bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Drug Delivery: Pharmacokinetic Considerations, Methods and Systems
Authors: Zuo Zhong , Lee Vincent H. L.
Published: March 2008

Controlled drug delivery applies interdisciplinary approaches to engineer systems that improve the therapeutic value of drugs. This review addresses the biological basis of drug delivery, the pharmacokinetic/pharmacodynamic considerations important to the design of controlled release delivery systems, and the methods to fabricate them. The focus of this review will principally be on oral and transdermal applications. Systems at various stages of development for the delivery of more complex molecules, such as proteins, oligonucleotides, genes, and sRNA's will also be discussed.
Molecular Recognition: Computational Analysis and Modelling
Authors: Feldman‐Salit Anna , Wade Rebecca C.
Published: March 2008

Molecular recognition is critical to many fundamental processes in biology, including enzymatic reactions, signal transduction, genetic information processing, as well as molecular and cellular transport. The question of how proteins selectively recognize and correctly associate with their partners is an active research problem. For many proteins, experimental information about the structures of their molecular complexes and the details of their interactions are lacking. Macromolecular, structure‐based computational techniques provide a means to predict the interactions of proteins and to investigate their recognition mechanisms. Here, we first discuss the general mechanism of molecular recognition as a multistep process from diffusion of one molecule toward the second to tight complex formation. We then describe the main forces and the physical properties that govern biomolecular interactions and introduce the principles of modeling them. Finally, simulation methods and computational approaches for molecular docking are briefly presented.
Inositol Phospholipids: Biosynthesis and Biological Functions
Authors: Bruzik Karol S.
Published: March 2008

Phosphatidylinositol phosphates are cellular signaling molecules that came to prominence in the mid‐1980s, after inositol trisphosphate was discovered as a key intracellular second messenger generated from phosphatidylinositol 4,5‐bisphosphate in response to stimulation of a wide range of extra‐cellular receptors. Since then, many novel inositol phosphates and phospholipids have been discovered, and their cellular functions have been studied. The roles of these molecules encompass regulation of many processes indispensable to organism homeostasis. On the cellular level, the processes include regulation of cell growth and differentiation, cell motility and invasiveness, vesicular trafficking, protein targeting to specific cell compartments. This review focuses on biosynthesis and biological roles of phosphatidylinositol phospholipids.
Systems Approach to Studying Disease
Authors: Foltz Gregory D. , Hood Leroy
Published: March 2008

The emerging field of systems biology promises to transform our understanding of the molecular basis of human disease. Recent technological advances allow for multiparameter measurements to be integrated across global genomic and proteomic platforms to inform predictive and probabilistic gene and protein regulatory networks. A systems approach to disease is based on the idea that disease‐perturbed gene and protein regulatory networks differ from their normal counterparts, and that these differences are predictive of the disease course and response to therapy. The ability to detect disease‐related perturbations in individual patients will transform health care over the next decade from our current reactive medicine to a new medical practice that is predictive, personalized, preventive, and participatory (P4 medicine).
Practical Synthesis of (E)‐α,β‐Unsaturated Carboxylic Acids Using a One‐Pot Hydroformylation/Decarboxylative Knoevenagel Reaction Sequence
Authors: Kemme Susanne T. , Šmejkal Tomáš , Breit Bernhard
Published: March 2008

Combining the regioselective room temperature/ambient pressure hydroformylation and a modification of the Doebner–Knoevenagel reaction allowed for the development of an efficient, one‐pot procedure for the synthesis of (E)‐α,β‐unsaturated carboxylic acids. The reaction proceeds under mild conditions, tolerates a variety of functional groups and gives (E)‐α,β‐unsaturated carboxylic acids in good yields and with excellent regio‐ and stereocontrol. The practicability of this process has been demonstrated by a short protecting group‐free synthesis of the queen honeybee pheromones 9‐ODA [(E)‐9‐oxodec‐2‐enoic acid] and 9‐HDA [(E)‐9‐hydroxydec‐2‐enoic acid].
Cloning, expression, and localization of a molt‐related β‐N‐acetylglucosaminidase in the spruce budworm, Choristoneura fumiferana
Authors: Zheng Y.‐P. , Krell P.J. , Doucet D. , Arif B.M. , Feng Q.‐L.
Published: March 2008

A β‐N‐acetylglucosaminidase cDNA (CfGlcNAcase) was cloned from the spruce budworm, Choristoneura fumiferana. Western blotting analysis of developmental CfGlcNAcase expression revealed high levels of expression of the gene on the last day of the 5th instar larvae and the first day in the 6th instar larvae, followed by a decrease to background levels during the intermolt of the 6th instar. CfGlcNAcase was detected again from the last day of the 6th instar to day 2 of pupal stage. CfGlcNAcase expression was induced by tebufenozide at 24 h post treatment and remained at high levels until 72 h. Immunohistochemical localization analysis of CfGlcNAcase indicated that CfGlcNAcase was present in the molting fluid, epidermis, trachea, and hemolymph in prepupae during the transformation from larva to pupa. CfGlcNAcase cDNA was expressed into a recombinant protein in bacterial and baculovirus systems and the protein expressed in the baculovirus system had a higher chitinolytic activity than in the bacterial system and appeared to be secreted. Arch. Insect Biochem. Physiol. 2008. © 2008 Wiley‐Liss, Inc.
Efficient Synthesis of Symmetrically and Unsymmetrically Substituted Hexaphenylbenzene Analogues by Suzuki–Miyaura Coupling Reactions
Authors: Yang Xiaoyin , Dou Xi , Müllen Klaus
Published: March 2008

