bluuebunny/crossref_metadata_2025 huggingface dataset:
LTCC‐based compact UWB antenna and its integration study
Authors: Sun Mei , Zhang Y. P.
Published: January 2008

A compact ultra‐wideband (UWB) antenna with size of 17 × 10 × 1 mm3 in low‐temperature co‐fired ceramic (LTCC) technology is designed, fabricated, and tested. It achieves impedance bandwidth of 6.7 GHz from 3.5 to 10.2 GHz. The measured antenna radiation patterns at 6.85 GHz are also presented. The antenna is further studied for a single‐package solution of UWB radio transceivers. The integration is analyzed with an emphasis on the connection of the antenna to the transceiver die. The final integrated UWB antenna has size of 20 × 10 × 1.2 mm3 and achieves impedance bandwidth of 6.7 GHz from 5.05 to 11.75 GHz with available radiation patterns. It also achieves the radiation efficiency of >96% and the gain of 2.5 to 4.3 dBi over the simulated UWB frequency range. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 789–793, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23209
Modified principle of distributed ferroelectric phase shifter considering the influence of interconnecting lines
Authors: Yu An , Yang Chuanren , Chen Hongwei , Zhang Jihua
Published: January 2008

The deviation between theoretic values and real data of distributed ferroelectric phase shifter is investigated by simulating an ideal model and analyzing an equivalent circuit. The deviation is shown to come from the parasitic inductance of interconnecting lines between loaded capacitors and center strip of CPW, which reduces the Bragg frequency, increases the insertion loss and phase shift. By introducing an effective capacitance to consider the effect of interconnecting lines, a modified principle is presented, which forecasts performances better. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 748–751, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23212
Impact of multiple tissue layers on an implantable LC sensor
Authors: Yvanoff Marie , Venkataraman Jayanti , Fuller Lynn
Published: January 2008

The impact of multiple tissue layers in a biotelemetry link consisting of a single loop antenna and an implantable LC sensor is investigated through simulation and measurements. The shift in resonant frequency due to the dispersive media encapsulating the sensor is analyzed. It is seen that the resonant frequency is strongly affected by the properties of the first layer, whereas additional layers prove to have little to no effect. Further, the capacitance values as well as the type of capacitor play a dominant role on the shift in the resonant frequency. It is demonstrated that smaller capacitance values would be required for determining the properties of the tissue region in which the sensor is embedded. The complexity of the multiple tissue layers is shown to be important in determining specific absorption rate (SAR) levels. An experimental validation has been done by immersing a LC sensor in single and multiple dispersive regions. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 783–787, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23216
Single and triple output coherence‐free microwave photonic filter using a 3 × 3 collinear coupler in a Sagnac fiber loop
Authors: Ning G. , Shum P. , Zhou J.
Published: January 2008

New structures that can realize single and triple output coherence‐free microwave photonic filter are presented. They are based on a Sagnac loop interferometer containing a single drive intensity modulator and a 3 × 3 collinear coupler, and no non‐reciprocal bias unit is required. Notch responses are obtained by modulating the clockwise and counterclockwise propagating waves inside the Sagnac loop at different times. Theoretical analysis is obtained for both DFB laser source and broad‐band source. Measured results verify the theoretical expressions and demonstrate robust notch filter responses. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 744–747, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23218
A novel crossed slotted patch dual‐mode bandpass filter with two transmission zeros
Authors: Wu Sean , Weng Min‐Hang , Jhong Shih‐Bin , Lee Maw‐Shung
Published: January 2008

This article presents a miniaturized dual‐mode bandpass filter (BPF) with two transmission zeros and low insertion‐loss using crossed slotted patch resonator. The BPF is mainly formed by a λ/2 patch resonator which is a pair of crossed slots with unequal widths is embedded in the center. By tuning the perturbation element, which resulted from the unequal slot widths along the diagonal, two resonant modes are excited and a pair of transmission zeros are generated to improve the selectivity of the BPF performance. The proposed filter at center frequency (f0) of 1.55 GHz has very good measured characteristics including the bandwidth of 1.49–1.62 GHz (3‐dB fractional bandwidth of 8.4%), low insertion loss of 1.74 ± 0.35 dB. The measured filter performance is in good agreement with the simulated response. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 741–744, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23219
Printed and double‐sided dipole array antennas with a parallel reflector
Authors: Huang Jhin‐Fang , Liang Jia‐Wei
Published: January 2008

This article describes the novel design of printed and doubled‐sided dipole array antennas with parallel reflector in the application of 2.4 GHz ISM band operated in WiFi access point. The printed dipole array antenna consists of one dipole array arranged back to back and can be easily formed by printing on both sides of a dielectric substrate and is suitable for integration with monolithic microwave integrated circuit (MMIC) module. Based on the matching theory, a 50 Ω microstrip feed line with open stub matched circuits is determined to possess high performance. The all extremely wideband or high gain dipole antenna array for value of standing wave ratio (VSWR) ≤ 1.5 has been successfully implemented and achieved. Simulator IE3D is used to verify our analysis. Both simulated and measured data are much identical. The designed 8‐element printed dipole array antenna without and with a reflector metallic ground plane achieves a gain of 8.5–9.3 dB with a 200 MHz bandwidth and a gain of 11.4–12.3 dB with a 80 MHz bandwidth, respectively. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 595–600, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23223
A comparison between two solution techniques to solve the equations of glacially induced deformation of an elastic Earth
Authors: Bängtsson Erik , Lund Björn
Published: January 2008

In this paper we compare two modeling frameworks within which we compute the Earth's elastic response to an external load. The main difference between the two frameworks lies in their capability to solve the partial differential equations (PDE) for a pre‐stressed elastic body, and especially how the term describing the pre‐stress advection is represented. Furthermore, the two frameworks differ in their applicability in the incompressible limit, the choice of the finite elements (FEs) used for the discretization, and the solution strategy for the arising algebraic problem.

