bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain volume changes in the first year of illness and 5-year outcome of schizophrenia
Authors: Cahn W. , van Haren N. E. M. , Pol H. E. Hulshoff , Schnack H. G. , Caspers E. , Laponder D. A. J. , Kahn R. S.
Published: November 2006

Progressive brain volume changes have been reported in first-episode schizophrenia, but their relationship to the disease process or to other factors remains unclear. We examined such changes in the first year of illness, and related them to 5-year outcome. Progressive brain volume changes, in particular of grey matter, during the first year of illness were found to be significantly associated with clinical and functional outcome 5 years after the first episode. These findings suggest that early dynamic brain volume changes are related to the disease process and predict the longer-term outcome of schizophrenia.
Episodic psychiatric disorders in teenagers with learning disabilities with and without autism
Authors: Bradley Elspeth , Bolton Patrick
Published: November 2006

Background

Mental health problems in people with learning disabilities and autism are poorly understood.

Aims

To investigate the prevalence of episodic psychiatric disorders in a sample of teenagers with learning disabilities with and without autism.

Method

Teenagers with learning disabilities living in one geographical area were identified. Those with autism were matched to those without. A semi– structured investigator-based interview linked to Research Diagnostic Criteria was used to assess prevalence and type of episodic disorders.

Results

Significantly more individuals with autism had a lifetime episodic disorder, most commonly major depression. Two individuals with autism had bipolar affective disorder. Other episodic disorders with mood components and behaviour change were also evident, as were un classifiable disorders characterised by complex psychiatric symptoms, chronicity and general deterioration. Antipsychotics and stimulants were most frequently prescribed; the former associated with episodic disorder, the latter with autism.

Conclusions

Teenagers with learning disabilities and autism have higher rates of episodic psychiatric disorders than those with learning disabilities alone.
Contribution of depression and anxiety to impaired health-related quality of life following first myocardial infarction
Authors: Dickens Chris M. , McGowan Linda , Percival Carol , Tomenson Barbara , Cotter Lawrence , Heagerty Anthony , Creed Francis H.
Published: November 2006

Background

The extent to which depression impairs health-related quality of life (HRQoL) in the physically ill has not been clearly established.

Aims

To quantify the adverse influence of depression and anxiety assessed at the time of first myocardial infarction and 6 months later, on the physical aspect of HRQoL 12 months after the infarction.

Method

In all, 260 in-patients, admitted following first myocardial infarction, completed the Hospital Anxiety and Depression Scale and the Medical Outcomes Study SF–36 assessment before discharge and at 6- and 12-month follow-up.

Results

Depression and anxiety 6 months after myocardial infarction predicted subsequent impairment in the physical aspects of HRQoL (attributable adjusted R2=9%, P<0.0005). These negative effects of depression and anxiety on outcome were mediated by feelings of fatigue. Depression and anxiety present before myocardial infarction did not predict HRQoL 12 months after myocardial infarction.

Conclusions

Detection and treatment of depression and anxiety following myocardial infarction improve the patient's health-related quality of life.
Circulating Nucleic Acids in Plasma/Serum and Tumor Progression
Authors: SAMOS JULIA , GARCÍA‐OLMO DOLORES C. , PICAZO MARÍA G. , RUBIO‐VITALLER ANTONIO , GARCÍA‐OLMO DAMIÁN
Published: November 2006

Abstract:  The “genometastasis hypothesis” proposes that cell‐free tumor nucleic acids might be able to transform host stem cells, and that this might be a pathway for the development of metastases. This theory is supported by previous experimental findings and is consistent with observations of other authors. It has been suggested that tumor DNA might be horizontally transferred by the uptake of apoptotic bodies and initiate the genetic changes that are necessary for tumor formation. In addition, apoptotic bodies have been proposed as possible vehicles that protect the nucleic acids circulating in the plasma from enzymatic degradation. In the present study, we analyzed the presence of apoptotic bodies in serum and its relationship with tumor progression in a heterotopic model of colon cancer in the rat. We injected DHD/K12‐PROb cancer cells subcutaneously into BD‐IX rats and divided the animals into three groups according to the time between the injection of tumor cells and euthanasia. A control group of healthy animals was included (n= 6). After euthanasia, macroscopic metastases were assessed and samples of blood were collected. To detect apoptotic bodies in the sera, each sample was mixed with FITC‐conjugated annexin V antibody in combination with propidium iodide and then analyzed by flow cytometry. Detection of apoptotic bodies was only significantly increased in the sera of a few tumor‐bearing animals in late stages of tumor development. Thus, such particles appear not to be the vehicle of the cell‐free tumor nucleic acids that are detected at early stages of cancer.
Early and Specific Prediction of the Therapeutic Efficacy in Non–Small Cell Lung Cancer Patients by Nucleosomal DNA and Cytokeratin‐19 Fragments
Authors: HOLDENRIEDER STEFAN , STIEBER PETRA , VON PAWEL JOACHIM , RAITH HANNELORE , NAGEL DOROTHEA , FELDMANN KNUT , SEIDEL DIETRICH
Published: November 2006