A series of symmetrically and unsymmetrically substituted hexaphenylbenzene (HPB) analogues were efficiently synthesized by using a sterically hindered Suzuki–Miyaura cross‐coupling reaction of arylboronic acids with 1,4‐diiodo‐2,3,5,6‐tetraarylbenzenes under our optimized reaction conditions. The 1,4‐diiodo‐2,3,5,6‐tetraarylbenzenes can be readily prepared by using a one‐pot Hart reaction. Oxidative cyclodehydrogenation of the dibromo derivative with FeCl3 gave the corresponding hexabenzocoronene (HBC) derivative in good yield.
TROSY effects in MAS solid‐state NMR
Authors: Chevelkov Veniamin , Reif Bernd
Published: March 2008

Use of transverse relaxation‐optimized spectroscopy (TROSY) type techniques had a dramatic impact on the study of large proteins with a molecular weight >30kDa for solution‐state NMR. In the solid‐state, such an effect would not be expected a prior, as the investigated molecules are immobilized. However, local motions induce fluctuations of the local fields experienced by the nuclear spins and, this way, are effective for relaxation. We demonstrate that protein dynamics can significantly influence the resonance line width in ultra high resolution MAS (magic angle spinning) solid‐state NMR experiments. Averaging of the 15NHα/β multiplet components as a consequence of 1H decoupling induces effective broadening of the 15N resonance. Application of TROSY type techniques that select only the narrow component of the multiplet pattern results in an increased resolution and, thus, will be of benefit for MAS solid‐state NMR spectroscopy. © 2008 Wiley Periodicals, Inc. Concepts Magn Reson Part A 32A: 143–156, 2008.
A Water‐Stable and Strongly Luminescent Terbium(III) Macrocyclic Complex Incorporating an Intracyclic Pyrazolylpyridine Chromophore
Authors: Nasso Isabelle , Bedel Sébastien , Galaup Chantal , Picard Claude
Published: March 2008

A 15‐membered macrocyclic ligand L1H3 was designed with the aim of sensitizing the visible luminescence of the TbIII ion in water: this octadentate chelating ligand is based on an intracyclic N,C‐pyrazolylpyridine chromophore and a diethylenetriaminetriacetic acid core. This ligand reacts with equimolar amounts of LnCl3 salts to yield water‐soluble and stable complexes of the general formula [L1·Ln(H2O)]0. Detailed photophysical studies were performed in aerated water on the free ligand and its GdIII complex and complexes formed with LnIII ions commonly used in fluoroimmunoassays (Ln = Sm, Eu, Tb, and Dy). The results show a wide range in the emission properties of the complexes, which can be rationalized in terms of the chromophore triplet‐state energy. In particular, the TbIII complex has a remarkable overall quantum yield of ca. 50 % in H2O (80 % in D2O) and an energy‐transfer efficiency from sensitizer to the terbium ion of ca. 85 %. According to these results and in view of its kinetic inertness in aqueous solutions, the L1·Tb complex may be considered as a very promising candidate as long‐lived luminescent label for bioaffinity assays. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Enantiocontrolled Preparation of the First Stable α‐Ferrocenylalanine Derivatives
Authors: Moreno Rosa M. , Catasús Mònica , López Concepción , Moyano Albert
Published: March 2008

An enantiocontrolled synthesis of α‐ferrocenylalanine methyl ester (S)‐24 and of the corresponding N‐Boc derivative (S)‐25 is presented. We have found that an important source of instability for α‐ferrocenyl‐α‐amino acid derivatives is the high reactivity of the α‐hydrogen, and its replacement by a methyl group has proven to be essential for the stability of these compounds. The synthesis of (S)‐24 requires only six steps from the readily available 2‐propenylferrocene which is converted into the diol (S)‐16 by Sharpless catalytic dihydroxylation. Regio‐ and stereoselective azide substitution of the tertiary hydroxy group affords the azido diol (S)‐17. Swern oxidation gives the corresponding aldehyde which is smoothly oxidized to the carboxylic ester by means of the Smith–Kozlowski protocol. Transesterification and azide reduction lead to the α‐amino ester (S)‐24 in a good overall yield and enantiomeric purity. A cyclic voltammetric study of this compound showed that oxidation takes place by a simple reversible one‐electron‐transfer process. Half a century after the initial unsuccessful attempts to obtain ferrocenylglycine, this is the first synthesis of a stable α‐amino acid derivative incorporating a ferrocene unit at the α‐position.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Development of Prototype Wireless Transmission Measurement for Glucose in Subcutaneous and Brain Striatum
Authors: Ahmad Farook , Chow Fook Cheong , Ho Yah Wen , Chin Yew Siang , Christenson Andreas , Bainbridge Martina , Md Yusof Ahmad Pauzi , Ab Ghani Sulaiman
Published: March 2008