The two frameworks are denoted as Framework I and II. Framework I is confined to the features of a commercial FE package (ABAQUS), whereas Framework II is based on a code developed by the authors.

The efficiency and accuracy of the two frameworks are compared via theoretical analysis and numerical experiments for two model problems in 2D and 3D. We find that the preconditioned iterative solution method used in Framework II is more efficient than the direct solver used in Framework I. Furthermore, we find that the solutions obtained from the two frameworks differ significantly for compressible solids. This is due to how the pre‐stress advection term is handled. Copyright © 2008 John Wiley & Sons, Ltd.
Modulation of multidrug resistance in cancer cells by the E3 ubiquitin ligase seven‐in‐absentia homologue 1
Authors: Liu M , Aneja R , Wang H , Sun L , Dong X , Huo L , Joshi HC , Zhou J
Published: January 2008

Seven‐in‐absentia homologue 1 (Siah1) is an E3 ubiquitin ligase that regulates the ubiquitination and proteasome‐dependent degradation of a number of proteins. Here we report that Siah1 modulates multidrug resistance 1 (MDR1)/P‐glycoprotein‐mediated drug resistance in the cancer cell lines examined. Siah1, but not its ligase‐dead mutant, down‐regulates MDR1/P‐glycoprotein and sensitizes the multidrug‐resistant cells to chemotherapeutic agents. Mechanistically, Siah1 does not promote P‐glycoprotein degradation but decreases its expression transcriptionally by promoting c‐Jun transcription factor binding to the activator protein 1 (AP1) site in the MDR1 promoter. Moreover, Siah1 triggers c‐Jun NH2‐terminal kinase (JNK) activation, leading to enhanced phosphorylation of c‐Jun, and the JNK/c‐Jun signalling axis is critical for Siah1 to down‐regulate MDR1/P‐glycoprotein expression. These findings demonstrate a previously unidentified role for Siah1 in regulating MDR1/P‐glycoprotein expression through the JNK/c‐Jun pathway. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Using prescription registries to define continuous drug use: how to fill gaps between prescriptions
Authors: Nielsen Lars Hougaard , Løkkegaard Ellen , Andreasen Anne Helms , Keiding Niels
Published: January 2008

Pharmacoepidemiological studies often use prescription registries to assess patients' drug episodes. The databases usually provide information on the date of the redemption of the prescription as well as on the dispensed amount, and this allows us to define episodes of drug use. However, when patients take less medication than prescribed, apparent gaps between prescriptions occur, and most studies handle this issue by allowing for small gaps when defining continuous drug use. This paper argues that it becomes crucial whether gaps are ‘filled’ prospectively or retrospectively. In the latter case the inferred exposure status depends on the patient's future dispensing behaviour and this can lead to severe bias in the findings of the study. In this paper we investigate this potential bias in a study of the risk of acute myocardial infarction (AMI) for women using hormone therapy (HT), and we show that the retrospective exposure definition introduces an artificially protective effect of HT. Copyright © 2008 John Wiley & Sons, Ltd.
Population‐based study of the effectiveness of bone‐specific drugs in reducing the risk of osteoporotic fracture
Authors: Perreault Sylvie , Dragomir Alice , Blais Lucie , Moride Yola , Rossignol Michel , Ste‐Marie Louis‐Georges , Fernandès Julio Cesar
Published: January 2008

Aim

Evidence supports bone‐specific drugs (BSDs) efficacy in the fracture risk reduction. But treatment rates for osteoporosis among high‐risk patients are far below the recommended guidelines. A major concern about BSDs is the lack of adherence with treatment.

Objective

To determine if BSDs decrease fracture risk in high‐risk elderly women in real clinical setting.

Methods

A nested case‐control design was used in a cohort of elderly women from the Quebec health databases. Women enter into the cohort if they are 70 years or older between 1995 and 2003. Nested case‐controls were designed for women with a diagnosis of osteoporosis (OP) and for those with a prior fracture. All cases of fractures occurring during follow‐up were matched with 10 randomly selected controls based on age, time period, bone mass density testing, and having a diagnosis of OP or a prior fracture. Use of BSDs before the index date was categorized as follows: short‐term (≤1 year), intermediate‐term (>1 and ≤ 3 years), and long‐term (>3 years). We used an adjusted conditional logistic regression model to assess BSD effect on fracture.