Abstract:  Facing an era of promising new antitumor therapies, predictors of therapy response are needed for the individual management of treatment. In sera collected prospectively from 311 patients with advanced non‐small cell lung cancer receiving first‐line chemotherapy, changes in nucleosomal DNA fragments, cytokeratin‐19 fragments (CYFRA 21–1), carcinoembryonic antigen (CEA), neuron‐specific enolase (NSE), and progastrin‐releasing peptide (ProGRP) were investigated and correlated with therapy response. In univariate analysis, high levels, slower and incomplete decline in nucleosomal DNA, CYFRA 21–1, and CEA predicted poor outcome. DNA concentrations at day 8 of the first therapeutic cycle and CYFRA 21–1 before start of the second cycle were identified as best predictive variables. In multivariate analysis, they predicted progression with a specificity of 100% in 29% of the cases earlier than imaging techniques. Thus, nucleosomal DNA and CYFRA 21–1 specifically identify a subgroup of patients with insufficient therapy response at the early treatment phase and showed to be valuable for disease management.
Novel binding partners of Ldb1 are required for haematopoietic development
Authors: Meier Natalia , Krpic Sanja , Rodriguez Patrick , Strouboulis John , Monti Maria , Krijgsveld Jeroen , Gering Martin , Patient Roger , Hostert Arnd , Grosveld Frank
Published: November 2006

Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in a number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form a transcription factor complex regulating late erythroid genes. We identify a number of novel Ldb1 interacting proteins in erythroleukaemic cells, in particular the repressor protein Eto-2 (and its family member Mtgr1), the cyclin-dependent kinase Cdk9, and the bridging factor Lmo4. MO-mediated knockdowns in zebrafish show these factors to be essential for definitive haematopoiesis. In accordance with the zebrafish results these factors are coexpressed in prehaematopoietic cells of the early mouse embryo,although we originally identified the complex in late erythroid cells. Based on the change in subcellullar localisation of Eto-2 we postulate that it plays a central role in the transition from the migration and expansion phase of the prehaematopoietic cells to the establishment of definitive haematopoietic stem cells.
Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina
Authors: Feng Liang , Xie Xiaoling , Joshi Pushkar S. , Yang Zhiyong , Shibasaki Koji , Chow Robert L. , Gan Lin
Published: November 2006

The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes.
Theoretical Studies on the Structure and Dynamics of Water, Ice, and Clathrate Hydrate
Authors: Tanaka Hideki , Koga Kenichiro
Published: November 2006

We have investigated various anomalous properties of water such as the divergent character of the thermodynamic functions and liquid–liquid transition in supercooled water, the phase behaviors of water and new ices in nanoscale confinement, the thermodynamic stability of clathrate hydrates over a wide range of pressure, and anomalous thermodynamic and structural properties of ices. These are studied by some theoretical calculations and Monte Carlo/molecular dynamics computer simulations. It is demonstrated that the potential energy surface and the connectivity of supercooled water are keys to understand why liquid–liquid transition can take place in deeply supercooled water. A tetrahedral coordination of water is preserved even in extreme confinements, forming tubule ice and bilayer crystalline (or amorphous) ice, although the heavy stress makes the bond angles and lengths different from the ideal values. Thermodynamic stability of clathrate hydrates, including double occupancy, is more accurately predicted by considering the host–guest coupling and other factors. The negative thermal expansivity and the change in slope of the Debye–Waller factor of ice are explained with a simple model of water.
One-Pot Synthesis of Soluble Precursors Possessing Both Al–N and B–N Backbones and Their Pyrolysis
Authors: Mori Yusuke , Sugahara Yoshiyuki
Published: November 2006

Soluble precursors possessing both Al–N and B–N backbones have been prepared from LiAlH4, LiBH4, and RNH2·HCl (R = Me and Et) in one pot. The infrared (IR) and nuclear magnetic resonance (NMR) spectra of the precursors indicate that the precursors possess Al–H and B–H groups as well as Al–N, B–N, Al–(μ-H)2–Al, and Al–(μ-H)2–B bonds. TG analysis reveals that the ceramic yield of the precursor [AB11_Me (LiAlH4/LiBH4/MeNH2·HCl = 1/1/2)] up to 1000 °C under an argon atmosphere is 74.4 mass %. The transmission electron microscopic (TEM) images and the X-ray diffraction (XRD) pattern of AB11_Me that was pyrolyzed at 1600 °C indicate that the average size of crystalline aluminum nitride (AlN) is about 14 nm and that crystalline AlN particles are distributed homogeneously in an amorphous matrix.
A Simple Preconcentration-Storing Technique Based on Sulfide Precipitation for Multipoint Monitoring of Mercury in Rainwater and Snow by Cold Vapor Atomic Absorption Spectrometry
Authors: Kagaya Shigehiro , Serikawa Yuka , Yashima Ryosuke , Tanaka Toshiyuki , Hasegawa Kiyoshi
Published: November 2006

