the identity of the affected individual is unknown, burial within St Marylebone cemetery implies a level of status not frequently associated with leprosy sufferers in the past. Copyright © 2008 John Wiley & Sons, Ltd.
Coalition lobbying in Tanzania: the experiences of local NGOs
Authors: Elliott‐Teague Ginger L.
Published: May 2008

Among the few papers that have been written on interest group behaviour in developing countries, none considers how groups cooperate to influence public policy. This paper is intended to help fill that gap in the literature. It does so by comparing the formation and development of four non‐governmental organization (NGO) campaigns in Tanzania between 1997 and 2004. Three of these NGO campaigns were able to establish coalitions while one was not. The NGOs involved were attempting to influence public policy on three pieces of legislation: the Land Acts of 1999, the NGO Act of 2002 and the Environmental Management Act of 2004. Two theories of coalition formation, one of population ecology and one of resource dependency are used in the paper to assess their relevance to the Tanzanian experience. The paper finds that these theories do not adequately explain coalition formation in Tanzania.

Of several factors predicted by these theories, only two are found to be related to coalition formation in the Tanzanian case. However, when coalitions do form they allow individual groups to pool scarce resources, share information and expertise and enhance the legitimacy of the policy argument.

Copyright © 2008 John Wiley & Sons, Ltd.
The Epstein–Barr virus oncoprotein, latent membrane protein‐1, reprograms germinal centre B cells towards a Hodgkin's Reed–Sternberg‐like phenotype
Authors: Vockerodt M , Morgan SL , Kuo M , Wei W , Chukwuma MB , Arrand JR , Kube D , Gordon J , Young LS , Woodman CB , Murray PG
Published: May 2008

Although the latent membrane protein‐1 (LMP1) of the Epstein–Barr virus (EBV) is believed to be important for the transformation of germinal centre (GC) B cells, the precise contribution of this viral oncogene to lymphoma development is poorly understood. In this study, we used a non‐viral vector‐based method to express LMP1 in primary human GC B cells. Gene expression profiling revealed that LMP1 induced in GC B cells transcriptional changes characteristic of Hodgkin's lymphoma cell lines. Strikingly, LMP1 down‐regulated the expression of B‐cell‐specific genes including B‐cell receptor components such as CD79A, CD79B, CD19, CD20, CD22, and BLNK. LMP1 also induced the expression of ID2, a negative regulator of B‐cell differentiation. Our data suggest that in EBV‐positive cases, LMP1 is likely to be a major contributor to the altered transcriptional pattern characteristic of Hodgkin/Reed–Sternberg cells, including the loss of B‐cell identity. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Foetal death following lactic acidosis induced by ethanol, cocaine and metformin
Authors: Jones JB , McLellan D , McKenna K
Published: May 2008

A 33‐year‐old, 34‐week gestation patient with metformin treated gestational diabetes presented with lactic acidosis. Subsequent examination and ultrasound confirmed foetal death. Examination of the blood and urine provided evidence of ethanol and cocaine use on the day prior to admission.

Lactic acidosis has been reported after the use of metformin, but it is exceptionally rare. Precipitants such as ethanol and cocaine create a biochemically favourable environment in which lactic acidosis can occur. Therefore, in patients receiving metformin who have ingested such agents, lactic acidosis should be considered. Copyright © 2008 John Wiley & Sons.
Brainstorming in diabetes
Authors: Amiel SA
Published: May 2008

This lecture was given in memory of Dr Arnold Bloom to the 2008 Annual Professional Section Conference of Diabetes UK. In it, the author reviews insights gained by clinical research into the problems of hypoglycaemia unawareness in type 1 diabetes. Novel neuroimaging data suggest that a change in cortical responses to hypoglycaemia may be important to the syndrome of unawareness. Taking the neuroimaging methods into the study of people with insulin resistance suggests that an insulin responsive element of brain glucose metabolism is less insulin sensitive in people with peripheral insulin resistance, and that this ‘ central insulin resistance’ may be particularly evident in brain regions involved in appetite control and reward responses. The lecture concluded with an update of the UK islet transplant programme, now active for people with type 1 diabetes and intractable hypoglycaemia and also those with unstable glucose control after successful renal transplantation. Copyright © 2008 John Wiley & Sons.
Immunoproteomic identification of the hypothetical protein NMB1468 as a novel lipoprotein ubiquitous in Neisseria meningitidis with vaccine potential
Authors: Hsu Chi‐An , Lin Wei‐Ru , Li Jung‐Chen , Liu Yi‐Lung , Tseng Yen‐Tzu , Chang Chun‐Mien , Lee Yeong‐Sheng , Yang Chiou‐Ying
Published: May 2008

