bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical biosensor based on whispering gallery mode excitations in clusters of microparticles
Authors: Francois Alexandre , Himmelhaus Michael
Published: April 2008

A new concept for an optical biosensor based on whispering gallery mode (WGM) excitations in clusters of spherical microresonators is presented. Clusters of microresonators offer the advantage to exhibit specific WGM spectra that can be considered as their fingerprint. Therefore, individual clusters can be traced throughout an experiment even without knowledge of their precise positions. Polyelectrolyte adsorption onto clusters of 10μm polystyrene spheres is monitored in situ. It is shown that the WGMs shift to the same amount as those of a single microresonator and thus sensitivity does not depend on the number of microresonators present in the cluster.
Frequency modulated torsional resonance mode atomic force microscopy on polymers
Authors: Yurtsever Ayhan , Gigler Alexander M. , Dietz Christian , Stark Robert W.
Published: April 2008

In-plane mechanics of polymers can be probed by integrating frequency modulation and torsional resonance mode atomic force microscopy. We investigated a thin film of polystyrene-block-polybutadiene diblock copolymer. To gain more insight into image contrast formation, we examined displacement curves on polystyrene homopolymer surfaces of different molecular weights focusing on energy dissipation and frequency shift. Data suggest that the transition from a highly motile surface layer to the bulk material depends on the molecular weight of the polymer. This, in turn, indicates that the tip is slightly oscillating within the sample surface during imaging.
Experimental demonstration of multiwatt continuous-wave supercontinuum tailoring in photonic crystal fibers
Authors: Kudlinski A. , Bouwmans G. , Quiquempois Y. , Mussot A.
Published: April 2008

We experimentally demonstrate that the spectral broadening of continuous-wave supercontinuum can be controlled by using photonic crystal fibers with two zero-dispersion wavelengths pumped by a fiber laser at 1064nm. The spectrum is bounded by two dispersive waves whose spectral location depends on the two zero-dispersion wavelengths of the fiber. The bandwidth of the generated spectrum and the spectral power density may thus be tailored for particular applications, such as high-resolution optical coherence tomography or optical spectroscopy.
Effects of AlAs interfacial layer on material and optical properties of GaAs∕Ge(100) epitaxy
Authors: Chia C. K. , Dong J. R. , Chi D. Z. , Sridhara A. , Wong A. S. W. , Suryana M. , Dalapati G. K. , Chua S. J. , Lee S. J.
Published: April 2008

Ga As ∕ Al As ∕ Ge ( 100 ) samples grown at 650°C with AlAs interfacial layer thickness of 0, 10, 20, and 30nm were characterized using transmission electron microscopy, secondary ion mass spectrometry (SIMS), and photoluminescence (PL) techniques. SIMS results indicate that the presence of an ultrathin AlAs interfacial layer at the GaAs∕Ge interface has dramatically blocked the cross diffusion of Ge, Ga, and As atoms, attributed to the higher Al–As bonding energy. The optical quality of the GaAs epitaxy with a thin AlAs interfacial layer is found to be improved with complete elimination of PL originated from Ge-based complexes, in corroboration with SIMS results.
Developmental and physiological traits associated with high yield and stay-green phenotype in wheat
Authors: Christopher J. T. , Manschadi A. M. , Hammer G. L. , Borrell A. K.
Published: April 2008

Water availability is a key limiting factor in wheat production in the northern grain belt of Australia. Varieties with improved adaptation to such conditions are actively sought. The CIMMYT wheat line SeriM82 has shown a significant yield advantage in multi-environment screening trials in this region. The objective of this study was to identify the physiological basis of the adaptive traits underpinning this advantage. Six detailed experiments were conducted to compare the growth, development, and yield of SeriM82 with that of the adapted cultivar, Hartog. The experiments were undertaken in field environments that represented the range of moisture availability conditions commonly encountered by winter crops grown on the deep Vertosol soils of this region. The yield of SeriM82 was 6–28% greater than that of Hartog, and SeriM82 exhibited a stay-green phenotype by maintaining green leaf area longer during the grain-filling period in all environments where yield was significantly greater than Hartog. However, where the availability of deep soil moisture was limited, SeriM82 failed to exhibit significantly greater yield or to express the stay-green phenotype. Thus, the stay-green phenotype was closely associated with the yield advantage of SeriM82. SeriM82 also exhibited higher mean grain mass than Hartog in all environments. It is suggested that small differences in water use before anthesis, or greater water extraction from depth after anthesis, could underlie the stay-green phenotype. The inability of SeriM82 to exhibit stay-green and higher yield where deep soil moisture was depleted indicates that extraction of deep soil moisture is important.
Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control
Authors: Pan Meihui , Maitin Vatsala , Parathath Sajesh , Andreo Ursula , Lin Sharron X. , Germain Carly St. , Yao Zemin , Maxfield Frederick R. , Williams Kevin Jon , Fisher Edward A.
Published: April 2008

Hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER pre secretory proteolysis (PERPP), that is increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). We now report the molecular processes by which PUFA-derived ROS regulate PERPP of apoB. ApoB exits the ER; undergoes limited oxidant-dependent aggregation; and then, upon exit from the Golgi, becomes extensively oxidized and converted into large aggregates. The aggregates slowly degrade by an autophagic process. None of the oxidized, aggregated material leaves cells, thereby preventing export of apoB-lipoproteins containing potentially toxic lipid peroxides. In summary, apoB secretory control via PERPP/autophagosomes is likely a key component of normal and pathologic regulation of plasma apoB levels, as well as a means for remarkably late-stage quality control of a secreted protein.
Massive global ozone loss predicted following regional nuclear conflict
Authors: Mills Michael J. , Toon Owen B. , Turco Richard P. , Kinnison Douglas E. , Garcia Rolando R.
Published: April 2008

We use a chemistry-climate model and new estimates of smoke produced by fires in contemporary cities to calculate the impact on stratospheric ozone of a regional nuclear war between developing nuclear states involving 100 Hiroshima-size bombs exploded in cities in the northern subtropics. We find column ozone losses in excess of 20% globally, 25–45% at midlatitudes, and 50–70% at northern high latitudes persisting for 5 years, with substantial losses continuing for 5 additional years. Column ozone amounts remain near or <220 Dobson units at all latitudes even after three years, constituting an extratropical “ozone hole.” The resulting increases in UV radiation could impact the biota significantly, including serious consequences for human health. The primary cause for the dramatic and persistent ozone depletion is heating of the stratosphere by smoke, which strongly absorbs solar radiation. The smoke-laden air rises to the upper stratosphere, where removal mechanisms are slow, so that much of the stratosphere is ultimately heated by the localized smoke injections. Higher stratospheric temperatures accelerate catalytic reaction cycles, particularly those of odd-nitrogen, which destroy ozone. In addition, the strong convection created by rising smoke plumes alters the stratospheric circulation, redistributing ozone and the sources of ozone-depleting gases, including N
2
O and chlorofluorocarbons. The ozone losses predicted here are significantly greater than previous “nuclear winter/UV spring” calculations, which did not adequately represent stratospheric plume rise. Our results point to previously unrecognized mechanisms for stratospheric ozone depletion.
Temperature and pressure dependence of protein stability: The engineered fluorescein-binding lipocalin FluA shows an elliptic phase diagram
Authors: Wiedersich Johannes , Köhler Simone , Skerra Arne , Friedrich Josef
Published: April 2008

We have measured the equilibrium constant for the denaturation transition of the engineered fluorescein-binding lipocalin FluA as a function of pressure and temperature, taking advantage of the fact that the ligand's fluorescence is almost fully quenched when complexed with the folded protein, but reversibly reappears on denaturation. From the equilibrium constant as a function of pressure and temperature all of the involved thermodynamic parameters of protein folding, in particular the changes in entropy and volume, compressibility, thermal expansion, and specific heat, were deduced in a global fitting procedure. Assuming that these parameters are independent of temperature and pressure, we can demonstrate from the ratio of Δβ, Δα2, ΔCpthat the phase diagram of protein folding assumes an elliptic shape. Furthermore, we can show that the thermodynamic condition for such an elliptic phase diagram is related to the degree of correlation between the fluctuations of the changes in volume and enthalpy at the phase boundary. For the protein investigated this correlation is low, as generally expected for highly degenerate systems. Our study suggests that the elliptic phase diagram is a consequence of the inherent conformational disorder of proteins and that it may be viewed as the thermodynamic manifestation of the high degeneracy of conformational energies that is characteristic for this class of macromolecules.
Structure of human monoamine oxidase A at 2.2-Å resolution: The control of opening the entry for substrates/inhibitors
Authors: Son Se-Young , Ma Jichun , Kondou Youhei , Yoshimura Masato , Yamashita Eiki , Tsukihara Tomitake
Published: April 2008