A preconcentration-storing technique that does not require any special or expensive apparatus and reagents was developed to monitor mercury in rainwater and snow at many points as simultaneously as possible. A commercially available sodium hypochlorite solution was added to the sample solution to prevent a decrease in mercury concentration after sampling. Mercury(II) ion (0.5–50 ng) in 500 mL of the sample solution was concentrated by adding zinc(II) ion and a small amount of sulfide ion and then coagulating/coprecipitating with Zn(OH)2 or ZnS after reduction of residual hypochlorite by addition of hydroxylammonium chloride. The supernatant solution was discarded by decantation, and the solution including the precipitates could be stored for at least 20 days without any loss of mercury. The recoveries of mercury(II) ion from the 500 mL of the sample solutions spiked with mercury(II) ions were 99–109%, with standard deviation ranges of 3–8%, although the recovery of methylmercury(II) ion was 68 ± 5%. Using this technique, the determination of mercury in rainwater and snow was demonstrated at Toyama Prefecture, Japan, from April 2004 to February 2005; mercury levels ranging from 2.7 to 33.7 ng L−1 were found.
Development of a New Type of Open Tubular Capillary Liquid Chromatography System Based on Microphase Separation of Mixed Solvents
Authors: Tabata Masaaki , Wu Ying Guang , Charoenraks Thiraporn , Samaratunga Sethsiri Sunil
Published: November 2006

This paper describes a new type of open tubular capillary liquid chromatography (OTCLC) which utilizes the microheterogenities and preferential solvation phenomena in organic-water mixed solvents. Several model compounds have been separated by the proposed OTCLC system, and it has been confirmed the separation occurs due to the micro-phase separation of the mobile phase enhanced by salts. The well-known Golay equations were applied to characterize and optimize the OTCLC system.
Geometrical Analysis to Understand the Ability of Halogen Atoms to Act as Hydrogen-Bond Acceptors: A Structural Database Study
Authors: Malathy Sony Subramanian Manimekalai , Ponnuswamy Mondikalipudur Nanjappa
Published: November 2006

Non-covalent interactions involving halogen atoms play a major role in supramolecular chemistry, biochemistry, coordination and organometallic chemistry and also act as conformation-determining factors. Therefore, the hydrogen-bonding nature of the halogen acceptors in solid state are analyzed statistically, and the geometrical characteristics of weak hydrogen-bonded interactions are studied for the oxygen, nitrogen, and carbon atom donors. The hybridization states of the donor atoms and the different coordination environment of the halogen acceptors were also considered. The distance and the directionality characteristics that dictate the hydrogen bonds are given importance. Oxygen and nitrogen donors both showed the ability to form a strong hydrogen bond whereas carbon donors formed weak hydrogen bonds. The hydrogen-bonding nature of the carbon donor with a halogen acceptor was proven with this analysis; however, it had a hydrogen···acceptor distance cutoff of 2.7 Å for chlorine. Different hybridization states of the donor atoms did not significantly change the nature of the interaction; however, various coordination environments had some effect.
Reversible Photodissociation of Hexacarbonyl Tungsten in Cross-Linked Polymers
Authors: Watanabe Akira , Watanabe Tomoko , Shan Yue Jin , Tezuka Keitaro , Imoto Hideo , Uedono Akira
Published: November 2006

Reversible photochromic reaction of hexacarbonyltungsten(0) caused by the photodissociation of a carbonyl ligand was studied in cross-linked transparent polymers: polymer of bis(hydroxymethyl)tricyclo[5,2,1,02,6]decane dimethacrylate (A) and polymer of tetrakis(hydroxymethyl)methane tetrakis(acrylate) (B). Rate constants of the photodissociation and recombination reactions were determined from the observed spectral changes. Because the dimensions of the cavities in these polymers, determined by the positron annihilation experiments, were similar to those of the complex [W(CO)6], the photoactivated complexes could contribute to the coloring of the polymer only when the dissociated CO molecule moved to the neighboring space. In polymer B, with a higher density of cross-links between polymer chains, the complex had a higher dissociation rate constant but a lower saturation concentration. These results indicated that the kinetics of the dissociation are controlled by thermal motion of the polymer chains around the gate to the neighboring space. The decay of the complex after recycling of the dissociation–recombination process was much smaller in polymers, especially in polymer B, than in DMF solution.
Utilization of an Aromatic [4.4.4]Propellane as Thermally Stable Hole-Transport Materials in OLEDs
Authors: Kimura Makoto , Kuwano Seiichi , Shimada Kou , Kamata Ryouko , Yasuda Shuji , Sawaki Yasuhiko , Fujikawa Hisayoshi , Noda Koji , Taga Yasunori , Takagi Katsuhiko
Published: November 2006

In order to develop the thermally stable hole-transport materials (HTMs) in organic light-emitting diodes (OLEDs), hexabenzo-annulated [4.4.4]propellane that has three-biphenyl substructures around the C–C hub has been exploited as the core substance. Introduction of bis-, tetrakis-, or hexakis(diphenylamino) substituents at the 4 and 4′-positions of each biphenyl moiety leads to monomeric, dimeric, and trimeric derivatives of N,N,N′,N′-tetraphenylbenzidine; N,N′-bis(3-methylphenyl)-N,N′-diphenylbenzidine (TPD) has excellent electroluminescent (EL) characteristics but low thermal stability. The key step in the preparation of these derivatives (2S-, 4S-, and 6S-P) was the coupling of appropriate fluorenes with requisite ortho-bromo biphenyl compounds. All of these had not only excellent EL characteristics, but also glass transition temperatures (Tg) of over 120 °C which was higher than that of TPD (62 °C) representative of the HTM. This result is consistent with that the parent hydrocarbon is unusually stable even at 300 °C. Structural effects of the present monomeric to trimeric TPD analogues on the thermal stability and EL characteristics are discussed.
Elastic Analysis of Straight Members at Elevated Temperatures
Authors: Bradford Mark A.
Published: November 2006