Many potential vaccine candidates for serogroup B Neisseria meningitidis (NMB) have been identified by reverse vaccinology, a genome‐based approach. However, some candidates may be unseen owing to uncertain annotation or their peculiar properties. In this study, we describe the preparation and identification of a novel lipoprotein expressed in all meningococcal strains tested. mAb were first prepared from mice immunized with a meningococcal B strain isolated in Taiwan. Total proteins from the immunizing strain were separated by 2‐DE in duplicate. Clone 4‐7‐3, which crossreacted to 174 tested meningococcal isolates, was used as the primary antibody for Western blotting. The immunoreactive spot was identified by LC‐mass spectrometric analysis of the corresponding spot from the silver‐stained gel and confirmed by molecular biology approach to be a novel lipoprotein encoded by the hypothetical NMB1468 gene. The potential use of this protein, designated Ag473/NMB1468, as a vaccine component was evaluated using the recombinant protein produced in Escherichia coli. Immunized mice were found to be protected from developing meningococcal disease after intraperitoneal inoculation with a lethal dose of meningococcal strain Nm22209, suggesting that Ag473/NMB1468 may be a promising vaccine candidate. This study also demonstrates the usefulness of the immunoproteomic approach in identification of novel vaccine candidates.
MAPRes: Mining association patterns among preferred amino acid residues in the vicinity of amino acids targeted for post‐translational modifications
Authors: Ahmad Ishtiaq , Qazi Wajahat M. , Khurshid Ahmed , Ahmad Munir , Hoessli Daniel C. , Khawaja Iffat , Choudhary M. Iqbal , Shakoori Abdul R. , Nasir‐ud‐Din
Published: May 2008

Post‐translational modification (PTM) of a protein is an important event in regulating cellular functions. An algorithm, MAPRes, has been developed for mining associations among PTM sites and the preferred amino acids in their vicinity. The algorithm has been implemented to O‐glycosylation and O‐phosphorylation data (phosphorylated/glycosylated Ser/Thr/Tyr). The association patterns mined by MAPRes demonstrate significant correlations and the results are in conformity with the existing methods. These association rules/patterns will be helpful in predicting the sequences/motifs involved for specific PTMs in proteins.
Proteomic map of peripheral blood mononuclear cells
Authors: Vergara Daniele , Chiriacò Fernanda , Acierno Raffaele , Maffia Michele
Published: May 2008

In the field of proteomics extensive efforts have been focused on the knowledge of proteins expressed by different cell types. In particular, enormous progress has been done in the characterization of blood cellular components. In this work, we have established a public 2‐DE database for human peripheral blood mononuclear cells (PBMCs) proteins. Two hundred and forty‐six spots corresponding to 174 different proteins have been identified on 2‐DE gels from PBMCs isolated from six healthy individuals. All the identified proteins have been classified in thirteen categories on the basis of their differential functions or cellular localization and annotated at the http://physiology.unile.it/proteomics. The role of several proteins has been discussed in relation to their biological function. We intend to show the potentiality of PBMCs to investigate the proteomics changes possibly associated with a large number of pathologies such as autoimmune, neurodegenerative and cancer diseases.
Aorta protein networks in marginal and acute zinc deficiency
Authors: Beattie John H. , Gordon Margaret‐Jane , Rucklidge Garry J. , Reid Martin D. , Duncan Gary J. , Horgan Graham W. , Cho Young‐Eun , Kwun In‐Sook
Published: May 2008

Human zinc deficiency is a global problem and may influence the development of cardiovascular disease. Our objective was to determine Zn deficiency affected pathways and protein interactions in rat aorta and their likely influence on stress‐induced atherogenesis. In two separate studies, rats were given diets acutely (<1 mg Zn/kg) or marginally (6 mg Zn/kg) deficient in Zn. Both studies included Zn adequate controls (35 mg Zn/kg) and the acute deficiency study included a pair‐fed group. After 6 wk, proteins from thoracic aorta were separated by 2‐DE. Proteins affected by zinc deficiency were identified by principal component analysis. Multiple correlations of identified proteins indicated protein networks of related function. Proteins clusters decreased in zinc deficiency were related to fatty acid and carbohydrate metabolism. Structurally related proteins, including zyxin and over nine transgelin 1 proteins, were either increased or decreased by acute and marginal deficiencies. PKCα was significantly decreased in Zn deficiency suggesting that Zn may regulate the phosphorylation of target proteins. Zn deficiency‐related changes in structural, carbohydrate and fatty acid‐related proteins may be disadvantageous for maintaining vascular health and are consistent with a protective role for zinc in the development of atherosclerosis.
Proteomic analysis of cellular protein alterations using a hepatitis B virus‐producing cellular model
Authors: Tong Aiping , Wu Lihong , Lin Qingsong , Lau Quek Choon , Zhao Xia , Li Jiong , Chen Ping , Chen Lijuan , Tang Hong , Huang Canhua , Wei Yu‐quan
Published: May 2008