Monitoring of glucose in subcutaneous and brain striatum have been extensively studied in the past. While biocompatibility was one of the limitations, others included the messy measuring equipments preclude monitoring in a complex environment. This study tried to establish an amperometric measurement of glucose in pre‐ and post‐insulin‐administration on diabetic and hyperglycemia rats via wireless. The results have indicated that the wireless sensing kit used was capable of monitoring glucose in both subcutaneous and brain. The physiological data have also shown a new insight on the fabrication of implantable glucose sensors.
Al(III) and Fe(III) Balance in Hemodialysis Treatment Assessed via Fluid Analysis by Adsorptive Stripping Voltammetry and UV Sample Digestion
Authors: Nascimento Paulo C. , Del‐Fabro Luciana D. , Bohrer Denise , de Carvalho Leandro M. , Rosa Marcelo B. , Noremberg Simone M.
Published: March 2008

Simultaneous determination of Al(III) and Fe(III) in posthemodialysis fluids was investigated by the Adsorptive stripping voltammetry of solochrome violet metal complexes. The adsorption of the complexes on the mercury electrode (HMDE) was investigated by out of phase altenating current voltammetry in presence of the main matrix interfering species. Sample digestion by UV irradiation was investigated to overcome the matrix interference. The proposed method was valid for real posthemodialysis samples containing or not Desferrioxamine B. Detection limits of 1.4 and 1.8 μg L−1 were calculated for Al(III) and Fe(III), respectively. Recoveries ranging from 88.1 to 106.3% were obtained from spiking experiments.
Developmental differences of neurocognitive networks for phonological and semantic processing in Chinese word reading
Authors: Cao Fan , Peng Danling , Liu Li , Jin Zhen , Fan Ning , Deng Yuan , Booth James R.
Published: March 2008

Developmental differences in the neurocognitive networks for phonological and semantic processing in Chinese word reading were examined in 13 adults and 13 children using functional magnetic resonance imaging (fMRI). Rhyming and semantic association judgments were made to two‐character words that were presented sequentially in the visual modality. These lexical tasks were compared with a nonlinguistic control task involving judgment of line patterns. The first main finding was that adults showed greater activation than children in right middle occipital gyrus on both the meaning and rhyming task, suggesting adults more effectively engage right hemisphere brain regions involved in the visual‐spatial analysis of Chinese characters. The second main finding was that adults showed greater activation than children in left inferior parietal lobule for the rhyming as compared with the meaning task, suggesting greater specialization of phonological processing in adults. The third main finding was that children who had better performance in the rhyming task on characters with conflicting orthographic and phonological information relative to characters with nonconflicting information showed greater activation in left middle frontal gyrus, suggesting greater engagement of brain regions involved in the integration of orthography and phonology. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
The role of viral and bacterial pathogens in gastrointestinal cancer
Authors: Selgrad Michael , Malfertheiner Peter , Fini Lucia , Goel Ajay , Boland C. Richard , Ricciardiello Luigi
Published: March 2008

The association of Helicobacter pylori (H. pylori) with gastric cancer is thus far the best understood model to comprehend the causal relationship between a microbial pathogen and cancer in the human gastrointestinal tract. Besides H. pylori, a variety of other pathogens are now being recognized as potential carcinogens in different settings of human cancer. In this context, viral causes of human cancers are central to the issue since these account for 10–20% of cancers worldwide. In the case of H. pylori and gastric cancer, as well as the human papillomavirus and anal cancer, the causal relationship between the infectious agent and the related cancer in the gastrointestinal tract has been clearly confirmed by epidemiological and experimental studies. Similarly, Epstein–Barr virus and the oncogenic JC virus are being suggested as possible causative agents for cancers in the upper and lower gastrointestinal tract. This review discusses various viral and microbial pathogens and their oncogenic properties in the evolution of gastrointestinal carcinogenesis and summarizes the available experimental data make a convincing agreement favoring the associations between infectious agents and specific human cancers. J. Cell. Physiol. 216: 378–388, 2008. © 2008 Wiley‐Liss, Inc.
P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K‐ras mutations
Authors: Mahdavinia Mahboobeh , Bishehsari Faraz , Verginelli Fabio , Cumashi Albana , Lattanzio Rossano , Sotoudeh Masoud , Ansari Reza , Semeraro Daniela , Hormazdi Mahshid , Fakheri Hafez , Rakhshani Naser , De Lellis Laura , Curia Maria Cristina , Cama Alessandro , Piantelli Mauro , Malekzadeh Reza , Iacobelli Stefano , Mariani‐Costantini Renato
Published: March 2008

CRC‐associated P53 mutations have not been studied extensively in non‐Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin‐embedded CRC cases from Northern Iran for mutations in P53 exons 5–8 using PCR‐direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K‐ras mutations and high‐level microsatellite instability (MSI‐H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI‐H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non‐mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K‐ras transversions. Transitions at non‐CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K‐ras transitions and MSI‐H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI‐H were as reported for non‐Iranian patients. However P53 mutation site/type and correlations between P53 and K‐ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran. J. Cell. Physiol. 216: 543–550, 2008. © 2008 Wiley‐Liss, Inc.
Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva
Authors: Balci‐Peynircioglu Banu , Waite Andrea L. , Hu Chunbo , Richards Neil , Staubach‐Grosse Ann , Yilmaz Engin , Gumucio Deborah L.
Published: March 2008