The inherent expense of conducting full-scale experiments on steel members at elevated temperatures reinforces the need for accurate and reliable theoretical modelling, in order to assess their structural response under fire loading. The behaviour of steel members at elevated temperatures is quite complex and often counter-intuitive, and hitherto advanced finite element packages have been preferred over more generic or analytical solutions. Because of this, the significance of some parameters that influence the behaviour greatly may be lost. This article presents a generic modelling of the behaviour of a restrained beam member in a compartment fire, using the philosophy of a sub-assembly approach in lieu of a global modelling of the structure, which is allowed by the Eurocode standard. The analysis is elastic and therefore ignores yielding and the catenary effects that result at higher temperatures, and is based on the theorems of virtual work which allows for the prescription of governing differential equations of equilibrium and of the static boundary conditions. The equations of equilibrium are solved for some specific cases of restraint, and it is shown how the analytical solutions lead directly to prescriptive modelling of the structural behaviour, and importantly these equations lend themselves readily to codification in fire engineering design.
Exact and Semi-Analytical Finite Strip for Vibration and Dynamic Stability of Traveling Plates with Intermediate Supports
Authors: Hatami S. , Azhari M. , Saadatpour M. M.
Published: November 2006

Sing the exact finite strip method, a precise solution for linear free vibration and stability of an axially moving plate subjected to plane stresses is obtained. The plate may travel over multiple line supports. Exact natural frequencies and the speed at the onset of instability in the travelling plate can be identified for different boundary conditions and plate dimensions. In addition, a semi-analytical finite strip formulation has been developed for traveling plates with arbitrary boundary conditions and various in-plane loads. Modelling with a system of elastic springs, allows interior point and line supports for the plates to be taken into account. For moving plates, the effect of dimensional ratio in-plane loads and boundary conditions on free vibration, and stability characteristics of the plates were investigated and are described in this article. The influence of speed of plate motion and interior supports on the vibration frequency of the moving plates has also been studied and is illustrated with examples.
Deficient Bridge Mobility Performance Measures
Authors: Farhey Daniel N.
Published: November 2006

The structural and functional performances of bridges affect their safety, mobility, and life span. The concepts of structural deficiency and functional obsolescence of bridges are essential engineering and management considerations with public and economic implications. This article discusses management aspects of deficient bridges. National bridge inventory database with conditional data and mobility measures were studied to compile practical data for more dependable decision-making. A forecast was developed to predict the number of structurally deficient and functionally obsolete bridges in the future. To reach a systematic conceptualization of deficiency, areas of bridges were also discussed as compared to the count of bridges. The resulting study is practical for transportation agencies, officials, and researchers. The presented result supports better bridge management practices by better planned policies, financial resources, and strategies.
Ultimate Strength Interaction of Bending and Torsion of Steel/Concrete Composite Trapezoidal Box Girders in Positive Bending
Authors: Kim Kyungsik , Yoo Chai H.
Published: November 2006

In the case of horizontally curved highway bridges, girders are subjected to the combined action of vertical bending and torsion due to the offset. Although steel/concrete composite sections are proportioned to avoid abrupt brittle failure, the ultimate strengths of composite box girders subjected to bending and torsion may be limited by the diagonal tensile stress in the deck concrete induced by the St. Venant torsion. Concurrent compressive stresses in the concrete deck improve the shear resisting capacity of concrete, thereby resulting in increased torsional resistance of the composite box girder in positive bending. Three-dimensional finite element analyses and classical strength of materials investigations were conducted in this study to determine the ultimate strengths of composite box girders in bending and torsion and their interaction. An advanced material model including the concrete tension mechanism was incorporated in the incremental nonlinear analyses. The ultimate strengths from numerical data were compared with theoretically derived values. The proposed interaction equation is very simple, yet it provides a rational lower bound for the determination of the ultimate strengths of concrete/steel composite box girders.
Seismic Ductility Reduction Factors for Multi-Degree-of-Freedom Systems
Authors: Cai Jian , Zhou Jing , Fang Xiaodan
Published: November 2006

This paper reports on investigations into seismic ductility reduction factors for MDOF systems. Ductility reduction factors for MDOF systems are obtained by modifying ductility reduction factors of SDOF systems through a modification factor. Based on China's seismic code, MDOF lumped-mass shear-type models are introduced and employed to study the modification factors that can be used to calculate the lateral strength demand of MDOF systems. The four main parameters of site characteristics, number of storeys, displacement ductility ratio and fundamental period of the system, have been investigated to gain insight into the modification factors. It is demonstrated that ductility reduction factors for MDOF systems are clearly smaller than those for SDOF systems. The modification factor is mainly affected by the number of storeys, and the fundamental period. The ductility ratio also has an important influence on the modification factor and can't be neglected. Analysis results also indicate that the coefficient of variation for the modification factor increases with increasing number of storeys, fundamental period and ductility ratio. Finally, based on the results of a comprehensive statistical study on modification factors a simplified expression is suggested, which can conservatively estimate the modification factor required.
The frequency of translational misreading errors in E. coli is largely determined by tRNA competition
Authors: Kramer Emily B. , Farabaugh Philip J.
Published: November 2006