Results

Among 3170 women who had a fracture, of these women, 1824 had OP and 1346 had a prior fracture. Only long‐term exposure to BSDs among women with OP reduced the fracture risk by 16% (odds ratio: 0.84; 0.73–0.97). Among women with OP, a high number of medical services or use of anticonvulsants or narcotics increased the fracture risk by 12–73%. Among women with a prior fracture, a high number of medical services or risk of fall or use of benzodiazepines, antidepressants, or narcotics increased the fracture risk by 23–77%.

Conclusion

The incidence of fractures decreased by 16% among women with OP when more than 80% of BSDs was used for at least 3 years. Among women with a prior fracture, fracture risk reduction was not significant. Exposure to BSDs among women with a prior fracture is troubling, given that only approximately 12% of these individuals were being treated, and only 2% was using BSDs for the long term. Copyright © 2008 John Wiley & Sons, Ltd.
Terminal proteomics: N‐ and C‐terminal analyses for high‐fidelity identification of proteins using MS
Authors: Nakazawa Takashi , Yamaguchi Minoru , Okamura Taka‐aki , Ando Eiji , Nishimura Osamu , Tsunasawa Susumu
Published: January 2008

In proteomics, MS plays an essential role in identifying and quantifying proteins. To characterize mature target proteins from living cells, candidate proteins are often analyzed with PMF and MS/MS ion search methods in combination with computational search routines based on bioinformatics. In contrast to shotgun proteomics, which is widely used to identify proteins, proteomics based on the analysis of N‐ and C‐terminal amino acid sequences (terminal proteomics) should render higher fidelity results because of the high information content of terminal sequence and potentially high throughput of the method not requiring very high sequence coverage to be achieved by extensive sequencing. In line with this expectation, we review recent advances in methods for N‐ and C‐terminal amino acid sequencing of proteins. This review focuses mainly on the methods of N‐ and C‐terminal analyses based on MALDI‐TOF MS for its easy accessibility, with several complementary approaches using LC/MS/MS. We also describe problems associated with MS and possible remedies, including chemical and enzymatic procedures to enhance the fidelity of these methods.
Retracted: Mitochondria, the missing link between body and soul: Proteomic prospective evidence
Authors: Warda Mohamad , Han Jin
Published: January 2008

Retraction: The following article from the journal PROTEOMICS, 'Mitochondria, the missing link between body and soul: Proteomic perspective evidence' by Mohamad Warda and Jin Han, published online on 23 January 2008 in Wiley InterScience (www.interscience.wiley.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Michael J. Dunn and the publisher Wiley‐VCH. The retraction has been agreed due a substantial overlap of the content of this article with previously published articles in other journals.

PROTEOMICS apologizes to our readership.
The role of IL‐6 and IL‐11 in hyperoxic injury in developing lung
Authors: Chetty Anne , Cao Gong‐Jee , Manzo Nicholas , Nielsen Heber C , Waxman Aaron
Published: January 2008

We examined the cytoprotective effect of interleukin‐6 (IL‐6) and interleukin‐11 (IL‐11) during oxidant injury in neonatal lung and the regulators of cell death in vitro and in vivo after oxidant exposure. Type II cells from day 21 fetal neonatal rat lungs were treated with varying concentrations of either IL‐6 or IL‐11 for 24 hr prior to exposure to H2O2. Three‐day‐old transgenic lung‐specific IL‐11 and IL‐6 overexpressing and wild type (WT) mouse pups were exposed to hyperoxia or room air for 3 days. Type II cells exposed to either IL‐6 or IL‐11 prior to oxidant injury exhibited improved survival compared to controls, 67% ± 2.6 survivals in IL‐6 pretreated cells compared to 48% ± 1.6 in control; 63% ± 3 survivals in IL‐11 pretreated cells compared to 49% ± 2.6 in control. The number of TUNEL positive cells in hyperoxia‐exposed lungs was increased compared to room air animals (27 ± 0.9 vs. 4 ± 0.4; mean ± SEM; P < 0.05). In contrast, the number of TUNEL positive cells was reduced in hyperoxia‐exposed lungs from IL‐11 (+) mice (15.2 ± 2.2; mean ± SEM; P < 0.05). There was an enhanced accumulation of Bcl‐2 and reduction of Bax protein in hyperoxia‐exposed IL‐11 (+) compared to room air‐exposed mice. This was not seen in hyperoxia‐exposed IL‐6 (+) pups. An increase in caspase‐3 was seen in hyperoxia‐exposed lungs of WT pups compared to IL‐11 (+) pups. IL‐11 and IL‐6 provide protective effects against oxidant‐mediated injury in fetal type II cells and IL‐11 provides protection in vivo by down‐regulation of caspase‐mediated cell death. Pediatr Pulmonol. 2008; 43:297–304. © 2008 Wiley‐Liss, Inc.
Helix formation is a dynamical bottleneck in the recovery reaction of Photoactive Yellow Protein
Authors: Vreede Jocelyne , Hellingwerf Klaas J. , Bolhuis Peter G.
Published: January 2008