Hepatitis B virus (HBV) is one of the major etiological factors responsible for acute and chronic liver disease and for the development of hepatocellular carcinoma (HCC). To determine the effects of HBV replication on host cell‐protein expression, we utilized 2‐DE and MS/MS analysis to compare and identify differentially expressed proteins between an HBV‐producing cell line HepG2.2.15 and its parental cell line HepG2. Of the 66 spots identified as differentially expressed (± over twofold, p <0.05) between the two cell lines, 62 spots (corresponding to 61 unique proteins) were positively identified by MS/MS analysis. These proteins could be clearly divided into three major groups by cluster and metabolic/signaling pathway analysis: proteins involved in retinol metabolism pathway, calcium ion‐binding proteins, and proteins associated with protein degradation pathways. Other proteins identified include those that function in diverse biological processes such as signal transduction, immune regulation, molecular chaperone, electron transport/redox regulation, cell proliferation/differentiation, and mRNA splicing. In summary, we profiled proteome alterations between HepG2.2.15 and HepG2 cells. The proteins identified in this study would be useful in revealing the mechanisms underlying HBV‐host cell interactions and the development of HCC. This study can also provide some useful clues for antiviral research.
Phosphoproteome analysis of the human Chang liver cells using SCX and a complementary mass spectrometric strategy
Authors: Sui Shaohui , Wang Jinglan , Yang Bing , Song Lina , Zhang Jiyang , Chen Ming , Liu Jinfeng , Lu Zhuang , Cai Yun , Chen Shuo , Bi Wei , Zhu Yunping , He Fuchu , Qian Xiaohong
Published: May 2008

The liver is the largest organ in the body, with many complex, essential functions, such as metabolism, deintoxication, and secretion, often regulated via post‐translational modifications, especially phosphorylation. Thus, the detection of phosphoproteins and phosphorylation sites is important to comprehensively explore human liver biological function. The human Chang liver cell line is among the first derived from non‐malignant tissue, and its phosphoproteome profile has never been globally analyzed. To develop the complete phosphoproteome and probe the roles of protein phosphorylation in normal human liver, we adopted a shotgun strategy based on strong cation exchange chromatograph, titanium dioxide and LC‐MS/MS to isolate and identify phosphorylated proteins. Two types of MS approach, Q‐TOF and IT, were used and compared to identify phosphosites from complex protein mixtures of these cells. A total of 1035 phosphorylation sites and 686 phosphorylated peptides were identified from 607 phosphoproteins. A search using the public database of PhosphoSite showed that approximately 344 phosphoproteins and 760 phosphorylation sites appeared to be novel. In addition, N‐terminal phosphorylated peptides were a greater fraction of all identified phosphopeptides. With GOfact analysis, we found that most of the identified phosphoproteins are involved in regulating metabolism, consistent with the liver's role as a key metabolic organ.
Identification of estrogen‐responsive proteins in MCF‐7 human breast cancer cells using label‐free quantitative proteomics
Authors: Zhu Zheying , Boobis Alan R. , Edwards Robert J.
Published: May 2008

17β‐Estradiol (E2) is a key regulatory steroid hormone that is involved in the control of a number of developmental and other functions. The aim of the present work was to identify estrogen‐dependent proteomic changes by determining the levels of expressed proteins in MCF‐7 human breast cancer cells following treatment with E2. A number of methods exist for differential analysis of complex proteomic mixtures. Here, a label‐free mass spectrometric approach comparing the ion intensities of tryptic peptides was adopted, which was combined with prefractionation of whole cell lysate proteins by 1‐D SDS‐PAGE. Using this approach, 60 proteins were found to be affected by E2. These comprised 55 up‐regulated and five down‐regulated proteins. These proteins varied widely in their physiochemical properties with pIs of 4–12 and molecular weights of 9–500 kDa. Pathway analysis revealed that the majority of changes were related and together describe an up‐regulated pathway consistent with the events of cell proliferation. The quantitative approach used here is relatively straightforward, avoids the use of costly labelling reagents, was reproducible within acceptable limits and has a linear response over a useful concentration range.
Comparison of two anoxia models in rainbow trout cells by a 2‐DE and MS/MS‐based proteome approach
Authors: Wulff Tune , Hoffmann Else K. , Roepstorff Peter , Jessen Flemming
Published: May 2008

In the literature, a variety of ways have been used to obtain anoxia, and most often results are compared between studies without taking into consideration how anoxia has been obtained. Here, we provide a comprehensive study of two types of anoxia, using a proteomics approach to compare changes in protein expression. The two investigated situations were 30 min of chemical anoxia (10 mM NaN3) followed by reoxygenation overnight (CR) and 2 h of N2‐induced anoxia (achieved by flushing with N2) followed by reoxygenation overnight (NR), after which samples were resolved by 2‐DE. Forty‐five protein spots changed their abundance in response to CR and 35 protein spots changed their abundance in response to NR, but only six proteins changed their abundance in response to both stimuli. By the means of MS/MS, 40 protein spots were identified including proteins involved in processes like cell protection and protein synthesis. It was also revealed that the level of a number of keratins was down‐regulated. This study therefore provides a valuable comparison of two different anoxia models and shows that great care should be taken when comparing the effects of anoxia in studies that have used different types and durations of anoxia.
Incorporating high‐throughput proteomics experiments into structural biology pipelines: Identification of the low‐hanging fruits
Authors: Pache Roland A. , Aloy Patrick
Published: May 2008