Estimates of missense error rates (misreading) during protein synthesis vary from 10−3 to 10−4 per codon. The experiments reporting these rates have measured several distinct errors using several methods and reporter systems. Variation in reported rates may reflect real differences in rates among the errors tested or in sensitivity of the reporter systems. To develop a more accurate understanding of the range of error rates, we developed a system to quantify the frequency of every possible misreading error at a defined codon in Escherichia coli. This system uses an essential lysine in the active site of firefly luciferase. Mutations in Lys529 result in up to a 1600-fold reduction in activity, but the phenotype varies with amino acid. We hypothesized that residual activity of some of the mutant genes might result from misreading of the mutant codons by tRNALysUUUU, the cognate tRNA for the lysine codons, AAA and AAG. Our data validate this hypothesis and reveal details about relative missense error rates of near-cognate codons. The error rates in E. coli do, in fact, vary widely. One source of variation is the effect of competition by cognate tRNAs for the mutant codons; higher error frequencies result from lower competition from low-abundance tRNAs. We also used the system to study the effect of ribosomal protein mutations known to affect error rates and the effect of error-inducing antibiotics, finding that they affect misreading on only a subset of near-cognate codons and that their effect may be less general than previously thought.
Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment
Authors: Merz Christian , Urlaub Henning , Will Cindy L. , Lührmann Reinhard
Published: November 2006

The deposition of proteins onto newly spliced mRNAs has far reaching consequences for their subsequent metabolism. We affinity-purified spliced human mRNPs under physiological conditions from HeLa nuclear extract and present the first comprehensive inventory of their protein composition as determined by mass spectrometry. Several proteins previously not known to be mRNP-associated were detected, including the DEAD-box helicases DDX3, DDX5, and DDX9, and the ELG, hNHN1, BCLAF1, and TRAP150 proteins. The association of some of the newly identified mRNP proteins was shown to be splicing-dependent, but not to require EJC formation. Initial recruitment of EJC proteins to the spliceosome did not require an EJC binding platform at the −20/24 region of the 5′ exon. Finally, while recruitment of EJC proteins and stable EJC formation were not dependent on the cap binding complex, several of the newly identified mRNP proteins required the latter for their association with mRNPs. These results provide novel insights into the composition of spliced mRNPs and the requirements for the association of mRNP proteins with the newly spliced mRNA.
The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect
Authors: Benedetti Fabrizio , Amanzio Martina , Vighetti Sergio , Asteggiano Giovanni
Published: November 2006

Despite the increasing research on placebos in recent times, little is known about the nocebo effect, a phenomenon that is opposite to the placebo effect and whereby expectations of symptom worsening play a crucial role. By studying experimental ischemic arm pain in healthy volunteers and by using a neuropharmacological approach, we found that verbally induced nocebo hyperalgesia was associated to hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, as assessed by means of adrenocorticotropic hormone and cortisol plasma concentrations. Both nocebo hyperalgesia and HPA hyperactivity were antagonized by the benzodiazepine diazepam, suggesting that anxiety played a major role in these effects. The administration of the mixed cholecystokinin (CCK) type-A/B receptor antagonist proglumide blocked nocebo hyperalgesia completely but had no effect on HPA hyperactivity, which suggests a specific involvement of CCK in the hyperalgesic but not in the anxiety component of the nocebo effect. Importantly, both diazepam and proglumide did not show analgesic properties on basal pain, because they acted only on the nocebo-induced pain increase. These data indicate a close relationship between anxiety and nocebo hyperalgesia, in which the CCKergic systems play a key role in anxiety-induced hyperalgesia. These results, together with previous findings showing that placebo analgesia is mediated by endogenous opioids, suggest that the analgesic placebo/hyperalgesic nocebo phenomenon may involve the opposite activation of endogenous opioidergic and CCKergic systems.
High Sensitivity to Neuromodulator-Activated Signaling Pathways at Physiological [K+] of Confocally Imaged Respiratory Center Neurons in On-Line-Calibrated Newborn Rat Brainstem Slices
Authors: Ruangkittisakul Araya , Schwarzacher Stephan W. , Secchia Lucia , Poon Betty Y. , Ma Yonglie , Funk Gregory D. , Ballanyi Klaus
Published: November 2006

The pre-Bötzinger complex (PBC) inspiratory center remains active in a transverse brainstem slice. Such slices are studied at high (8–10 mm) superfusate [K+], which could attenuate the sensitivity of the PBC to neuromodulators such as opiates. Findings may also be confounded because slice boundaries, drug injection sites, or location of rhythmogenic interneurons are rarely verified histologically. Thus, we first generated PBC slices with defined boundaries using novel “on-line histology” based on our finding that rostrocaudal extensions of brainstem respiratory marker nuclei are constant in newborn rats between postnatal days 0–4. At physiological superfusate [K+] (3 mm), 500- and 600-μm-thick slices with the PBC in the center and the caudal boundary 0.70 and 0.76 mm caudal to the facial motonucleus generated rhythm for >2 and ∼4 h, respectively. Rhythm was abolished by low nanomolar concentrations of the μ-opiate receptor agonist DAMGO ([d-Ala2,N-Me-Phe4, Gly5-ol]enkephalin). After spontaneous arrest of bursting, rhythm was reactivated at clinically relevant or physiological concentrations by 3,5-dihydroxyphenylglycine, thyrotropin-releasing hormone, or rolipram, each affecting distinct second-messenger pathways. Two-photon/confocal Ca2+imaging revealed that these agents reactivated the same PBC neurons initially active in 3 mm[K+]. The data show that “calibrated” PBC slices at physiological [K+] generate rhythm with a high sensitivity to neuromodulators for extended time periods, whereas spontaneous “in vitroapnea” is an important tool to study the interaction of signaling pathways that modulate rhythm. Our approaches and findings provide the basis for a pharmacological and structure–function analysis of the isolated respiratory center in a histologically well defined substrate at physiological [K+].
Neural Coding by Two Classes of Principal Cells in the Mouse Piriform Cortex
Authors: Suzuki Norimitsu , Bekkers John M.
Published: November 2006