Mutations in pyrin cause the autoinflammatory disorder familial Mediterranean fever (FMF), a syndrome characterized by sporadic and unpredictable attacks of fever and localized severe pain. Currently, it is not clear how attacks are triggered, nor why they spontaneously resolve after 2 or 3 days. In fact, the cellular function of the pyrin protein and the molecular underpinnings of its malfunction in FMF have so far eluded clear definition. The identification of pyrin‐interacting proteins has the potential to increase our understanding of the cellular networks in which pyrin functions. Previous reports have established that pyrin interacts with the apoptotic protein ASC, the cytoskeletal adaptor protein PSTPIP1, the inflammatory caspase, Caspase‐1 and certain forms of the cytosolic anchoring protein 14‐3‐3. Here, we report that pyrin also interacts with Siva, a pro‐apoptotic protein first identified for its interaction with the cytosolic tail of CD27, a TNF family receptor. The interaction between pyrin and Siva involves the C‐terminal B30.2/rfp/SRPY domain of pyrin and exon 1 of Siva. We show that Siva and pyrin are indeed co‐expressed in human neutrophils, monocytes, and synovial cells. Furthermore, using a novel protein/protein interaction assay, we demonstrate that pyrin can recruit Siva to ASC specks, establishing a potential platform for intersection of ASC and Siva function. Finally, we show that pyrin modulates the apoptotic response to oxidative stress mediated by Siva. Thus, the Siva–pyrin interaction may be a potential target for future therapeutic strategies. J. Cell. Physiol. 216: 595–602, 2008, © 2008 Wiley‐Liss, Inc.
Characterization of Ni(II) complexes of Schiff bases of amino acids and (S)‐N‐(2‐benzoylphenyl)‐1‐benzylpyrrolidine‐2‐carboxamide using ion trap and QqTOF electrospray ionization tandem mass spectrometry
Authors: Jirásko Robert , Holčapek Michal , Kolářová Lenka , Nádvorník Milan , Popkov Alexander
Published: March 2008

This work demonstrates the application of electrospray ionization mass spectrometry (ESI‐MS) using two different mass analyzers, ion trap and hybrid quadrupole time‐of‐flight (QqTOF) mass analyzer, for the structural characterization of Ni(II) complexes of Schiff bases of (S)‐N‐(2‐benzoylphenyl)‐1‐benzylpyrrolidine‐2‐carboxamide with different amino acids. ESI enables the determination of molecular weight on the basis of rather simple positive‐ion ESI mass spectra containing only protonated molecules and adducts with sodium or potassium ions. Fragmentation patterns are characterized by tandem mass spectrometric experiments, where both tandem mass analyzers provide complementary information. QqTOF data are used for the determination of elemental composition of individual ions due to mass accuracies always better than 3 ppm with the external calibration, while multistage tandem mass spectra obtained by the ion trap are suitable for studying the fragmentation paths. The novel aspect of our approach is the combination of mass accuracies and relative abundances of all isotopic peaks in isotopic clusters providing more powerful data for the structural characterization of organometallic compounds containing polyisotopic elements. The benefit of relative and absolute mean mass accuracies is demonstrated on the example of studied Ni(II) complexes. Copyright © 2008 John Wiley & Sons, Ltd.
Classification and geometric aspects of vector valued Fourier transforms
Authors: Park In Sook
Published: March 2008

It is shown that for any locally compact abelian group 𝔾 and 1 ≤ p ≤ 2, the Fourier type p norm with respect to 𝔾 of a bounded linear operator T between Banach spaces, denoted by ‖T |ℱ𝒯𝔾p‖, satisfies ‖T |ℱ𝒯𝔾p‖ ≤ ‖T |ℱ𝒯𝔸p‖, where 𝔸 is the direct product of ℤ2, ℤ3, ℤ4, … It is also shown that if 𝔾 is not of bounded order then Cnp ‖T |ℱ𝒯𝕋p‖ ≤ ‖T |ℱ𝒯𝔾p‖, where 𝕋 is the circle group, n is a onnegative integer and Cp = . From these inequalities, for any locally compact abelian group 𝔾 ‖T |ℱ𝒯𝔾2‖ ≤ ‖T |ℱ𝒯𝕋2‖, and moreover if 𝔾 is not of bounded order then ‖T |ℱ𝒯𝔾2‖ = ‖T |ℱ𝒯𝕋2‖. The Hilbertian property and B‐convexity are discussed in the framework of Fourier type p norms. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Complexity penalized least squares estimators: Analytical results
Authors: Wittich O. , Kempe A. , Winkler G. , Liebscher V.
Published: March 2008

A simple variational approach to the estimation of timeseries is studied in detail and mathematical rigor. The functional in question is a complexity penalized sum of squares. The results include existence and uniqueness of the statistical estimate, as well as continuous dependence and stability in dependence on parameters and data. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Some preconditioners for the CFIE equation of electromagnetism
Authors: Levadoux David P.
Published: March 2008

We present three weak parametrices of the operator of the combined field integral equation (CFIE). An interesting feature of these parametrices is that they are compatible with different discretization strategies and hence allow for the construction of efficient preconditioners dedicated to the CFIE. Their numerical analysis shows that a regularization process acting at the continuous level of the equation is also effective at the discrete level if the mesh size tends to zero. First numerical tests confirm this effect and preconditioning is observed indeed. Furthermore, we show that the underlying operator of CFIE satisfies a uniform discrete Inf–Sup condition that allows one to predict an original convergence result for the numerical solution of CFIE to the exact one. Copyright © 2008 John Wiley & Sons, Ltd.
Molecular thermodynamic model of the glass transition temperature: dependence on molecular weight
Authors: Kim Yong Woo , Park Jung Tae , Koh Joo Hwan , Min Byoung Ryul , Kim Jong Hak
Published: March 2008