The last years have seen the emergence of many large‐scale proteomics initiatives that have identified thousands of new protein interactions and macromolecular assemblies. However, unfortunately, only a few among the discovered complexes meet the high‐quality standards required to be promptly used in structural studies. This has thus created an increasing gap between the number of known protein interactions and complexes and those for which a high‐resolution 3‐D structure is available. Here, we present and validate a computational strategy to distinguish those complexes found in high‐throughput affinity purification experiments that will stand the best chances to successfully express, purify and crystallize with little further intervention. Our method suggests that there are some 50 complexes recently discovered in yeast that could readily enter the structural biology pipelines.
Characterization of microRNA‐regulated protein‐protein interaction network
Authors: Hsu Chun‐Wei , Juan Hsueh‐Fen , Huang Hsuan‐Cheng
Published: May 2008

We have performed topological analysis to elucidate the global correlation between microRNA (miRNA) regulation and protein‐protein interaction network in human. The analysis showed that target genes of individual miRNA tend to be hubs and bottlenecks in the network. While proteins directly regulated by miRNA might not form a network module themselves, the miRNA‐target genes and their interacting neighbors jointly showed significantly higher modularity. Our findings shed light on how miRNA may regulate the protein interaction network.
Identification of differentially expressed proteins in Ficedula flycatchers
Authors: Buggiotti Laura , Primmer Craig R. , Kouvonen Petri , Bureš Stanislav , Corthals Garry L. , Leder Erica H.
Published: May 2008

This is the first report on the large‐scale identification and comparison of proteins in non‐model organisms, Ficedula flycatchers. It highlights the potential of proteomics approaches in both non‐sequenced and non‐model organisms for identification of differentially expressed proteins. Not surprisingly, more than 55% of the proteins failed to be identified even though the MS spectra were of high quality. Nevertheless, the protein information obtained in this study will serve as a valuable resource for continued research.
Quantitative analysis of Streptococcus pneumoniae TIGR4 response to in vitro iron restriction by 2‐D LC ESI MS/MS
Authors: Nanduri Bindu , Shah Pratik , Ramkumar Mahalingam , Allen Edward B. , Swiatlo Edwin , Burgess Shane C. , Lawrence Mark L.
Published: May 2008

Understanding the growth of bacterial pathogens in a micronutrient restricted host environment can identify potential virulence proteins that help overcome this nutritional barrier to productive infection. In this study, we investigated the pneumococcal protein expression response to iron limitation using an in vitro model. We identified S. pneumoniae TIGR4 proteins by 2‐D LC ESI MS/MS and determined significant changes in protein expression in response to iron restriction using computer‐intensive random resampling methods. Differential protein expression was studied in the context of a S. pneumoniae TIGR4 protein interaction network using Pathway Studio. Our analysis showed that pneumococcal iron restriction response was marked by increased expression of known virulence factors like PsaA. It involved changes in the expression of stress response, and phase variation and biofilm formation proteins. The net effect of changes in all these biological processes could increase the virulence of S. pneumoniae TIGR4 during in vivo infection.
Identification of novel substrates for Cdk5 and new targets for Cdk5 inhibitors using high‐density protein microarrays
Authors: Schnack Cathrin , Hengerer Bastian , Gillardon Frank
Published: May 2008

Cyclin‐dependent kinase (Cdk) 5 is a serine/threonine kinase that plays an important role during CNS development and its dysregulation is causally involved in the process of neuronal degeneration. To date more than 20 Cdk5 substrates have been identified and the number of Cdk5 substrates is still increasing. The different cellular functions of Cdk5 and its substrates are not completely known at present. High‐throughput protein microarray technology is a powerful tool to identify a large number of potential kinase substrates in parallel under the same experimental conditions. Using Protoarray protein microarrays we identified protein phosphatase 1, regulatory subunit 14A (PPP1R14A) as a novel substrate of Cdk5/p25. Phosphorylation was confirmed in two secondary assays. Our findings may contribute to the elucidation of the physiological function of Cdk5 in synaptic signalling. Functional Kinome Arrays were validated in a second set of experiments to characterize the selectivity of the Cdk5 inhibitor indolinone A. This lead to the identification of two additional kinases that are targeted by this compound and may provide a deeper understanding of its neuroprotective mode of action. However, several false negative results possibly due to a denatured or inactive conformation of the arrayed proteins, sound a note of caution when using protein array techniques.
Monitoring of changes in the membrane proteome during stationary phase adaptation of Bacillus subtilis using in vivo labeling techniques
Authors: Dreisbach Annette , Otto Andreas , Becher Dörte , Hammer Elke , Teumer Alexander , Gouw Joost W. , Hecker Michael , Völker Uwe
Published: May 2008