The bacterial sensor Photoactive Yellow Protein (PYP) signals the presence of blue light by undergoing a series of conformational changes. We present atomistic Parallel Tempering (Replica Exchange Molecular Dynamics) simulations of conformational changes occurring during the photo‐cycle of PYP. First, we study the signaling state formation of PYP in detail. Our previous simulations have shown that the formation of the signaling state is characterized by the solvent exposure of both the chromophore and Glu46 (Vreede J, Crielaard W, Hellingwerf KJ, Bolhuis PG. Biophys J, 2005;8:3525–3535). Subsequent NMR results agreed with this prediction, but as these experiments were performed on an N‐terminally truncated mutant, a simulation of this mutant would further substantiate our previous results. Here, we compare simulations of the truncated PYP to the NMR structures, as well as to the wild type predictions. This comparison also gives some insight into the role of the N‐terminal domain of PYP, which restricts the movement of the chromophore binding pocket (CBP) in the wild type. Second, we report simulations of the recovery of the receptor state from the signaling state. While we did not observe complete refolding of the protein, we did observe transient interactions between residues of the CBP occurring when the chromophore is in a trans configuration. Using simulations that sample anomalous exposure of the chromophore in the receptor state, we were able to sample chromophore re‐entry into its binding pocket. While the involved time scales prohibit drawing definitive conclusions even when using parallel tempering, we nevertheless propose that the formation of a helix in the CBP is essential for a successful recovery of the receptor state, and forms a kinetic barrier in this process. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Analysis and prediction of protein local structure based on structure alphabets
Authors: Dong Qiwen , Wang Xiaolong , Lin Lei , Wang Yadong
Published: January 2008

In recent years, protein structure prediction using local structure information has made great progress. Many fragment libraries or structure alphabets have been developed. In this study, the entropies and correlations of local structures are first calculated. The results show that neighboring local structures are strongly correlated. Then, a dual‐layer model has been designed for protein local structure prediction. The position‐specific score matrix, generated by PSI‐BLAST, is inputted to the first‐layer classifier, whose output is further enhanced by a second‐layer classifier. The neural network is selected as the classifier. Two structure alphabets are explored, which are represented in Cartesian coordinate space and in torsion angles space respectively. Testing on the nonredundant dataset shows that the dual‐layer model is an efficient method for protein local structure prediction. TheQ‐scores are 0.456 and 0.585 for the two structure alphabets, which is a significant improvement in comparison with related works. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Computational active site analysis of molecular pathways to improve functional classification of enzymes
Authors: Ozyurt A. Sinem , Selby Thomas L.
Published: January 2008

This study describes a method to computationally assess the function of homologous enzymes through small molecule binding interaction energy. Three experimentally determined X‐ray structures and four enzyme models from ornithine cyclo‐deaminase, alanine dehydrogenase, and mu‐crystallin were used in combination with nine small molecules to derive a function score (FS) for each enzyme‐model combination. While energy values varied for a single molecule‐enzyme combination due to differences in the active sites, we observe that the binding energies for the entire pathway were proportional for each set of small molecules investigated. This proportionality of energies for a reaction pathway appears to be dependent on the amino acids in the active site and their direct interactions with the small molecules, which allows a function score (FS) to be calculated to assess the specificity of each enzyme. Potential of mean force (PMF) calculations were used to obtain the energies, and the resulting FS values demonstrate that a measurement of function may be obtained using differences between these PMF values. Additionally, limitations of this method are discussed based on: (a) larger substrates with significant conformational flexibility; (b) low homology enzymes; and (c) open active sites. This method should be useful in accurately predicting specificity for single enzymes that have multiple steps in their reactions and in high throughput computational methods to accurately annotate uncharacterized proteins based on active site interaction analysis. Proteins 2008. © 2008 Wiley‐Liss, Inc.
The insecticidal protein hirsutellin A from the mite fungal pathogen Hirsutella thompsonii is a ribotoxin
Authors: Herrero‐Galán Elías , Lacadena Javier , Martínez del Pozo Álvaro , Boucias Drion G. , Olmo Nieves , Oñaderra Mercedes , Gavilanes José G.
Published: January 2008

The mite fungal pathogen Hirsutella thompsonii produces a single polypeptide chain, insecticidal protein named hirsutellin A (HtA) that is composed of 130 amino acid residues. This protein has been purified from its natural source and produced as a recombinant protein in Escherichia coli. Spectroscopic analysis has determined that the two protein forms are indistinguishable. HtA specifically inactivates ribosomes and produces the α‐fragment characteristic of ribotoxin activity on rRNA. Behaving as a cyclizing ribonuclease, HtA specifically cleaves oligonucleotides that mimick the sarcin/ricin loop of the ribosome, as well as selected polynucleotides and dinucleosides. HtA interacts with phospholipid membranes as do other ribotoxins. As a consequence of its ribonuclease activity and its ability to interact with cell membranes, HtA exhibits cytotoxic activity on human tumor cells. On the basis of these results, HtA is considered to be a member of the ribotoxin group of proteins, although it is significantly smaller (130 aa) than all known ribotoxins that are composed of 149/150 amino acids. Ribotoxins are members of a larger family of fungal ribonucleases whose members of smaller size (100/110 aa) are not cytotoxic. Thus, the characterization of the fungal ribotoxin HtA represents an important milestone in the study of the diversity and the function of fungal ribonucleases. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Unfolding and aggregation of transthyretin by the truncation of 50 N‐terminal amino acids
Authors: Mizuguchi Mineyuki , Hayashi Ayumi , Takeuchi Makoto , Dobashi Mizuki , Mori Yoshihiro , Shinoda Hiroyuki , Aizawa Tomoyasu , Demura Makoto , Kawano Keiichi
Published: January 2008