A new molecular thermodynamic model to predict the dependency of the glass transition temperature (Tg) of polymer on its molecular weight was developed based on the configurational entropy model and the Flory–Huggins theory. In this model, the disorientation entropy of the polymer (Sdis) has been taken into account. Quantitative descriptions according to the proposed model are consistent with experimental Tg data of several polymers against the number of chain segment (r). At the same Tg.∞ (Tg of polymer at a infinite r value), the degree of polymer disorientation is strongly correlated with the slope of straight line at lower r regions in the Tg versus r plot, which is quantitatively identified by physical parameter (γdis) in this model. Copyright © 2008 John Wiley & Sons, Ltd.
Association between medication and risk of suicide, attempted suicide and death in nationwide cohort of suicidal patients with schizophrenia
Authors: Haukka Jari , Tiihonen Jari , Härkänen Tommi , Lönnqvist Jouko
Published: March 2008

Purpose

Mortality among schizophrenia patients is substantially higher than in the general population. The aim of this study was to investigate, in a nationwide cohort of suicidal schizophrenic individuals, how the risks of suicide, severe suicide attempts and death are associated with usage of antidepressant or antipsychotic treatment.

Methods

The study population included all individuals in Finland who were hospitalised with a diagnosis of attempted suicide between 1 January 1997 and 31 December 2003, who also had at least one hospitalisation due to schizophrenia diagnosis (ICD‐10 F20), and were at least 16 years old when the index hospitalisation began. Cox's proportional hazards modelling and Bayesian intensity estimation were used in the analysis.

Results

There were 1611 patients with a mean follow‐up time of 4.3 years. Current use of antipsychotics was associated with decreased mortality due to suicide (HR 0.52, 95% CI 0.34–0.81, p = 0.004), but no significant decrease in mortality was observed during current use of antidepressants (0.66, 0.41–1.08, p = 0.099), when compared to past use. In more detailed analysis when current users were compared to non‐users, olanzapine, and mixed use of antipsychotics, were associated with reduced all‐cause mortality, and mixed use also with reduced risk of suicide mortality. Current use of citalopram was associated with decreased all‐cause and suicide mortality.

Conclusions

In a population of suicidal schizophrenic individuals antipsychotic medication, treatment was associated with lower mortality from suicide and all‐causes. Antidepressive medication was associated with lower all‐cause mortality when used in combination with antipsychotics. Copyright © 2008 John Wiley & Sons, Ltd.
Structural and enzymatic characterization of HP0496, a YbgC thioesterase from Helicobacter pylori
Authors: Angelini Alessandro , Cendron Laura , Goncalves Susana , Zanotti Giuseppe , Terradot Laurent
Published: March 2008

YbgC proteins are bacterial acyl‐CoA thioesterases associated with the Tol‐Pal system. This system is important for cell envelope integrity and is part of the cell division machinery. In E. coli, YbgC associates with the cell membrane and is part of a protein network involved in lipid biogenesis. In the human pathogen Helicobacter pylori, a putative homologue of YbgC, named HP0496, was found to interact with the cytotoxin CagA by two different studies. We have determined its crystal structure and characterized its enzymatic activity. The structure of HP0496 shows that it is a member of the hot‐dog family of proteins, with a εγ tetrameric arrangement. Finally, enzymatic assays performed with the purified protein showed that HP0496 is an acyl‐CoA thioesterase that favors long‐chain substrates. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Response to András Szilágyi's Commentary
Authors: Zbilut Joseph P. , Giuliani Alessandro , Webber Charles L.
Published: March 2008

In a commentary to our article on protein domain size, András Szilágyi suggests our findings are a mathematical artifact. In examining his concerns, we believe they are possibly a result of misunderstandings, errors of fact, and philosophical approach. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Conformation‐activity relationships of cyclo‐constrained µ/δ opioid agonists derived from the N‐terminal tetrapeptide segment of dermorphin/deltorphin
Authors: Rodziewicz‐MotowidŁo Sylwia , Czaplewski Cezary , Łuczak Sylwia , Ciarkowski Jerzy
Published: March 2008

The N‐terminal tetrapeptide segments of dermorphin (Tyr–D‐Ala–Phe–Gly–Tyr–Pro–Ser–NH2) and deltorphin (Tyr–D‐Ala–Phe–Asp/Glu–Val–Val–Gly–NH2) are agonists at the opioid receptors µ and δ, respectively. [D‐Arg2, Lys4]‐dermorphin‐(1–4) amide (Tyr–D‐Arg–Phe–Lys–NH2, DALDA) and [Dmt1]DALDA (where Dmt is 2′,6′‐dimethyltyrosine) are among the most potent and selective µ‐agonists reported to date, both in vitro (having picomolar µ receptor affinity) and in vivo. In this communication, conformation‐activity studies of the following four cyclic analogs of DALDA are presented and discussed: the lead peptide S2,S4‐cyclo (Tyr–D‐Cys–Phe–Cys–NH2), constrained by means of an S4.2S4.4 disulfide between Cys2 and Cys4; its two cis and trans C4.2C4.4‐olefinic dicarba analogs, and the product of saturation of them both. They are potent nonselective or moderately µ‐selective opioid agonists in vitro.