Bacillus subtilis has been developed as a model system for physiological proteomics. However, thus far these studies have mainly been limited to cytoplasmic, extracellular, and cell‐wall attached proteins. Although being certainly important for cell physiology, the membrane protein fraction has not been studied in comparable depth due to inaccessibility by traditional 2‐DE‐based workflows and limitations in reliable quantification. In this study, we now compare the potential of stable isotope labeling with amino acids (SILAC) and 14N/15N‐labeling for the analysis of bacterial membrane fractions in physiology‐driven proteomic studies. Using adaptation of B. subtilis to amino acid (lysine) and glucose starvation as proof of principle scenarios, we show that both approaches provide similarly valuable data for the quantification of bacterial membrane proteins. Even if labeling with stable amino acids allows a more straightforward analysis of data, the 14N/15N‐labeling has some advantages in general such as labeling of all amino acids and thereby increasing the number of peptides for quantification. Both, SILAC as well as 14N/15N‐labeling are compatible with 2‐DE, 2‐D LC‐MS/MS, and GeLC‐MS/MS and thus will allow comprehensive simultaneous interrogation of cytoplasmic and enriched membrane proteomes.
How broad band (from radio frequency to microwaves) dielectric parameters describe synthetic chemical reactions
Authors: Meyer Olivier , Delmotte Michel , Lacroix Jean‐Christophe , Weil Raphaël , Loupy André , Maurel François , Fourrier‐Lamer Arlette
Published: May 2008

Large differences in the dielectric responses of isolated molecules and associated reactive mixtures are observed over a wide frequency spectrum ranging from low to microwave frequencies. We present the results obtained for the curing (cross‐linking) of a resin mixed with a hardener. Electrical dipoles contribute to orientation polarization whose responses lie in the 1 kHz to over 1 GHz frequency range, which is predominantly higher than the 0.1 Hz–10 kHz range in which ionic conductivity is observed. It is the relaxation frequency of the reactive mixture that will be considered as the reaction marker. We also describe the results obtained with the saponification of an ester in the presence of a catalyst, with the reactive mixture containing – as in the previous case – electric dipoles and ions, but with responses superimposed in the 1 MHz–10 GHz frequency band. In this case, and for simplification reasons, the low frequency band ionic conductivity is the reaction marker. The aim of this paper is to translate synthetic chemical reactions into electronic terms, in order to allow electronics engineers to understand the interaction between electromagnetic waves and materials. Copyright © 2008 John Wiley & Sons, Ltd.
Waste‐free synthesis and production all across chemistry with the benefit of self‐assembled crystal packings
Authors: Kaupp Gerd
Published: May 2008

A systematic mechanistic discussion of solid‐state reactions (intracrystalline, intercrystalline, gas–solid thermal, or photochemical) at local molecular resolution is the basis for industrial sustainable production with waste‐free solid–gas and stoichiometric solid–solid reactions at low energy requirement. These profit from the bargain of the self‐assembled crystal packing. They rapidly complete to give 100% yield and require no solvent for workup. The basic requirements are thermodynamic feasibility and anisotropic molecular migrations at local pressure or suction in opposition to claims of ‘minimal atomic and molecular movements’ that do not know gas–solid and solid–solid reactions. Topochemical failures are settled on that experimental basis by atomic force microscopy (AFM), correlation with the crystal packing, scanning near field optical microscopy (SNOM), and nanoscratching. A general three‐step phase rebuilding mechanism is derived that provides directions for all experimental situations including stereoregular polymerizations. Heat control in gas–solid equipment and solid–solid small‐scale vibration or large‐scale rotation ball‐mills is essential. If AFM identifies (nano)liquids cooling is required. Also rare cases of surface passivation are detected by AFM. Molecular solid‐state chemistry and mechanochemistry are differentiated. Solid‐state techniques easily exclude moisture and are able to synthesize hitherto inaccessible compounds. Some of the latter are selected for discussion out of more than 1000 waste‐free solid‐state reactions in addition to already executed kg‐scale productions using reasonably inexpensive starting materials with promise for industrial applications and extensions. They cover salt formations, complexations, additions, eliminations, substitutions, esterifications, carboxylations, rearrangements, linear dimerizations, cycloreversions, cyclizations, ring openings, cascade reactions, and CC‐couplings (Knoevenagel, Michael, aminomethylation). Copyright © 2008 John Wiley & Sons, Ltd.
Excess polarizabilities upon the first dipole‐allowed excitation of some conjugated oligomers
Authors: Ye J. F. , Chen H. , Note R. , Mizuseki H. , Kawazoe Y.
Published: May 2008