The mitochondrial outer membrane-anchored monoamine oxidase (MAO) is a biochemically important flavoenzyme that catalyzes the deamination of biogenic and xenobiotic amines. Its two subtypes, MAOA and MAOB, are linked to several psychiatric disorders and therefore are interesting targets for drug design. To understand the relationship between structure and function of this enzyme, we extended our previous low-resolution rat MAOA structure to the high-resolution wild-type and G110A mutant human MAOA structures at 2.2 and 2.17 Å, respectively. The high-resolution MAOA structures are similar to those of rat MAOA and human MAOB, but different from the known structure of human MAOA [De Colibus L,
et al.
(2005)
Proc Natl Acad Sci USA
102:12684–12689], specifically regarding residues 108–118 and 210–216, which surround the substrate/inhibitor cavity. The results confirm that the inhibitor selectivity of MAOA and MAOB is caused by the structural differences arising from Ile-335 in MAOA vs. Tyr-326 in MAOB. The structures exhibit a C-terminal transmembrane helix with clear electron density, as is also seen in rat MAOA. Mutations on one residue of loop 108–118, G110, which is far from the active center but close to the membrane surface, cause the solubilized enzyme to undergo a dramatic drop in activity, but have less effect when the enzyme is anchored in the membrane. These results suggest that the flexibility of loop 108–118, facilitated by anchoring the enzyme into the membrane, is essential for controlling substrate access to the active site. We report on the observation of the structure–function relationship between a transmembrane helical anchor and an extra-membrane domain.
Human cremation in Mexico 3,000 years ago
Authors: Duncan William N. , Balkansky Andrew K. , Crawford Kimberly , Lapham Heather A. , Meissner Nathan J.
Published: April 2008

Mixtec nobles are depicted in codices and other proto-historic documentation taking part in funerary rites involving cremation. The time depth for this practice was unknown, but excavations at the early village site of Tayata, in the southern state of Oaxaca, Mexico, recovered undisturbed cremation burials in contexts dating from the eleventh century B.C. These are the earliest examples of a burial practice that in later times was reserved for Mixtec kings and Aztec emperors. This article describes the burial contexts and human remains, linking Formative period archaeology with ethnohistorical descriptions of Mixtec mortuary practices. The use of cremation to mark elevated social status among the Mixtec was established by 3,000 years ago, when hereditary differences in rank were first emerging across Mesoamerica.
Small-molecule agonists and antagonists of F-box protein–substrate interactions in auxin perception and signaling
Authors: Hayashi Ken-ichiro , Tan Xu , Zheng Ning , Hatate Tatsuya , Kimura Yoshio , Kepinski Stefan , Nozaki Hiroshi
Published: April 2008

The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. We have shown that the
Arabidopsis
F-box protein TIR1 is a receptor for auxin, and our recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin–ligase complex SCF
TIR1
. Auxin binding enhances the interaction between TIR1 and its substrates, the Aux/IAA repressors, thereby promoting the ubiquitination and degradation of Aux/IAAs, altering the expression of hundreds of genes. TIR1 is the prototype of a new class of hormone receptor and the first example of an SCF ubiquitin-ligase modulated by a small molecule. Here, we describe the design, synthesis, and characterization of a series of auxin agonists and antagonists. We show these molecules are specific to TIR1-mediated events in
Arabidopsis
, and their mode of action in binding to TIR1 is confirmed by x-ray crystallographic analysis. Further, we demonstrate the utility of these probes for the analysis of TIR1-mediated auxin signaling in the moss
Physcomitrella patens.
Our work not only provides a useful tool for plant chemical biology but also demonstrates an example of a specific small-molecule inhibitor of F-box protein–substrate recruitment. Substrate recognition and subsequent ubiquitination by SCF-type ubiquitin ligases are central to many cellular processes in eukaryotes, and ubiquitin-ligase function is affected in several human diseases. Our work supports the idea that it may be possible to design small-molecule agents to modulate ubiquitin-ligase function therapeutically.
Spectral completion of partially masked sounds
Authors: McDermott Josh H. , Oxenham Andrew J.
Published: April 2008

Natural environments typically contain multiple sound sources. The sounds from these sources frequently overlap in time and often mask each other. Masking could potentially distort the representation of a sound's spectrum, altering its timbre and impairing object recognition. Here, we report that the auditory system partially corrects for the effects of masking in such situations, by using the audible, unmasked portions of an object's spectrum to fill in the inaudible portions. This spectral completion mechanism may help to achieve perceptual constancy and thus aid object recognition in complex auditory scenes.
Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes
in vivo
Authors: Kalyuzhniy O. , Di Paolo N. C. , Silvestry M. , Hofherr S. E. , Barry M. A. , Stewart P. L. , Shayakhmetov D. M.
Published: April 2008

Human species C adenovirus serotype 5 (Ad5) is the most common viral vector used in clinical studies worldwide. Ad5 vectors infect liver cells
in vivo
with high efficiency via a poorly defined mechanism, which involves virus binding to vitamin K-dependent blood coagulation factors. Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity of 229 pM. This affinity is 40-fold stronger than the reported affinity of Ad5 fiber for the cellular receptor coxsackievirus and adenovirus receptor, CAR. Cryoelectron microscopy and single-particle image reconstruction revealed that the FX attachment site is localized to the central depression at the top of the hexon trimer. Hexon-mutated virus bearing a large insertion in hexon showed markedly reduced FX binding
in vitro
and failed to deliver a transgene to hepatocytes
in vivo
. This study describes the mechanism of FX binding to Ad5 and demonstrates the critical role of hexon for virus infection of hepatocytes
in vivo
.
A polycatenated DNA scaffold for the one-step assembly of hierarchical nanostructures
Authors: Weizmann Yossi , Braunschweig Adam B. , Wilner Ofer I. , Cheglakov Zoya , Willner Itamar
Published: April 2008