They have been synthesized and tested earlier [Berezowska I, Chung NN, Lemieux C, Wilkes BC, and Schiller PW, Acta Biochim Polon 53, 2006, 73–76]. We have studied their conformations using NMR and molecular dynamics. With major conformational constraints imposed by the 11‐membered ring spanning residues 2–4, they show well defined conformations of this ring, while the exocylic Tyr1 and Phe3 side chains still have significant conformational freedom. The more active and selective µ versus δ disulfide and saturated dicarba agonists seem to have in common: (i) their ring structures more flexilble than those of the other two and (ii) their ring structures similar to each other and more diverse than those in the other two. Given this and the small size of the peptides having confirmed bioactivity profiles, there is a chance that their conformations determined in solution approach receptor‐bound conformations. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Surface modification of Ti by an Ar‐O mixture dc plasma
Authors: Valencia R. A. , de la Piedad‐Beneitez A. , de la Rosa‐Vázquez J. , López‐Callejas R. , Barocio S. R. , Mercado‐Cabrera A. , Peña‐Eguiluz R. , Muñoz‐Castro A. E.
Published: March 2008

Titanium surface oxidation deserves a growing interest in biomedical engineering due to its biocompatibility enhancement and mechanical performance. In this work we report on the Ti surface modification, conducted into a toroidal vacuum vessel, by a DC plasma formed by an oxygen‐argon (20/80) mixture. By varying the gas pressure within the 2.5 to 5×10–3 mbar interval at the sample bias voltage –3000 V, we have gained control over the sample temperature up to the order of 650°C. In turn, the composition of the modified surface has been controlled by adjusting the flow rates of the gas mixture and the above mentioned temperature. The samples were characterised by microhardness tests, SEM, XRD and Raman spectroscopy. The diagnostics revealed a rutile TiO2 and TiO1.04 phase content in the modified layer. The remarkable effects of Ti sample temperature and treatment time on the morphology of the surface structure were explored. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Monitoring of electric potential of semiconductor wafer
Authors: Noras Maciej A. , Maryniak William A.
Published: March 2008

The International Technology Roadmap for Semiconductors (ITRS) forecasts increasing number of issues with electrostatic discharge (ESD) related phenomena and the need for improved wafer electrostatic charge control in semiconductor wafer processing. This means that wafer metrology should encompass charge measurements as a routine operation. The ability to make wafer potential measurements in‐line, either before and after the wafer processing can help with detection and prevention of the ESD events and with minimizing wafer charging issues during loading/unloading operations. One of the instruments utilized in such measurements is an electrostatic voltmeter (ESVM). In this paper the authors would like to introduce and discuss novel designs of the ESVMs. A new, non‐contacting probe allows for the measurement of surface voltages with DC stability and millivolt sensitivity. Another design features a specially designed probe that permits contact with the wafer surface without transfer of the electric charge to/from the surface under test. Results of performance evaluation along with feasibility studies of the sensors are presented. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Deuterium retention near surface of TiO2 by low‐voltage D2 plasma discharge
Authors: Matsunami N. , Tanaka T. , Ohno N. , Tokitani M.
Published: March 2008

We have investigated deuterium (D) uptake in TiO2 (rutile) films under exposure of low‐energy D2+ ions and thermal release of D from TiO2 films. The amount of deuterium in the films was analysed by means of nuclear reaction analysis, D(3He, α)p. D‐uptake under AC‐glow discharge in D2 pressure of ∼90 Pa is compared with that under DC‐discharge with well‐defined energy of D2+ ions in D2 pressure of ∼0.1 Pa. The results imply that the effective energy of D2+ ions in AC‐glow discharge is much lower than the energy derived from the applied voltage. The results are also compared with those for Ti sheet exposed to low‐energy D2+ ions. We find that D‐release temperature from TiO2 is considerably lower than from Ti, though D‐uptake in TiO2 is smaller than in Ti. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Background‐error correlation length‐scale estimates and their sampling statistics
Authors: Pannekoucke O. , Berre L. , Desroziers G.
Published: March 2008

This article presents different formulae to estimate correlation length‐scales, and an evaluation of their qualities for practical diagnostic applications. In particular, two new and simple formulae are introduced, which only require the computation of correlation with a single point for a given direction. It is then shown in a 1D heterogeneous context that all formulations lead to similar realistic length‐scale values, and that they represent geographical variations rather well.

The estimation of length‐scales within a finite ensemble is also studied. While a positive bias occurs when the ensemble size is too small, the standard deviation of the length‐scale estimation is shown to be the main influence on the estimation error. The spatial structure of sampling noise is then diagnosed, and effects of spatial filtering techniques on the bias and standard deviation are illustrated.

Finally, an ensemble of perturbed forecasts from a global NWP model is used, showing a real application example. Copyright © 2008 Royal Meteorological Society
Maintenance contract assessment for aging systems
Authors: Lisnianski Anatoly , Frenkel Ilia , Khvatskin Lev , Ding Yi
Published: March 2008

This paper considers an aging system, where the system failure rate is known to be an increasing function. After any failure, maintenance is performed by an external repair team. Repair rate and cost of repair are determined by a corresponding maintenance contract with a repair team. There are many different maintenance contracts suggested by the service market to the system owner. In order to choose the best maintenance contract, a total expected cost during a specified time horizon should be evaluated for an aging system. In this paper, a method is suggested based on a piecewise constant approximation for the increasing failure rate function. Two different approximations are used. For both types of approximations, the general approach for building the Markov reward model is suggested in order to assess lower and upper bounds of the total expected cost. Failure and repair rates define the transition matrix of the corresponding Markov process. Operation cost, repair cost and penalty cost for system failures are taken into account by the corresponding reward matrix definition. A numerical example is presented in order to illustrate the approach. Copyright © 2008 John Wiley & Sons, Ltd.
Surface characterization of polyester resins formulated with different cross‐linking agents
Authors: Marino Paolo , Lowe Chris , Abel Marie‐Laure , Watts John F.
Published: March 2008