Senile systemic amyloidosis (SSA) is caused by amyloid deposits of wild‐type transthyretin in various organs. Amyloid deposits from SSA contain large amounts of the C‐terminal fragments starting near amino acid residue 50 as well as full‐length transthyretin. Although a number of previous studies suggest the importance of the C‐terminal fragments in the pathogenesis of SSA, little is known about the structure and aggregation properties of the C‐terminal fragments of transthyretin. To understand the role of C‐terminal fragments in SSA, we examined the effects of the truncation of the N‐terminal portions on the structure and aggregation properties of wild‐type transthyretin. The deletion mutant lacking 50 N‐terminal residues was largely unfolded in terms of secondary and tertiary structure, leading to self‐assembly into spherical aggregations under nearly physiological conditions. By contrast, the deletion mutant lacking 37 N‐terminal residues did not have a strong tendency to aggregate, although it also adopted a largely unfolded conformation. These results suggest that global unfolding of transthyretin by proteolysis near amino acid residue 50 is an important step of self‐assembly into aggregations in SSA. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Acidic range titration of HEWL using a constant‐pH molecular dynamics method
Authors: Machuqueiro Miguel , Baptista António M.
Published: January 2008

In this work, we present the first application to a protein of the stochastic constant‐pH molecular dynamics (MD) method with the inclusion of proton tautomerism. The acidic titration of HEWL was performed under different conditions. Both generalized reaction field (GRF) and particle mesh Ewald (PME) methods were used in the treatment of the long range electrostatics and, even though the PME simulations revealed to be more stable, the better results were obtained using GRF (pKa RMSD of 0.82 for GRF and 1.13 for PME). The results using PME at different dielectric constants (2, 4, and 8) also revealed that there was no significant improvement in pKa's prediction upon increasing the dielectric constant. The secondary structure analysis of HEWL revealed a remarkably stable protein in the acidic pH range. The β‐sheet strands (unlike the α‐helices) seem to be destabilized upon pH decrease, suggesting that the β‐domain is less stable than the α‐domain. The four principal α‐helices were also ordered according to their stability in the acidic pH range and the results (4 < 1 < 2 ≈ 3) were consistent with the ones obtained in thermal denaturation studies. Proteins 2008. © 2008 Wiley‐Liss, Inc.
How to lose a kink and gain a helix: pH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers
Authors: Jang Hyunbum , Michaud‐Agrawal Naveen , Johnston Jennifer M. , Woolf Thomas B.
Published: January 2008

We have simulated two conformations of the fusion domain of influenza hemagglutinin (HA) within explicit water, salt, and heterogeneous lipid bilayers composed of POPC:POPG (4:1). Each conformation has seven different starting points in which the initial peptide structure is the same for each conformation, but the location across the membrane normal and lipid arrangement around the peptide are varied, giving a combined total simulation time of 140 ns. For the HA5 conformation (primary structure from recent NMR spectroscopy at pH = 5), the peptide exhibits a stable and less kinked structure in the lipid bilayer compared to that from the NMR studies. The relative fusogenic behavior of the different conformations has been investigated by calculation of the relative free energy of insertion into the hydrophobic region of lipid bilayer as a function of the depth of immersion. For the HA7 conformations (primary structure from recent NMR spectroscopy at pH = 7.4), while the N‐terminal helix preserves its initial structure, the flexible C‐terminal chain produces a transient helical motif inside the lipid bilayer. This conformational change is pH‐independent, and is closely related to the peptide insertion into the lipid bilayer. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Prediction of protein local structures and folding fragments based on building‐block library
Authors: Dong Qiwen , Wang Xiaolong , Lin Lei
Published: January 2008

In recent years, protein structure prediction using local structure information has made great progress. In this study, a novel and effective method is developed to predict the local structure and the folding fragments of proteins. First, the proteins with known structures are split into fragments. Second, these fragments, represented by dihedrals, are clustered to produce the building blocks (BBs). Third, an efficient machine learning method is used to predict the local structures of proteins from sequence profiles. Finally, a bi‐gram model, trained by an iterated algorithm, is introduced to simulate the interactions of these BBs. For test proteins, the building‐block lattice is constructed, which contains all the folding fragments of the proteins. The local structures and the optimal fragments are then obtained by the dynamic programming algorithm. The experiment is performed on a subset of the PDB database with sequence identity less than 25%. The results show that the performance of the method is better than the method that uses only sequence information. When multiple paths are returned, the average classification accuracy of local structures is 72.27% and the average prediction accuracy of local structures is 67.72%, which is a significant improvement in comparison with previous studies. The method can predict not only the local structures but also the folding fragments of proteins. This work is helpful for the ab initio protein structure prediction and especially, the understanding of the folding process of proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Method for comparing the structures of protein ligand‐binding sites and application for predicting protein–drug interactions
Authors: Minai Ryoichi , Matsuo Yo , Onuki Hiroyuki , Hirota Hiroshi
Published: January 2008