A unique DNA scaffold was prepared for the one-step self-assembly of hierarchical nanostructures onto which multiple proteins or nanoparticles are positioned on a single template with precise relative spatial orientation. The architecture is a topologically complex ladder-shaped polycatenane in which the “rungs” of the ladder are used to bring together the individual rings of the mechanically interlocked structure, and the “rails” are available for hierarchical assembly, whose effectiveness has been demonstrated with proteins, complementary DNA, and gold nanoparticles. The ability of this template to form from linear monomers and simultaneously bind two proteins was demonstrated by chemical force microscopy, transmission electron microscopy, and confocal fluorescence microscopy. Finally, fluorescence resonance energy transfer between adjacent fluorophores confirmed the programmed spatial arrangement between two different nanomaterials. DNA templates that bring together multiple nanostructures with precise spatial control have applications in catalysis, biosensing, and nanomaterials design.
Incorrect nucleotide insertion at the active site of a G:A mismatch catalyzed by DNA polymerase β
Authors: Lin Ping , Batra Vinod K. , Pedersen Lars C. , Beard William A. , Wilson Samuel H. , Pedersen Lee G.
Published: April 2008

Based on a recent ternary complex crystal structure of human DNA polymerase β with a G:A mismatch in the active site, we carried out a theoretical investigation of the catalytic mechanism of incorrect nucleotide incorporation using molecular dynamics simulation, quantum mechanics, combined quantum mechanics, and molecular mechanics methods. A two-stage mechanism is proposed with a nonreactive active-site structural rearrangement prechemistry step occurring before the nucleotidyl transfer reaction. The free energy required for formation of the prechemistry state is found to be the major factor contributing to the decrease in the rate of incorrect nucleotide incorporation compared with correct insertion and therefore to fidelity enhancement. Hence, the transition state and reaction barrier for phosphodiester bond formation after the prechemistry state are similar to that for correct insertion reaction. Key residues that provide electrostatic stabilization of the transition state are identified.
Language universals in human brains
Authors: Berent Iris , Lennertz Tracy , Jun Jongho , Moreno Miguel A. , Smolensky Paul
Published: April 2008

Do speakers know universal restrictions on linguistic elements that are absent from their language? We report an experimental test of this question. Our case study concerns the universal restrictions on initial consonant sequences, onset clusters (e.g.,blinblock). Across languages, certain onset clusters (e.g.,lb) are dispreferred (e.g., systematically under-represented) relative to others (e.g.,bl). We demonstrate such preferences among Korean speakers, whose language lacks initial C1C2clusters altogether. Our demonstration exploits speakers' well known tendency to misperceive ill-formed clusters. We show that universally dispreferred onset clusters are more frequently misperceived than universally preferred ones, indicating that Korean speakers consider the former cluster-type more ill-formed. The misperception of universally ill-formed clusters is unlikely to be due to a simple auditory failure. Likewise, the aversion of universally dispreferred onsets by Korean speakers is not explained by English proficiency or by several phonetic and phonological properties of Korean. We conclude that language universals are neither relics of language change nor are they artifacts of generic limitations on auditory perception and motor control—they reflect universal linguistic knowledge, active in speakers' brains.
Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease
Authors: Wernig Marius , Zhao Jian-Ping , Pruszak Jan , Hedlund Eva , Fu Dongdong , Soldner Frank , Broccoli Vania , Constantine-Paton Martha , Isacson Ole , Jaenisch Rudolf
Published: April 2008

The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.
A structural–functional basis for dyslexia in the cortex of Chinese readers
Authors: Siok Wai Ting , Niu Zhendong , Jin Zhen , Perfetti Charles A. , Tan Li Hai
Published: April 2008

Developmental dyslexia is a neurobiologically based disorder that affects ≈5–17% of school children and is characterized by a severe impairment in reading skill acquisition. For readers of alphabetic (e.g., English) languages, recent neuroimaging studies have demonstrated that dyslexia is associated with weak reading-related activity in left temporoparietal and occipitotemporal regions, and this activity difference may reflect reductions in gray matter volume in these areas. Here, we find different structural and functional abnormalities in dyslexic readers of Chinese, a nonalphabetic language. Compared with normally developing controls, children with impaired reading in logographic Chinese exhibited reduced gray matter volume in a left middle frontal gyrus region previously shown to be important for Chinese reading and writing. Using functional MRI to study language-related activation of cortical regions in dyslexics, we found reduced activation in this same left middle frontal gyrus region in Chinese dyslexics versus controls, and there was a significant correlation between gray matter volume and activation in the language task in this same area. By contrast, Chinese dyslexics did not show functional or structural (i.e., volumetric gray matter) differences from normal subjects in the more posterior brain systems that have been shown to be abnormal in alphabetic-language dyslexics. The results suggest that the structural and functional basis for dyslexia varies between alphabetic and nonalphabetic languages.
Protein kinase CK2 as an ectokinase: The role of the regulatory CK2β subunit
Authors: Rodriguez Fernando A. , Contreras Carlos , Bolanos-Garcia Víctor , Allende Jorge E.
Published: April 2008