This paper presents theoretical predictions for the excess polarizabilities upon excitation from the ground state to the first dipole‐allowed excited state (11Bu) of some conjugated oligomers. The excess polarizability was obtained by simulating the Stark shift, which was predicted by the time‐dependent density functional theory (TDDFT) with the hybrid Becke‐3 Lee–Yang–Parr (B3LYP) potential. The Stark shift in solution was simulated by employing the non‐equilibrium integral equation formalism polarizable continuum model (IEFPCM). All the model molecules considered in this study were fully optimized by the Hartree–Fock (HF) method and the density functional theory (DFT) with the B3LYP potential, respectively. For diphenylpolyenes, the excess polarizabilities displayed by the DFT/B3LYP‐optimized geometries are more reasonable than those displayed by the HF‐optimized geometries when compared with the experimental results. However, this feature is not clearly demonstrated by our results in the cases of oligo(phenylenevinylene)s (OPVs). Copyright © 2008 John Wiley & Sons, Ltd.
Preparation and characterization of polypyrrole/magnetite nanocomposites synthesized by in situ chemical oxidative polymerization
Authors: Yen Shiang‐Jie , Chen Erh‐Chiang , Chiang Ray‐Kuang , Wu Tzong‐Ming
Published: May 2008

This work describes the preparation and characterization of polypyrrole (PPy)/iron oxide nanocomposites fabricated from monodispersed iron oxide nanoparticles in the crystalline form of magnetite (Fe3O4) and PPy by in situ chemical oxidative polymerization. Two spherical nanoparticles of magnetite, such as 4 and 8 nm, served as cores were first dispersed in an aqueous solution with anionic surfactant sodium bis(2‐ethylhexyl) sulfosuccinate to form micelle/magnetite spherical templates that avoid the aggregation of magnetite nanoparticles during the further preparation of nanocomposites. The PPy/magnetite nanocomposites were then synthesized on the surface of the spherical templates. Structural and morphological analysis showed that the fabricated PPy/magnetite nanocomposites are core (magnetite)‐shell (PPy) structures. Morphology of the PPy/magnetite nanocomposites containing monodispersed 4‐nm magnetite nanoparticles shows a remarkable change from spherical to tube‐like structures as the content of nanoparticles increases from 12 to 24 wt %. Conductivities of these PPy/magnetite nanocomposites show significant enhancements when compared with those of PPy without magnetite nanoparticles, in particular the conductivities of 36 wt % PPy/magnetite nanocomposites with 4‐nm magnetite nanoparticles are about six times in magnitude higher than those of PPy without magnetite nanocomposites. These results suggest that the tube‐like structures of 36 wt % PPy/magnetite nanocomposites may be served as conducting network to enhance the conductivity of nanocomposites. The magnetic properties of 24 and 36 wt % PPy/magnetitenanocomposites show ferromagnetic behavior and supermagnetism, respectively. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1291–1300, 2008
Electrical strength in ramp voltage AC tests of LDPE and its nanocomposites with silica and fibrous and laminar silicates
Authors: Hoyos M. , García N. , Navarro R. , Dardano A. , Ratto A. , Guastavino F. , Tiemblo P.
Published: May 2008

The electrical strength of a set of LDPE micro and nanocomposites with silica, laminar silicates and fibrous silicates has been studied. A significant 60% increase of the breakdown electrical field is shown by the microsized microdispersed LDPE/montmorillonite composites while only a 20% increase is obtained with a nanosized laminar silicate. Nanosized nanodispersed composites of the spherical silica and fibrous silicate with LDPE show a lower increase of the breakdown electrical field. The data point scatter in repeated tests is very high in the case of the microcomposites, indicating strong morphological heterogeneity, while it is very low in the nanocomposites. This implies that these nanocomposites are remarkably defect‐free as regards electrically “weak” sites. An analysis of the crystalline structure, semicrystalline morphology and inorganic particle size and distribution evidences the importance of the role played not only by the inorganic particles but also by the semicrystalline morphology in the final dielectric performance of the composite. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1301–1311, 2008
Quantum carpets of a slightly relativistic particle
Authors: Marzoli I. , Kaplan A.E. , Saif F. , Schleich W.P.
Published: May 2008

We analyze the structures emerging in the spacetime representation of the probability density woven by a slightly relativistic particle caught in a one‐dimensional box. In particular, we evaluate the relativistic effects on the revival time and the specific changes produced in the intermode traces, which quantum carpets consist of. Moreover, we present a detailed mathematical analysis of such quantum carpets pursuing the approach of a kernel. Here we represent the probability distribution as a superposition of interfering Airy function‐type structures along straight world lines. We also show that this phenomenon can be enhanced by many orders of magnitude in semiconductors with narrow band‐gap (e.g. as in InSb) and small effective mass of the electron, whereby due to the strong nonparabolicity of the semiconductor conduction band, the electron energy vs momentum dispersion relation behaves in a pseudo‐relativistic way.
Inhibitory effects of nordihydroguaiaretic acid (NDGA) on the IGF‐1 receptor and androgen dependent growth of LAPC‐4 prostate cancer cells
Authors: Ryan Charles J. , Zavodovskaya Marianna , Youngren Jack F. , Campbell Michael , Diamond Marc , Jones Jeremy , Shiry Laura , Allan Geoffrey , Maddux Betty A. , Goldfine Ira D.
Published: May 2008

BACKGROUND

Nordihydroguaiaretic acid (NDGA) is an inhibitor of the IGF‐1 receptor (IGF‐1R) in breast and other cancers, and concomitantly inhibits tumor growth both in cultured cells and animals. The current study evaluates the effect of NDGA on the androgen‐stimulated growth of human prostate cancer cells.