Three thermally cured coatings, formulated on a low Tg isophthalic‐based polyester, were investigated by XPS and ToF‐SIMS. A model formulation was employed for all three coatings investigated; however, the cross‐linking agents used were varied for each formulation. Hexamethoxymethyl melamine (HMMM), tris‐isocyanurate (TIC), and a combination of HMMM and TIC were included as the cross‐linking agents. The use of TIC alone required a tin‐based catalyst to promote the curing reaction.

The aim of this work was to investigate the difference in the surface compositions of the three coatings and the distribution of the different cross‐linking agents used. This was in preparation for further studies which will involve interfacial analysis in order to elucidate the mechanism responsible for intercoat adhesion.

The XPS analysis of the coating surfaces revealed a nitrogen concentration consistent with the concentration expected from the formulation for the coating containing HMMM. In the other two formulations a lower concentration than calculated was observed. The surface concentration of the two cross‐linking agents was not influenced by the presence of the others; indeed, the formulation containing both cross‐linking agents was, in terms of nitrogen concentration, merely a simple combination of the other two coatings. Peaks diagnostic of the cross‐linking agents were observed in ToF‐SIMS spectra acquired from the coating surfaces. By using XPS and ToF‐SIMS analysis, we could determine that the HMMM and the TIC have a different distribution at the coating surface, that is not affected by the presence of the other. Copyright © 2008 John Wiley & Sons, Ltd.
Insight into the Enzymatic Degumming Process of Soybean Oil
Authors: Yang Bo , Zhou Rong , Yang Ji‐Guo , Wang Yong‐Hua , Wang Wei‐Fei
Published: March 2008

An enzymatic degumming trial of soybean oil was carried out at a capacity of 400 tons/day by applying microbial phospholipase A1 from Thermomyces lanuginosus/Fusarium oxysporum. When the pH was kept in the range of 4.8–5.1, less than 10 mg/kg of phosphorous content of The oil was obtained. The gum and oil were easily separated after centrifugation and the oil loss was minimal under the process conditions. Through analysis of phospholipids compounds in the gum by Electrospray Ionization‐Mass Spectrometer and phosphorous content, it could be seen that both glycerophospholipids and lysophospholipids existed with contents of 45.7 and 54.3%, respectively. The performance of enzymatic degumming was found to be related to the production of glycerophospholipids.
Synthesis of Ethyl 5Z,9Z,12Z‐octadecatrienoate (ethyl pinolenate) and Methyl 12Z,15Z‐octadecadienoate
Authors: Kaltia Seppo , Matikainen Jorma , Ala‐Peijari Maija , Hase Tapio
Published: March 2008

Pinolenic acid (5Z,9Z,12Z‐octadecatrienoic acid, 1a), one of the most abundant trienoic fatty acids in nature, is very difficult to obtain in quantity in a pure state from the highly complex mixture of unsaturated tall oil fatty acids. For this reason its chemistry has been little studied when compared to linolenic or linoleic acids. A simple synthesis of esters of 1a and of 12Z,15Z‐octadecadienoic acid 3 using the one pot double Wittig procedure is described here. The products of double Wittig reactions were purified by argentation chromatography, and their structural purity was established by 1H‐, 13C‐NMR and 2D‐NMR spectroscopies.
Source of modality: a reassessment
Authors: DEPRAETERE ILSE , VERHULST AN
Published: March 2008

This article offers a description of the sources associated with the necessities expressed byhave toandmustin the ICE-GB corpus. It provides detailed comments on semantic and pragmatic features of the different sources, which are shown to be more diverse than has previously been claimed. The corpus analysis proves that the traditional distinction in meaning between so-called ‘objective’have toand ‘subjective’mustis not as outspoken as is assumed, and therefore results in a more accurate description of the similarities and differences in meaning between the two modal markers.
RIGHTS AND SLAVERY, RACE AND RACISM: LEO STRAUSS, THE STRAUSSIANS, AND THE AMERICAN DILEMMA
Authors: KING RICHARD H.
Published: March 2008

My interest here is in the way Leo Strauss (1899–1973) and his followers, the Straussians, have dealt with race and rights, race and slavery in the history of the United States. I want, first, to assess Leo Strauss's rather ambivalent attitude toward America and explore the various ways that his followers have in turn analyzed the Lockean underpinnings of the American “regime,” sometimes in contradistinction to Strauss's views on the topic. With that established, I turn to the account, particularly that offered by Harry Jaffa, of how slavery and race comported—or did not—with the Straussian account of the political foundations of the new nation and how latter-day followers of Strauss have dealt with the persisting topic of race and racism in America. Overall, I want to make two large points. First, the Straussian commitment to superhistorical standards provides the Straussians with a moral perspective on slavery, race, and racism. Second, though race and slavery have been less than central among the concerns of most followers of Strauss, the contributions of Jaffa and others have significantly shaped the present American conservative position on race, including the idea of color-blindness.
Rifampin and digoxin induction of MDR1 expression and function in human intestinal (T84) epithelial cells
Authors: Haslam I S , Jones K , Coleman T , Simmons N L
Published: March 2008

Background and purpose: Oral drug bioavailability is limited by intestinal expression of P‐glycoprotein (MDR1, Pgp, ABCB1) whose capacity is regulated via nuclear receptors e.g. the pregnane X receptor (PXR, SXR, NR1I2). In order to study dynamic regulation of MDR1 transport capacity we have identified the T84 epithelial cell‐line as a model for human intestine co‐expressing MDR1 with PXR. The ability of rifampin, a known PXR agonist and digoxin, a model MDR1 substrate, to regulate MDR1 expression and transport activity has been tested, in these T84 cells.