Protein kinase CK2 (also known as casein kinase 2) is present in the cytoplasm, nuclei, and several other organelles. In addition, this enzyme has been found bound to the external side of the cell membrane where it acts as an ectokinase phosphorylating several extracellular proteins. Previous experiments with transfection of HEK-293T cells demonstrated that expression of both subunits, CK2α (catalytic) and CK2β (regulatory), was necessary for the appearance of the ectopic enzyme as an ectokinase. In this work, using deletion and point mutations of CK2β, it was possible to demonstrate that the region between amino acids 20 and 33 was necessary for the export of the enzyme as an ectokinase. Phenylalanines 21 and 22 and acidic residues in positions 26–28 are involved in the structural aspects that are required for export. However, the region encompassing amino acids 20–33 of CK2β is not sufficient to make the carboxyl half of this subunit functional in bringing CK2 to the ectokinase locus. In cells transfected with only CK2β, it was demonstrated that 3–4% of the subunit is exported to the cell medium, but the subunit is not bound to the external membrane.
The Association Between Earlier Marijuana Use and Subsequent Academic Achievement and Health Problems: A Longitudinal Study
Authors: Brook Judith S. , Stimmel Matthew A. , Zhang Chenshu , Brook David W.
Published: April 2008

In this prospective longitudinal study, the authors investigated the association between marijuana use over a period of 13 years and subsequent health problems at age 27. A community sample of 749 participants from upstate New York was interviewed at mean ages of 14, 16, 22, and 27 years. Marijuana use over time was significantly associated with increased health problems by the late twenties, including respiratory problems, general malaise, neurocognitive problems, and lower academic achievement and functioning. Effective prevention and intervention programs should consider the wide range of adverse physiological and psychosocial outcomes associated with marijuana use over time.
Long‐Term Treatment with Buprenorphine/Naloxone in Primary Care: Results at 2–5 Years
Authors: Fiellin David A. , Moore Brent A. , Sullivan Lynn E. , Becker William C. , Pantalon Michael V. , Chawarski Marek C. , Barry Declan T. , O'Connor Patrick G. , Schottenfeld Richard S.
Published: April 2008

To examine long‐term outcomes with primary care office‐based buprenorphine/naloxone treatment, we followed 53 opioid‐dependent patients who had already demonstrated six months of documented clinical stability for 2–5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty‐eight percent of enrolled subjects were retained for two years. Ninety‐one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid‐dependent patients exhibit moderate levels of retention in primary care office‐based treatment.
Predictors of Cardiovascular Response to Methamphetamine Administration in Methamphetamine‐Dependent Individuals
Authors: Fleury Gilles , De La Garza Richard , Mahoney James J. , Evans Sarah E. , Newton Thomas F.
Published: April 2008

The goal of the present investigation was to determine predictors of cardiovascular response to methamphetamine administrated in the laboratory. Heart rate (HR) and blood pressure (BP) were measured at baseline and at several time points following the administration of methamphetamine or saline placebo. One‐way ANOVA was used to determine the differences between female and male subjects in their cardiovascular response. In male subjects, linear regression and one‐way ANOVA were used to determine the influence of potential predictors on cardiovascular response, including age, weight, drug use indicators, concurrent use of other substances, route of administration, and race. Methamphetamine administration provoked significant increases in HR and BP, as compared to placebo. Female gender was associated with larger peak change in diastolic BP following administration. Baseline HR and BP were found to be strong predictors of cardiovascular response to methamphetamine administration in male subjects. Lifetime use and recent use of methamphetamine and nicotine did not predict cardiovascular response to methamphetamine. Recent alcohol use was associated with increased peak change in diastolic BP. Also, current use of cannabis was negatively correlated with peak HR change. Male cannabis users show lower peak change in HR as compared to non‐cannabis users. As compared to methamphetamine smokers, intravenous users demonstrated higher peak change in diastolic BP following drug administration. Race did not have a significant effect on cardiovascular response. Taken together, these findings may help in the prevention and treatment of cardiovascular events in a population at high risk of premature morbidity and mortality.
Identifying Methamphetamine Users at Risk for Major Depressive Disorder: Findings from the Methamphetamine Treatment Project at Three‐Year Follow‐Up
Authors: Glasner‐Edwards Suzette , Mooney Larissa J. , Marinelli‐Casey Patricia , Hillhouse Maureen , Ang Alfonso , Rawson Richard ,   the Methamphetamine Treatment Project Corporate Authors
Published: April 2008