METHODS

LAPC‐4 prostate cancer cells in tissue culture were androgen starved for 3 days, 1 nM dihydrotestosterone (DHT) and other androgens were then added for up to 7 days, and cell proliferation measured. IGF‐1R protein expression was measured by Western blot, and IGF‐1R mRNA expression by quantitative PCR. IGF‐1R receptor kinase activation was measured by ELISA.

RESULTS

After 7 days, LAPC‐4 growth was doubled by 1 nM DHT. NDGA had a rapid effect to inhibit IGF‐1R autophosphorylation induced by IGF‐1. DHT increased the expression of IGF‐1R protein and mRNA levels. Maximal IGF‐1R protein levels were observed 3 days after the addition of androgen. In addition, NDGA, at 10 µM or less, inhibited DHT‐induced proliferation in both cells grown in plates and cells grown in soft agar. Androgen receptor (AR) studies by FRET revealed that NDGA had no conformational effects on the AR in response to ligand.

CONCLUSIONS

NDGA blocks the DHT‐induced growth of LAPC‐4 prostate cancer cells by several mechanisms including rapid inhibition of the IGF‐1R kinase, and a dose‐dependent inhibition of androgen stimulation of IGF‐1R expression. Clinical studies of this agent will determine its efficacy in the setting of androgen‐dependent prostate cancer. Prostate 68: 1232–1240, 2008. © 2008 Wiley‐Liss, Inc.
Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations
Authors: Sun Jielin , Chang Bao‐Li , Isaacs Sarah D. , Wiley Kathleen E. , Wiklund Fredrik , Stattin Pär , Duggan David , Carpten John D. , Trock Bruce J. , Partin Alan W. , Walsh Patrick C. , Grönberg Henrik , Xu Jianfeng , Isaacs William B. , Zheng S. Lilly
Published: May 2008

BACKGROUND

A strong cumulative effect of five genetic variants and family history on prostate cancer risk was recently reported in a Swedish population (CAPS). We carried out this study to confirm the finding in two U.S. study populations and perform a combined analysis to obtain a more stable estimate of the odds ratio (OR) for prostate cancer.

METHODS

We evaluated three SNPs at 8q24 and one SNP each at 17q12 and 17q24.3 in two study populations in the U.S. The first was a hospital‐based case–control study population at Johns Hopkins Hospital (JHH), including 1,563 prostate cancer patients and 576 control subjects. The second was the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, including 1,172 prostate cancer patients and 1,157 control subjects.

RESULTS

We confirmed a cumulative effect of five risk variants on prostate cancer risk. Based on a total of 5,628 cases and 3,514 controls from JHH, CGEMS, and CAPS, men who carry any combination of 1, 2, 3, and 4 or more of these five risk variants have an estimated OR (95% CI) of 1.41 (1.20–1.67), 1.88 (1.59–2.22), 2.36 (1.95–2.85), and 3.80 (2.77–5.22) for prostate cancer, respectively, compared to men who do not have any of these five risk variants. When family history was included, the cumulative effect was stronger.

DISCUSSION

These results provide an important confirmation for the cumulative effect of five genetic risk variants on prostate cancer risk. The more stable OR estimates of the cumulative effect of these six risk factors are a major step toward individual risk characterization for this disease. Prostate 68:1257–1262, 2008. © 2008 Wiley‐Liss, Inc.
A novel method to map and compare protein–protein interactions in spherical viral capsids
Authors: Carrillo‐Tripp Mauricio , Brooks Charles L. , Reddy Vijay S.
Published: May 2008

Viral capsids are composed of multiple copies of one or a few chemically distinct capsid proteins and are mostly stabilized by inter subunit protein–protein interactions. There have been efforts to identify and analyze these protein–protein interactions, in terms of their extent and similarity, between the subunit interfaces related by quasi‐ and icosahedral symmetry. Here, we describe a new method to map quaternary interactions in spherical virus capsids onto polar angle space with respect to the icosahedral symmetry axes using azimuthal orthographic diagrams. This approach enables one to map the nonredundant interactions in a spherical virus capsid, irrespective of its size or triangulation number (T), onto the reference icosahedral asymmetric unit space. The resultant diagrams represent characteristic fingerprints of quaternary interactions of the respective capsids. Hence, they can be used as road maps of the protein–protein interactions to visualize the distribution and the density of the interactions. In addition, unlike the previous studies, the fingerprints of different capsids, when represented in a matrix form, can be compared with one another to quantitatively evaluate the similarity (S‐score) in the subunit environments and the associated protein–protein interactions. The S‐score selectively distinguishes the similarity, or lack of it, in the locations of the quaternary interactions as opposed to other well‐known structural similarity metrics (e.g., RMSD, TM‐score). Application of this method on a subset of T = 1 and T = 3 capsids suggests that S‐score values range between 1 and 0.6 for capsids that belong to the same virus family/genus; 0.6–0.3 for capsids from different families with the same T‐number and similar subunit fold; and <0.3 for comparisons of the dissimilar capsids that display different quaternary architectures (T‐numbers). Finally, the sequence conserved interface residues within a virus family, whose spatial locations were also conserved have been hypothesized as the essential residues for self‐assembly of the member virus capsids. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Interplay between structural rigidity and electrostatic interactions in the ligand binding domain of GluR2
Authors: Mamonova Tatyana , Speranskiy Kirill , Kurnikova Maria
Published: May 2008