Many drugs, even ones that are designed to act selectively on a target protein, bind unintended proteins. These unintended bindings can explain side effects or indicate additional mechanisms for a drug's medicinal properties. Structural similarity between binding sites is one of the reasons for binding to multiple targets. We developed a method for the structural alignment of atoms in the solvent‐accessible surface of proteins that uses similarities in the local atomic environment, and carried out all‐against‐all structural comparisons for 48,347 potential ligand‐binding regions from a nonredundant protein structure subset (nrPDB, provided by NCBI). The relationships between the similarity of ligand‐binding regions and the similarity of the global structures of the proteins containing the binding regions were examined. We found 10,403 known ligand‐binding region pairs whose structures were similar despite having different global folds. Of these, we detected 281 region pairs that had similar ligands with similar binding modes. These proteins are good examples of convergent evolution. In addition, we found a significant correlation between Z‐score of structural similarity and true positive rate of “active” entries in the PubChem BioAssay database. Moreover, we confirmed the interaction between ibuprofen and a new target, porcine pancreatic elastase, by NMR experiment. Finally, we used this method to predict new drug–target protein interactions. We obtained 540 predictions for 105 drugs (e.g., captopril, lovastatin, flurbiprofen, metyrapone, and salicylic acid), and calculated the binding affinities using AutoDock simulation. The results of these structural comparisons are available at http://www.tsurumi.yokohama‐cu.ac.jp/fold/database.html Proteins 2008. © 2008 Wiley‐Liss, Inc.
Comparative structural analysis of the binding domain of follicle stimulating hormone receptor
Authors: Fan Qing R. , Hendrickson Wayne A.
Published: January 2008

Proteins with leucine‐rich repeats (LRRs) specialize in mediating protein–protein interactions. The hormone binding portion of the receptor for follicle stimulating hormone (FSH) is an LRR protein by sequence, and the crystal structure of this domain from human FSH receptor in a complex with FSH shows that it does indeed have an LRR structure. It differs from other LRR domains, however, in being an all‐β protein composed of highly irregular repeats and having only slight overall curvature. Despite these distinctions and a superficial resemblance to β‐helical proteins, the binding domain of FSH receptor clearly is an LRR protein. The structure does consist of two parts with distinctively different curvatures. Comparison with the structures of other LRR‐containing proteins shows a correlation between curvature and main‐chain hydrogen bonding pattern of the parallel β‐sheet. The hormone‐binding site is located at the concave surface of the receptor structure, a feature common to proteins with LRR motifs. Analysis of the ligand‐binding site of LRR‐containing proteins reveals that they generally utilize extensive interface area and a large number of charged residues to facilitate high‐affinity protein‐protein interactions. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Rigid body essential X‐ray crystallography: Distinguishing the bend and twist of glutamate receptor ligand binding domains
Authors: Bjerrum Esben J. , Biggin Philip C.
Published: January 2008

The ligand‐binding domain (LBD) from the ionotropic glutamate receptor subtype 2 (GluR2) has been shown to adopt a range of ligand‐dependent conformational states. These states have been described in terms of the rotation required to fit subdomain (lobe) 2 following superposition of subdomain (lobe) 1. The LBD has a closed‐cleft conformation for full agonists, but partial agonists induce a range of closure, which in turn controls the open probability of discrete subconductance states in the full‐length receptor. Although this description is useful, it may not account for all physiologically important motions that the receptor undergoes. We have used an approach that combines the methods of essential dynamics and rigid‐body dynamics to analyze 124 monomer domains from 55 crystal structures of the GluR2 LBD. We are able to show that partial agonists also induce a significant amount of twist that would not be anticipated using one rotational descriptor between apo and full‐agonist‐bound states. Furthermore, one of the crystal structures (chain B from 1P1U, the GluR2 L650T‐AMPA complex), which has been suggested to represent an agonist‐bound inactive form of the receptor, lies at the extreme of this twist motion. We suggest that partial agonists not only prevent full closure but also move the receptor closer to this inactive state. We demonstrate additionally how the method can be used to compare the results of molecular dynamics simulations with the crystallographic data and the extent to which the conformational space explored by both overlaps. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Protein kinase C isozymes and their selectivity towards ruboxistaurin
Authors: Tang Sishi , Xiao Victor , Wei Lianhu , Whiteside Catharine I. , Kotra Lakshmi P.
Published: January 2008

Protein kinase C (PKC) isozymes are an important class of enzymes in cell signaling and as drug targets. They are involved in specific pathways and have selectivity towards certain ligands, despite their high sequence similarities. Ruboxistaurin is a specific inhibitor of PKC‐β. To understand the molecular determinants for the selectivity of ruboxistaurin, we derived the three‐dimensional structures of the kinase domains of PKC‐α, ‐βI, and ‐ζ using homology modeling. Several binding orientations of ruboxistaurin in the binding sites of these PKC catalytic domains were analyzed, and a putative alternative binding site for PKC‐ζ was identified in its kinase domain. The calculated free energy of binding correlates well with the IC50 of the inhibitor against each PKC isozyme. A residue‐based energy decomposition analysis attributed the binding free energy to several key residues in the catalytic sites of these enzymes, revealing potential protein–ligand interactions responsible for ligand binding. The contiguous binding site revealed in the catalytic domain of PKC‐ζ provides avenues for selective drug design. The details of structural nuances for specific inhibition of PKC isozymes are presented in the context of the three‐dimensional structures of this important class of enzymes. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Structural insight into the distinct properties of copper transport by the Helicobacter pylori CopP protein
Authors: Park Sung Jean , Jung Yu‐Sun , Kim Ji‐Sun , Seo Min‐Duk , Lee Bong Jin
Published: January 2008