Little is known about risk factors for depression in methamphetamine users. Using data from 526 adults in the largest psychosocial clinical trial of methamphetamine users conducted to date, this study examined clinical, demographic, and substance use characteristics that predict the presence of a diagnosis of major depressive disorder (MDD) three years after treatment for methamphetamine dependence. The results indicate that two risk factors predict a diagnosis of MDD: a Beck Depression Inventory total score greater than 20, and one or more prior suicide attempts. These risk factors identify methamphetamine users who may benefit from early interventions for psychiatric symptoms.
Gender Differences in Mental Health Characteristics and Gambling among African‐American Adolescent Gamblers
Authors: Martins Silvia S. , Storr Carla L. , Ialongo Nicholas S. , Chilcoat Howard D.
Published: April 2008

This study explores gender differences in lifetime and recent substance use/internalizing behavior, childhood externalizing behavior, and gambling preferences among African‐American youth gamblers. Data are from a prospective study of a community sample of 452 urban African‐American youths who began at entry into first grade and were followed for ten years. Gambling was associated with high teacher ratings of childhood externalizing behaviors among males and with high parent ratings of childhood impulsivity and hyperactivity among both genders. Internalizing behavior was associated with female gambling. No male‐female differences in substance use/lifetime conduct disorder among gamblers were noted. Gambling preferences/frequency differed across genders.
Synthetic chemerin-derived peptides suppress inflammation through ChemR23
Authors: Cash Jenna L. , Hart Rosie , Russ Andreas , Dixon John P.C. , Colledge William H. , Doran Joanne , Hendrick Alan G. , Carlton Mark B.L. , Greaves David R.
Published: April 2008

Chemerin is a chemotactic protein that binds to the G protein–coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A140-A154), inhibited macrophage (MΦ) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MΦ chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23−/− mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23.
Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice
Authors: Hill Jonathan A. , Bell David A. , Brintnell William , Yue David , Wehrli Bret , Jevnikar Anthony M. , Lee David M. , Hueber Wolfgang , Robinson William H. , Cairns Ewa
Published: April 2008

Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this disease are not fully characterized, but may involve the loss of tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated that this modification leads to a selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules that carry the RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). We describe the induction of arthritis in DR4-IE transgenic (tg) mice with citrullinated fibrinogen, a protein commonly found in inflamed synovial tissue and a frequent target of autoantibodies in RA patients. The disease induced in these mice was characterized by synovial hyperplasia followed by ankylosis, but lacked a conspicuous polymorphonuclear cell infiltrate. Immunological analysis of these mice through T cell epitope scanning and antibody microarray analysis identified a unique profile of citrulline-specific reactivity that was not found in DR4-IE tg mice immunized with unmodified fibrinogen or in wild-type C57BL/6 mice immunized with citrullinated fibrinogen, two conditions where arthritis was not observed. These observations directly implicate citrullinated fibrinogen as arthritogenic in the context of RA-associated MHC class II molecules.
Requirements for alignment of electron cyclotron current drive for neoclassical tearing mode stabilization in ITER
Authors: La Haye R.J. , Ferron J.R. , Humphreys D.A. , Luce T.C. , Petty C.C. , Prater R. , Strait E.J. , Welander A.S.
Published: April 2008

ITER will rely on electron cyclotron stabilization of neoclassical tearing mode islands. The large size and low torque applied in ITER imply slow plasma rotation and susceptibility to island locking by the resistive wall; locking is likely to lead to a loss of the high confinement H-mode, a beta collapse and possibly disruption. ‘Front’ steering of the launcher, with narrower electron cyclotron current drive (ECCD), has resolved the issue in ‘remote’ steering of the driven current being too broad and relatively ineffective. However, narrower current drive places demands on alignment of the current drive on the rational surface that is being stabilized. DIII-D alignment techniques with and without (preemptive) an island are reviewed. The results are used to check models for the effect of misalignment and are then applied to ITER. Criteria for accuracy of alignment as a function of injected power and for the necessary time response of the controller are presented.
First experiments of plasma start-up assisted by ECRH on Tore Supra
Authors: Bucalossi J. , Hertout P. , Lennholm M. , Saint-Laurent F. , Bouquey F. , Darbos C. , Traisnel E. , Trier E.
Published: April 2008