The piriform (or primary olfactory) cortex is a trilaminar structure that is the first cortical destination of olfactory information, receiving monosynaptic input from the olfactory bulb. Here, we show that the main input layer of the piriform cortex, layer II, is dominated by two classes of principal neurons, superficial pyramidal (SP) and semilunar (SL) cells, with strikingly different properties. Action potentials in SP cells are followed by a Ni2+-sensitive afterdepolarization that promotes burst firing, whereas SL cells fire nonbursting action potentials that are followed by a powerful afterhyperpolarization. Synaptic inputs from the olfactory bulb onto SP cells exhibit prominent paired-pulse facilitation, which is attributable to residual presynaptic Ca2+and a low probability of neurotransmitter release. In contrast, the same inputs onto SL cells do not facilitate. These distinctive synaptic and firing properties cause SP and SL cells to respond differently toin vivo-like bursts of afferent stimulation: SP cells tend to fire bursts of output action potentials at a higher frequency than the input, whereas SL cells tend to fire at a lower frequency than the input. When connected together in the canonical circuit of the piriform cortex, SP and SL cells transform the pattern of synaptic inputs they receive from the olfactory bulb, dispersing the firing rate and latency of output action potentials to an extent that depends on the strength of the input. Thus, the presence of two types of principal cells in layer II of the piriform cortex may underlie coding strategies used for the representation of odors.
Structure of the Catalytic Pore of γ-Secretase Probed by the Accessibility of Substituted Cysteines
Authors: Sato Chihiro , Morohashi Yuichi , Tomita Taisuke , Iwatsubo Takeshi
Published: November 2006

Several single-span membrane proteins are cleaved within their transmembrane domains (TMDs) by intramembrane-cleaving proteases, although the structure of the active site executing intramembrane cleavage remains unknown. Here we use the substituted cysteine accessibility method to examine the structure of presenilin-1, a catalytic subunit of γ-secretase, involved in amyloid β protein generation in Alzheimer's disease and Notch signaling. We show that TMD6 and TMD7 of presenilin-1 contribute to the formation of a hydrophilic pore within the membrane. Residues at the luminal portion of TMD6 are predicted to form a subsite for substrate or inhibitor binding on the α-helix facing a hydrophilic milieu, whereas those around the GxGD catalytic motif within TMD7 are highly water accessible, suggesting formation of a hydrophilic structure within the pore. Collectively, our data suggest that the active site of γ-secretase resides in a catalytic pore filled with water within the lipid bilayer and is tapered around the catalytic aspartates.
α-Synuclein Overexpression in PC12 and Chromaffin Cells Impairs Catecholamine Release by Interfering with a Late Step in Exocytosis
Authors: Larsen Kristin E. , Schmitz Yvonne , Troyer Matthew D. , Mosharov Eugene , Dietrich Paula , Quazi Abrar Z. , Savalle Magali , Nemani Venu , Chaudhry Farrukh A. , Edwards Robert H. , Stefanis Leonidas , Sulzer David
Published: November 2006

α-Synuclein (α-syn), a protein implicated in Parkinson's disease pathogenesis, is a presynaptic protein suggested to regulate transmitter release. We explored how α-syn overexpression in PC12 and chromaffin cells, which exhibit low endogenous α-syn levels relative to neurons, affects catecholamine release. Overexpression of wild-type or A30P mutant α-syn in PC12 cell lines inhibited evoked catecholamine release without altering calcium threshold or cooperativity of release. Electron micrographs revealed that vesicular pools were not reduced but that, on the contrary, a marked accumulation of morphologically “docked” vesicles was apparent in the α-syn-overexpressing lines. We used amperometric recordings from chromaffin cells derived from mice that overexpress A30P or wild-type (WT) α-syn, as well as chromaffin cells from control and α-syn null mice, to determine whether the filling of vesicles with the transmitter was altered. The quantal size and shape characteristics of amperometric events were identical for all mouse lines, suggesting that overexpression of WT or mutant α-syn did not affect vesicular transmitter accumulation or the kinetics of vesicle fusion. The frequency and number of exocytotic events per stimulus, however, was lower for both WT and A30P α-syn-overexpressing cells. The α-syn-overexpressing cells exhibited reduced depression of evoked release in response to repeated stimuli, consistent with a smaller population of readily releasable vesicles. We conclude that α-syn overexpression inhibits a vesicle “priming” step, after secretory vesicle trafficking to “docking” sites but before calcium-dependent vesicle membrane fusion.
Coprecipitation of thorium and lanthanum with UO2+x(s) as host phase
Authors: Rousseau Gurvan , Fattahi Massoud , Grambow Bernd , Boucher F. , Ouvrard G.
Published: November 2006