Helicobacter pylori CopP (HpCopP) is a putative copper binding regulatory protein composed of 66 amino acid residues. The small HpCopP protein is homologous to CopZ, encoded by the E. hirae and B. subtilis cop operons. To clarify the role of HpCopP in copper metabolism in H. pylori, we studied the structural and copper binding characteristics by NMR spectroscopy. Based on the resonance assignments, the tertiary structure of HpCopP was determined. Unlike the βαββαβ fold of the homologous CopZ, HpCopP adopts the βαββα fold. The superposition with structures of other bacterial copper binding proteins showed that the global structure of HpCopP follows the general topology of the family, regardless of absence of the C‐terminal β‐strand. The Cu(I) binding property of HpCopP was well conserved like CopZs: the structural changes due to Cu(I) and Ag(I) bindings were primarily restricted to the metal binding motif (CXXC motif). On the other hand, the Cu(II) binding property of CopP was different with that of CopZ: in the absence of reducing agent, Cu(II) ion oxidized a mutant HpCopP, resulting in disulfide bond formation in the CXXC motif. The Cu(II) ion binding property was evaluated using the mutant HpCopP, in which two amino acids were artificially introduced at the C‐terminus, since the reduced state of the CXXC motif was more stabile in the mutant HpCopP without a reducing agent. Here, the structure and copper binding property of HpCopP are discussed in detail. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Synthesis and sst2 binding profiles of new [Tyr3]octreotate analogs
Authors: Petrou Christos , Magafa Vassiliki , Nikolopoulou Anastasia , Pairas George , Nock Berthold , Maina Theodosia , Cordopatis Paul
Published: January 2008

One of the main objectives of our current work is the development of new somatostatin analogs that would retain the general characteristics of [Tyr3]octreotate (Tate) while showing potential for clinical application. In this respect, study of their interaction with the sst2 is crucial in providing preliminary structure‐activity relationships data. In the present work we report on the synthesis and the preliminary biological evaluation of a total of 15 new structurally modified [Tyr3]octreotate analogs. The binding affinities were determined during competition binding assays in sst2‐positive rat acinar pancreatic AR4‐2J cell membranes using [125I‐Tyr3]octreotide as the radioligand. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Structure of cubic polytype indium nitride layers on top of modified sapphire substrates
Authors: Morales F. M. , Lozano J. G. , García R. , Lebedev V. , Wang Ch. Y. , Cimalla V. , Ambacher O. , González D.
Published: January 2008

The cover picture of this issue of physica status solidi (c) has been taken from the article [1].
Development and application of an autonomous unmanned aerial vehicle for precise aerobiological sampling above agricultural fields
Authors: Schmale III David G. , Dingus Benjamin R. , Reinholtz Charles
Published: January 2008

Remote‐controlled (RC) unmanned aerial vehicles (UAVs) have been used to study the movement of agricultural threat agents (e.g., plant and animal pathogens, invasive weeds, and exotic insects) above crop fields, but these RC UAVs are operated entirely by a ground‐based pilot and often demonstrate large fluctuations in sampling height, sampling pattern, and sampling speed. In this paper, we describe the development and application of an autonomous UAV for precise aerobiological sampling tens to hundreds of meters above agricultural fields. We equipped a Senior Telemaster UAV with four aerobiological sampling devices and a MicroPilot‐based autonomous system, and we conducted 25 sampling flights for potential agricultural threat agents at Virginia Tech's Kentland Farm. To determine the most appropriate sampling path for aerobiological sampling above crop fields with an autonomous UAV, we explored five different sampling patterns, including multiple global positioning system (GPS) waypoints plotted over a variety of spatial scales. An orbital sampling pattern around a single GPS waypoint exhibited high positional accuracy and produced altitude standard deviations ranging from 1.6 to 2.8 m. Autonomous UAVs have the potential to extend the range of aerobiological sampling, improve positional accuracy of sampling paths, and enable coordinated flight with multiple UAVs sampling at different altitudes. © 2008 Wiley Periodicals, Inc.
Investigation of metal‐induced crystallization in amorphous Ge/crystalline Al bilayers by Auger microanalysis and selected‐area depth profiling
Authors: Wang Z. M. , Wang J. Y. , Jeurgens L. P. H. , Mittemeijer E. J.
Published: January 2008