ECRH pre-ionization and assisted start-up will be necessary in ITER due to the low electric field available (⩽0.3 V m−1). This paper reports on the results recently obtained on assisted start-up at the fundamental EC resonance on the tokamak Tore Supra (BT= 3.85 T,R= 2.4 m,a= 0.72). The Tore Supra ECRH/ECCD system is based on two 118 GHz gyrotrons (EC resonance atR∼ 2.17 m). The power is injected into the plasma as Gaussian beams by an antenna located on the low field side which, using actively cooled mirrors inside the vacuum vessel, allows extensive control of both poloidal and toroidal injection angles. During the last experimental campaign, the ECRH system has been used for the first time to assist the plasma start-up. The usual start-up voltage on Tore Supra is 25 V (1.7 V m−1) with deuterium prefill pressure of around 20 mPa. The minimum stray field value (B⊥) in most of the vacuum vessel is lower than 5 mT, which gives toroidal connection lengths (a0BT/B⊥) longer than 770 m. In these conditions, attempts have been made to lower the start-up voltage. Sustained breakdowns were obtained down to ∼0.4 V m−1without external assistance at 5 mPa. Besides, ∼300 kW of ECRH has been applied during 50 ms (one gyrotron in O-mode). Pre-ionization was successfully achieved at the resonance location and ∼30 kA of current was established in 10 ms. Successful plasma initiation has been obtained down to ∼0.28 V m−1at 5 mPa.
New upper bounds for kissing numbers from semidefinite programming
Authors: Bachoc Christine , Vallentin Frank
Published: April 2008

Recently A. Schrijver derived new upper bounds for binary codes using semidefinite programming. In this paper we adapt this approach to codes on the unit sphere and we compute new upper bounds for the kissing number in several dimensions. In particular our computations give the (known) values for the cases

n
=
3
,
4
,
8
,
24

n = 3, 4, 8, 24

.
The dynamics of pseudographs in convex Hamiltonian systems
Authors: Bernard Patrick
Published: April 2008

We study the evolution, under convex Hamiltonian flows on cotangent bundles of compact manifolds, of certain distinguished subsets of the phase space. These subsets are generalizations of Lagrangian graphs, which we call pseudographs. They emerge in a natural way from Fathi’s weak KAM theory. By this method, we find various orbits which connect prescribed regions of the phase space. Our study was inspired by works of John Mather. As an application, we obtain the existence of diffusion in a large class of a priori unstable systems and provide a solution to the large gap problem. We hope that our method will have applications to more examples.

Résumé. Nous étudions l’évolution, par le flot d’un Hamiltonien convexe sur une variété compacte, de certains ensembles de l’espace des phases. Nous appelons pseudographes ces ensembles, qui sont des généralisations de graphes Lagrangiens apparaissant de manière naturelle dans la théorie KAM faible de Fathi. Par cette méthode, nous trouvons diverses orbites qui joignent des domaines donnés de l’espace des phases. Notre étude s’inspire de travaux de John Mather. Nous obtenons l’existence de diffusion dans une large classe de systèmes à priori instables comme application de cette méthode, qui permet de résoudre le probleme de l’écart entre les tores invariants. Nous espérons que la méthode s’appliquera à d’autres exemples.
Singularly perturbed elliptic systems and multi-valued harmonic functions with free boundaries
Authors: Caffarelli L. , Lin Fang-Hua
Published: April 2008

Here we study the asymptotic limits of solutions of some singularly perturbed elliptic systems. The limiting problems involve multiple valued harmonic functions or, in general, harmonic maps to singular spaces and free interfaces between supports of various components of the maps. The main results of the paper are the uniform Lipschitz regularity of solutions as well as the regularity of free interfaces.
Infinite finitely generated fields are biinterpretable with ℕ
Authors: Scanlon Thomas
Published: April 2008

Using the work of several other mathematicians, principally the results of Poonen refining the work of Pop that algebraic independence is definable within the class of finitely generated fields and of Rumely that the ring of rational integers is uniformly interpreted in global fields, and a theorem on the definability of valuations on function fields of curves, we show that each infinite finitely generated field considered in the ring language is parametrically biinterpretable withN\mathbb {N}. As a consequence, for any finitely generated field there is a first-order sentence in the language of rings which is true in that field but false in every other finitely generated field and, hence, Pop’s conjecture that elementarily equivalent finitely generated fields are isomorphic is true.
Early stages of protein crystallization as revealed by emerging optical waveguide technology
Authors: Boudjemline Attia , Clarke David T. , Freeman Neville J. , Nicholson James M. , Jones Gareth R.
Published: April 2008