Experimental approach: Transport was assayed by bi‐directional [3H]‐digoxin transepithelial fluxes across epithelial layers of T84 cells seeded onto permeable filter supports following pre‐exposure to rifampin and digoxin. Quantitative real‐time PCR, Western blotting and immunocytochemistry were used to correlate induction of MDR1 transcript and protein levels with transport activity.

Key results: Rifampin exposure (10 μM, 72 hours) increased MDR1 transcript levels (3.4 fold), MDR1 total protein levels (4.4 fold), apical MDR1 protein (2.7 fold) and functional activity of MDR1 (1.2 fold). Pre‐incubation with digoxin (1 μM, 72 hours) potently induced MDR1 transcript levels (92 fold), total protein (7 fold), apical MDR1 protein (4.7 fold) and functional activity (1.75 fold). Whereas PXR expression was increased by rifampin incubation (2 fold), digoxin reduced PXR expression (0.3 fold).

Conclusions and implications: Chronic digoxin pre‐treatment markedly upregulates MDR1 expression and secretory capacity of T84 epithelia. Digoxin‐induced changes in MDR1 levels are distinct from PXR‐mediated changes resulting from rifampin exposure.
Social Responsibility and Innovation on Trafficking and Child Sex Tourism: Morphing of Practice into Sustainable Tourism Policies?
Authors: Tepelus Camelia M.
Published: March 2008

Ethical questions related to globalisation, human rights, unfair labour practices and trans-boundary exchanges of capital and workforce create ever more complex challenges for the tourism sustainability agenda. In recent years, the tourism industry has been increasingly challenged by media and governments to provide fast, socially responsible responses to emerging problems resulting from the dissolution of borders and workforce migration. Two particularly challenging phenomena that regularly make headlines are trafficking in human beings and child sex tourism. The main objective of this paper is to present existing good practices for preventing and combating trafficking of human beings and its links with the travel industry, and child sex tourism. Secondly, the paper calls for the morphing of empirical models into sustained innovation and public policies, and reviews several factors that may be necessary for this transformation to begin. The discussion is framed within the context of corporate social responsibility for sustainable tourism.
Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity
Authors: Suzuki Takayuki , Hasso Sean M. , Fallon John F.
Published: March 2008

The zone of polarizing activity is the primary signaling center controlling anterior–posterior patterning of the amniote limb bud. The autopodial interdigits (IDs) are secondary signaling centers proposed to determine digit identity by acting on the cells of the digital ray. Here, we focus on events accompanying digital fate determination and define a region of the digital ray that expresses
Sox9
and
Bmpr1b
and is phosphorylated-SMAD1/5/8 (
p
-SMAD1/5/8) positive. We name this region the phalanx-forming region (PFR), and show that the PFR cells arise from the distal subridge mesenchyme of digital ray. This phalanx-forming cell lineage is subsequently committed to the cartilage lineage; the fate of these cells is initially labile but becomes fixed as they are incorporated into the condensed cartilage of the digit primordium. Using an
in vivo
reporter assay, we establish that each digital PFR has a unique
p
-SMAD1/5/8 activity signature. In addition, we show that changes in this activity correlate with the identity of the digit that forms after experimental manipulation, supporting the idea that threshold signaling levels can lead to different developmental outcomes in a morphogenetic field. Our data define the molecular profile of the PFR, and we propose a model for understanding formation and variation of digits during autopodial development.
Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation
Authors: Sun Jianjun , Lang Alexander E. , Aktories Klaus , Collier R. John
Published: March 2008

The protective antigen (PA) moiety of anthrax toxin forms a heptameric pore in endosomal membranes of mammalian cells and translocates the enzymatic moieties of the toxin to the cytosol of these cells. Phenylalanine-427 (F427), a solvent-exposed residue in the lumen of the pore, was identified earlier as being crucial for the transport function of PA. The seven F427 residues were shown in electrophysiological studies to form a clamp that catalyzes protein translocation through the pore. Here, we demonstrate by a variety of tests that certain F427 mutations also profoundly inhibit the conformational transition of the heptameric PA prepore to the pore and thereby block pore formation in membranes. Lysine, arginine, aspartic acid, or glycine at position 427 strongly inhibited this acidic pH-induced conformational transition, whereas histidine, serine, and threonine had virtually no effect on this step, but inhibited translocation instead. Thus, it is possible to inhibit pore formation or translocation selectively, depending on the choice of the side chain at position 427; and the net inhibition of the PA transport function by any given F427 mutation is the product of its effects on both steps. Mutations inhibiting either or both steps elicited a strong dominant-negative phenotype. These findings demonstrate the dual functions of F427 and underline its central role in transporting the enzymatic moieties of anthrax toxin across membranes.