The diffusion processes and accompanying microstructural changes occurring in amorphous Ge (a‐Ge)/crystalline Al bilayers upon annealing have been investigated by using a combined approach of Auger microanalysis, selected‐area depth profiling (SA‐DPR), scanning electron microscopy (SEM) and X‐ray diffraction. Upon annealing at 150 °C for 10 min, the partially crystallized Al/a‐Ge (with the Al layer at the top) and a‐Ge/Al (with the a‐Ge layer at the top) specimens show reacted and unreacted regions with a lateral size of ∼1–2 µm at their surfaces. SA‐DPR at the location of unreacted regions at the surface shows that at such locations the original Al/a‐Ge (or a‐Ge/Al) bilayer structure is almost preserved. On the other hand, depth profiling at the location of reacted regions shows that at such locations the original a‐Ge sublayer had fully crystallized and contains 10–20 at.% Al, and that in the original Al sublayer, crystalline Ge (c‐Ge) had formed at the Al grain boundaries (GBs). These observations could be explained in consequence of the initiation of crystallization of a‐Ge at the Al GBs followed by the nucleation of crystallization at the a‐Ge/Al interface, as supported by thermodynamic calculations of interface energetics. Copyright © 2008 John Wiley & Sons, Ltd.
Analysis of grain boundaries in an embrittled ancient silver necklace
Authors: Vaníčková Jaroslava , Děd Jiří , Bartuška Pavel , Drahokoupil Jan , Čerňanský Marian , Lejček Pavel
Published: January 2008

Archaeological silver objects are often found to be embrittled to some extent. Using light and scanning electron microscopy techniques, X‐ray diffraction and AES, the causes of this embrittlement were studied on a silver artefact buried for more than 1000 years in soil. This investigation revealed the presence of chlorine, sulphur and carbon at grain boundaries of the Ag–Cu based object suggesting that most likely; the substantial embrittlement is caused by an inter‐crystalline corrosion attack. The role of copper enrichment at the grain boundaries as a possible path of preferential corrosion attack is discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Quantification of surface excitation effects on the EPES‐determined IMFPs for GaN and SiC
Authors: Krawczyk Miroslaw
Published: January 2008

Surface electron inelastic excitations, a consequence of electron surface interaction, effect substantially the measured peak intensities, or peak areas, in surface‐sensitive electron spectroscopies, and distort the quantitative information. To obtain reliable quantitative information from the electron spectra, the measured intensities and/or peak areas should be corrected for these effects.

In the present work, we investigated, quantitatively, the influence of surface excitations on electron inelastic mean free paths (IMFPs) determined by elastic peak electron spectroscopy (EPES). We used IMFPs obtained from the previous EPES measurements of the electron elastic backscattering probability for GaN, SiC, and the Ni standard in the energy range 200–2000 eV. Calculated surface excitation parameters (SEPs) of both incident and emitted electrons were evaluated using the formulae of Chen, Tu et al., and Werner et al., and applied for correcting the EPES IMFPs. These corrected values were compared with those predicted by the TPP‐2M formula.

We found that implementation of the surface excitation correction improved agreement between the resulting IMFPs for selected wide‐band semiconductors and the TPP‐2M values. The extent to which the IMFPs measured by EPES differ from the corresponding bulk values (on account of surface excitations) was found to depend on the semiconductor material with finite surface. The results also clearly demonstrated the importance of accounting for surface excitations for accuracy of the measured IMFPs. Copyright © 2008 John Wiley & Sons, Ltd.
Investigation of thin oxide films on titanium for capacitor applications
Authors: Schroth S. , Schneider M. , Mayer ‐ Uhma T. , Michaelis A. , Klemm V.
Published: January 2008

Thin passive films on titanium formed by electrolytic oxidation show a high relative permittivity and could be a promising cost effective dielectric material for capacitor applications. In the present work, the films were formed in an acetate buffer solution by potentiodynamic polarisation up to various potentials. The film thickness was determined by coulometry and ellipsometry. The growth factor is 2.7 nm/V. Furthermore, by using an electrochemical micro‐capillary cell the anodising process was performed at high lateral resolution on different substrate grains with various crystallographic orientations. An influence of the Ti grain orientation on the TiO2 film thickness could not be observed under the used experimental conditions. By means of transmission electron microscope(TEM) investigation the oxide film structure could be determined as prevailing amorphous. Copyright © 2008 John Wiley & Sons, Ltd.
Exploiting Enzymatic (Reversed) Hydrolysis in Directed Self‐Assembly of Peptide Nanostructures
Authors: Das Apurba K. , Collins Richard , Ulijn Rein V.
Published: January 2008

Enzyme‐catalyzed reactions can be exploited to control molecular self‐assembly under physiological conditions by converting nonassembling precursors into self‐assembly building blocks. Two complementary approaches based on aromatic short‐peptide derivatives that form molecular hydrogels are demonstrated. Firstly, it is shown that esterase‐directed self assembly via hydrolysis of hydrophobic N‐(fluorenyl‐9‐methoxycarbonyl) (Fmoc)‐peptide methyl esters give rise to formation of transparent hydrogels composed of defined peptide nanotubes. The internal and external diameters of these tubes are highly tunable, depending on the amino acid composition and chain length of the building blocks. Secondly, protease‐directed self‐assembly of Fmoc‐peptide esters is achieved via amide‐bond formation (reversed hydrolysis) for combinations of Fmoc‐threonine and leucine/phenylalanine methyl esters, producing fibrous hydrogels. Upon treatment with an esterase, these systems revert back to solution, thus providing a two‐stage solution–gel–solution transition.