Using molecular dynamics (MD) simulations, computational protein modifications, and a novel theoretical methodology that determines structural rigidity/flexibility (the FIRST algorithm), we investigate how molecular structure and dynamics of the glutamate receptor ligand binding domain (GluR2 S1S2) facilitate its conformational transition. S1S2 is a two‐lobe protein, which undergoes a cleft closure conformational transition upon binding an agonist in the cleft between the two lobes; hence it is expected that the mechanism of this conformational transition can be characterized as a hinge‐type. However, in the rigidity analysis one lobe of the protein is identified as a single rigid cluster while the other one is structurally flexible, inconsistent with a presumed mechanical hinge mechanism. Instead, we characterize the cleft‐closing transition as a load and lock mechanism. We find that when two cross‐cleft hydrogen bonds are disrupted the protein undergoes a rapid cleft opening transition. At the same time, the dynamical behavior of the cleft in the presence of the glutamate ligand is only weakly affected by the S652 peptide bond in its flipped conformation observed in the crystal structure. The residue E705 plays significant role in stabilization of the closed conformation via electrostatic interactions. The presence of the E705‐K730 salt bridge seems to correlate strongly withthe cleft opening transition in the MD simulations. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes
Authors: Martin Juliette , Regad Leslie , Etchebest Catherine , Camproux Anne‐Claude
Published: May 2008

Interresidue protein contacts in proteins structures and at protein–protein interface are classically described by the amino acid types of interacting residues and the local structural context of the contact, if any, is described using secondary structures. In this study, we present an alternate analysis of interresidue contact using local structures defined by the structural alphabet introduced by Camproux et al. This structural alphabet allows to describe a 3D structure as a sequence of prototype fragments called structural letters, of 27 different types. Each residue can then be assigned to a particular local structure, even in loop regions. The analysis of interresidue contacts within protein structures defined using Voronoï tessellations reveals that pairwise contact specificity is greater in terms of structural letters than amino acids. Using a simple heuristic based on specificity score comparison, we find that 74% of the long‐range contacts within protein structures are better described using structural letters than amino acid types. The investigation is extended to a set of protein–protein complexes, showing that the similar global rules apply as for intraprotein contacts, with 64% of the interprotein contacts best described by local structures. We then present an evaluation of pairing functions integrating structural letters to decoy scoring and show that some complexes could benefit from the use of structural letter‐based pairing functions. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Constitutive and dynamic phosphorylation and acetylation sites on NUCKS, a hypermodified nuclear protein, studied by quantitative proteomics
Authors: Wiśniewski Jacek R. , Zougman Alexandre , Krüger Sonja , Ziółkowski Piotr , Pudełko Marek , Bębenek Marek , Mann Matthias
Published: May 2008

Nuclear ubiquitous casein and cyclin‐dependent kinases substrate (NUCKS) is a 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as the structure of its DNA binding domain resembles that of high mobility group A (HMGA) proteins, chromosomal proteins known as modulators of chromatin conformation and regulators of transcription. Conformation and function of the HMGA proteins are regulated by phosphorylation and acetylation. So far 19 phosphorylation sites had been reported in NUCKS. In this study, we have identified all known and six additional phosphorylation sites, and also mapped multiple sites of acetylation, methylation and formylation. We measured cell cycle dependent changes of phosphorylation and acetylation of NUCKS in HeLa cells through stable isotope labeling by amino acids in cell culture (SILAC), using the dephosphorylated protein for normalization. We identified sites that were highly phosphorylated or dephosphorylated in mitotically arrested cells as well as sites that were constitutively phosphorylated. The extent of acetylation is reduced in mitotically and G1 arrested cells. Analysis of human cancer specimens revealed that in tissues the extent of acetylation, formylation and methylation is higher than in cultured cells. In breast cancer samples, seven acetylation, three methylation, and three formylation sites were mapped in NUCKS. Of the 243 amino acids, at least 36 can be modified with a total of 57 posttranslational modifications. Thus, NUCKS appears to have the highest ratio of modified to unmodified residues of any protein so far described. Proteins 2008. © 2008 Wiley‐Liss, Inc.