Coprecipitation may be a significant process in controlling radionuclide release during spent fuel dissolution/reprecipitation in a breached geological disposal site by water. The objective of this work was to study the coprecipitation of thorium and lanthanum with UO2+x(s) as host phase under reducing conditions (pure N2andEh=−300 mV/SHE) as a function of pH and [Th]/[U+Th] or [La]/[U+La] initial concentration ratios. At pH values between 3 to 9, the final concentrations of dissolved Th and La were found to be considerably lower than expected if pure phases, Th(OH)4(s) and La(OH)3(s) would have been formed. Coprecipitation phenomena and formation of solid solutions ThyU1-yO2+x′(s) and (U,La)O2+x′(s) are suggested to be responsible for the lower solubility.
Potentiometric investigations on the interaction of humic acid with Cu(II) and Eu(III) ions
Authors: Kolokassidou Constantina , Pashalidis Ioannis
Published: November 2006

The interaction of Cu(II) and Eu(III) ions with humic acid has been studied by potentiometry under normal atmospheric conditions at pH 6,I=0.1 M (NaClO4) at room temperature (23±2 °C). The investigation was performed for the Cu(II) ion directly by means of a Cu2+ion selective electrode, whereas for the Eu(III) ion it was indirectly based on competition reactions between the Cu(II) ion and the Eu(III) ion. The evaluation of the conditional formation constants, which was based on the charge neutralization model, resulted in as follows:

logβ(Cu-HA(II)) = 5.6±0.3

logβ(Eu-HA(III)) = 6.2±0.5
Reduction behavior of uranium in the presence of citric acid
Authors: Suzuki Yoshinori , Nankawa T. , Yoshida T. , Ozaki Takuo , Ohnuki T. , Francis Arokiasamy J. , Tsushima S. , Enokida Y. , Yamamoto I.
Published: November 2006

We examined the reduction behavior of UO22+in citrate media at pH 2.0−7.0 by column electrodes. At pH 2.0, UO22+was reduced to U(IV) through a one-step reduction process, while it was reduced to U(IV) through a two-step reduction process at pH 3.0−5.0. The reduction potential of UO22+shifted to lower values with an increase in pH from 2.0 to 7.0. At pH 6.0 and 7.0, UO22+was not reduced to U(IV) completely at the electrode potential above -0.8 Vvs. silver/silver chloride electrode. Ultraviolet-visible spectroscopy and speciation calculation of UO22+in citrate media indicated that uranium existed as a mixture of UO22+, [UO2Cit]-and [(UO2)2Cit2]2-at pH 2−3, and a predominant species at pH 3−5 was [(UO2)2Cit2]2-(H3Cit: citric acid). At pH 5−7, polymeric complexes, probably, [(UO2)3Cit3]3-and [(UO2)6Cit6(OH)10]16-were present. These findings suggest that the reduction of UO22+is more difficult by polymerization of UO22+with citric acid at higher pHs. Absorption spectra of the reduced complexes showed that U(IV) forms soluble complexes with citric acid at pH 2.0−5.0, and presence of U(V) species was not observed during the reduction of UO22+.
Interaction of U(VI) with pyrite, galena and their mixtures: a theoretical and multitechnique approach
Authors: Aubriet Hugues , Humbert Bernard , Perdicakis Michel
Published: November 2006

Pyrite and/or galena particles previously conditioned with U(VI) at pH 6 have been characterized by micro-Raman spectrometry, voltammetry, scanning electron microscopy and high resolution X-ray photoelectron spectroscopy. U3O8 is first formed on the sulphide surfaces via a redox process, then, if an excess of U(VI) remains in solution it is sorbed as UO3 and shoepite. Galvanic phenomena occur when the minerals are in mixture in a medium containing U(VI): galena particles are oxidized whereas U(VI) is reduced at the pyrite particle surface. The maximum amounts of fixed uranium are 0.4 mmol/g for pyrite and 0.1 mmol/g for galena and the 50:50 pyrite:galena mixture.
The INE-Beamline for actinide research at ANKA
Authors: Rothe Jörg , Denecke Melissa A. , Dardenne K. , Fanghänel Thomas
Published: November 2006

The Institut für Nukleare Entsorgung (INE) at the Forschungszentrum Karlsruhe (FZK), Germany, has constructed and is operating a beamline at the synchrotron source ANKA dedicated to actinide speciation investigations related to nuclear waste disposal as well as applied and basic actinide research. Experiments on nuclides not suited as nuclear fuel with activities up to 106 times the limit of exemption inside a safe and flexible containment concept are now possible. The design is for a multi-purpose beamline, i.e., a number of methods (XAFS, surface sensitive and spatially resolved techniques) are envisaged on one and the same sample, with X-ray energies from 2472 eV (SK edge) to 23220 eV (RhK edge). The commissioning of the INE-Beamline was officially completed in September 2005 and meanwhile regular user operation has been started. Here we present a description of this new facility and examples for X-ray absorption studies on actinides and homologues performed during the beamline commissioning phase.
Effects of ionic strength on the coordination of Eu(III) and Cm(III) to a Gram-negative bacterium,Paracoccus denitrificans
Authors: Ozaki Takuo , Kimura Takaumi , Ohnuki T. , Francis Arokiasamy J.
Published: November 2006

We studied the effect of ionic strength on the interactions of Europium(III) and Curium(III) with a Gram-negative bacteriumParacoccus denitrificans. Bacterial cells grown in 0.5-, 3.5-, and 5.0% NaCl were used in adsorption experiments and laser experiments that were performed at the same ionic strengths as those in the original growth media. The distribution ratio (logKd) for Eu(III) and Cm(III) was determined at pHs 3−5. To elucidate the coordination environment of Eu(III) adsorbed onP. denitrificans, we estimated the number of water molecules in the inner sphere and strength of the ligand field by time-resolved laser-induced fluorescence spectroscopy (TRLFS) at pHs 4−6. The logKdof Eu(III) and Cm(III) increased with an increase of pH at all ionic strengths because there was less competition for ligands in cells with H+at higher pHs, wherein less H+was present in solution: cation adsorption generally occurs through an exchange with H+on the functional groups of coordination sites. No significant differences were observed in the logKdof Eu(III) and Cm(III) at each pH in 0.5-, 3.5-, and 5.0% NaCl solutions, though competition for ligands with Na+would be expected to increase at higher NaCl concentrations. The logKdof Eu(III) was almost equivalent to that of Cm(III) under all the experimental conditions. TRLFS showed that the coordination environments of Eu(III) did not differ from each other at 0.5-, 3.5-, and 5.0% NaCl at pHs 4−6. TRLFS also showed that the characteristic of the coordination environment of Eu(III) onP. denitrificanswas similar to that on a halophile,Nesterenkonia halobia, while it significantly differed from that on a non-halophile,Pseudomonas putida. These findings indicate that the number of coordination sites for Eu(III) onP. denitrificans, whose cell surface may have similar structures to that of halophiles, increased with increasing ionic strength, though their structure remained unchanged.
Iodination of humic acid samples from different origins
Authors: Reiller Pascal , Mercier-Bion Florence , Gimenez Nicolas , Barré N. , Miserque F.
Published: November 2006

The iodination of Gorleben and synthetic humic substances (HS) was studied complementarily by UV-visible and X-ray Photoelectron Spectroscopy (XPS). The I2(aq) consumption kinetics could neither be linearly correlated to [H+] nor to HS concentration as already observed in the literature. Nevertheless, the electrophilic substitution mechanism was further evidenced by the production of both I3
- and I-, leading to a covalent bonding. The XPS analysis of the iodinated samples confirmed the covalent bonding between iodine and carbon of HS for all the samples.
The fate of the epsilon phase (Mo-Ru-Pd-Tc-Rh) in the UO2 of the Oklo natural fission reactors
Authors: Utsunomiya Satoshi , Ewing Rodney C.
Published: November 2006

In spent nuclear fuel (SNF), the micrometer- to nanometer-sized epsilon phase (Mo-Ru-Pd-Tc-Rh) is an important host of 99Tc which has a long half life (2.13×105 years) and can be an important contributor to dose in safety assessments of nuclear waste repositories. In order to examine the occurrence and the fate of the epsilon phase during the corrosion of SNF over long time periods, samples of uraninite from the Oklo natural reactors (∼ 2.0 Ga) have been investigated using transmission electron microscopy (TEM). Because essentially all of the 99Tc has decayed to 99Ru, this study focuses on 4d-elements of the epsilon phase. Samples were obtained from the research collection at University of Michigan representing reactor zone (RZ) 10 (836, 819, 687) and from RZ 13 (864, 910).

Several phases with 4d-metals have been identified within UO2 matrix at the scale of 50−700 nm; froodite, PdBi2, with trace amounts of As, Fe, and Te, and palladodymite or rhodarsenide, (Pd,Rh)2As. The most abundant 4d-metal phase is ruthenarsenite, (Ru,Ni)As, which has a representative composition: As, 59.9; Co, 2.5; Ni, 5.2; Ru, 18.6; Rh, 8.4; Pd, 3.1; Sb, 2.4 in atomic %. Ruthenarsenite nanoparticles are typically surrounded by Pb-rich domains, galena in most cases; whereas, some particles reveal a complexly zoned composition within the grain, such as a Pb-rich domain at the core and enrichment of Ni, Co, and As at the rim.

Some ruthenarsenites and Rh-Bi-particles are embedded in surrounding alteration products, e.g., chlorite, adjacent to uraninite (no further than ∼5 μm). A few of those particles are still coated by a Pb-rich layer. Based on these results, the history that epsilon phases have experienced can be described as follows: (i) The original epsilon phase was changed to, in most cases, ruthenarsenite, by As-rich fluids with other trace metals. Dissolution and a simultaneous precipitation may be responsible for the phase change. (ii) All Mo and most of the Tc were released from the epsilon phase. Galena precipitated surrounding the 4d-metal phases. (iii) Once the uraninite matrix has dissolved, the epsilon nanoparticles were released and “captured” within alteration phases that are immediately adjacent to the uraninite.