A highly sensitive method for studying the onset of protein crystallization in real time using an optical-waveguide-based technique is reported. Dual polarization interferometry uses light from sensing and reference waveguides to produce an interference pattern, which when the sensing waveguide is immersed in a protein solution supplies information on the thickness and density of any protein adlayer on the sensing waveguide's surface. This technique provides evidence that crystallization proceedsvialarge protein aggregates but, more strikingly, shows dramatic light loss from the sensing waveguide at a very early stage during crystallization. The technique proves relatively insensitive to the crystallization of small molecules or poorly formed protein crystals and affords a method of distinguishing crystal formation from the formation of other protein aggregates or salt crystals. The experimental setup currently necessitates crystallization using the batch method, and precipitant mixing at high supersaturation is known to introduce a greater variability compared with methods such as vapour diffusion or dialysis, but first results promise to bridge the paucity of real-time methods available to distinguish the onset of protein crystallization from other forms of aggregation.
Structure of K2TaF7at 993 K: the combined use of synchrotron powder data and solid-state DFT calculations
Authors: Smrčok Ľubomír , Brunelli Michela , Boča Miroslav , Kucharík Marian
Published: April 2008

The structure of dipotassium tantalum heptafluoride, K2TaF7, was optimized by energy minimization in the solid state using a plane-waves DFT (density functional theory) computation for which the lattice parameters were obtained by the Le Bail technique from synchrotron X-ray powder diffraction data collected at 993 K. Owing to the sample's corrosiveness, it had to be loaded in a thin-walled Pt capillary. It was found that the structure corresponds to that of the β-K2TaF7phase. The Ta atoms in the TaF7−polyhedra are sevenfold coordinated by fluorine atoms positioned within 1.977–2.007 Å. The K atoms are surrounded by eleven (K1) or eight (K2) fluorine atoms. Every F atom in the structure is surrounded by three K atoms. The F...K contact distances vary from 2.57 to 3.32 Å. It is suggested that solid-state DFT methods may, in many cases, provide an alternative tool to standard Rietveld refinements for structure determination.
Modelling the X-ray powder diffraction of nitrogen-expanded austenite using the Debye formula
Authors: Oddershede Jette , Christiansen Thomas L. , Ståhl Kenny
Published: April 2008

Stress-free and homogeneous samples of nitrogen-expanded austenite, a defect-rich f.c.c. structure with a high interstitial nitrogen occupancy (between 0.36 and 0.61), have been studied using X-ray powder diffraction and Debye simulations. The simulations confirm the presence of deformation stacking faults in the structure, while twin or growth faulting can be ruled out. Screw dislocations are abundant and the dislocation density increases with the interstitial nitrogen occupancy. Whether the N atoms are clustered or distributed randomly among the octahedral interstices was found to be indistinguishable to X-ray powder diffraction.
Modelling on-axis microdiffraction to investigate crystallographic texture within high-performance polymer fibres
Authors: Davies Richard J. , Burghammer Manfred , Riekel Christian
Published: April 2008

Radial crystallographic texture in high-performance polymeric fibres is a common structural feature. Quite why such preferred orientation should exist and how it impacts upon the mechanical properties of the fibre is still not fully understood. This study reports the use of a modelling approach to investigate radial texture in the poly(p-phenylene benzobisoxazole) fibre type. The model allows azimuthal scattering profiles to be calculated corresponding to an on-axis microdiffraction geometry. The results show that, in order to model experimental data successfully, an offset is required between theaunit-cell axis and the fibre radial direction. The origin of this offset is tentatively attributed to solvent outflow during coagulation, which aligns the planar molecular chains. Meanwhile, textural differences between different fibre types can be explained by processing differences.
Time-resolved diffraction studies into the pressure acid leaching of nickel laterite ores: a comparison of laboratory and synchrotron X-ray experiments
Authors: Scarlett Nicola V. Y. , Madsen Ian C. , Whittington Barry I.
Published: April 2008

This paper compares time-resolved diffraction experiments that have been performed using laboratory and synchrotron X-ray sources. The experiments investigated the mechanism and kinetics of pressure acid leaching of nickel laterite ores. The sample environment was a purpose-built capillary reaction vessel, and extensive method development was conducted in the laboratory using Mo Kα radiation prior to repeating and extending the experiments at the Daresbury Synchrotron Radiation Source, beamline MPW6.2. In general, the synchrotron results confirmed the findings from previously reported laboratory work and also confirmed the presence of a minor phase that had been ambiguous in the laboratory experiments,i.e.the formation of hematite in the pressure acid leaching of saprolite. The synchrotron measurements also extended the experimental programme to include poorly diffracting laterite components that could not be examined in the laboratory,e.g.nontronite. The results from these components supported the reaction mechanisms determined fromex-situanalyses conducted in larger scale autoclaves.
CHAINSAW: a program for mutating pdb files used as templates in molecular replacement
Authors: Stein Norman
Published: April 2008

CHAINSAWis a model editing program for use in molecular replacement. Given a sequence alignment between template and target, it modifies the template structure on a residue-by-residue basis by pruning nonconserved residues while leaving conserved residues unchanged. Three degrees of pruning are possible. An internal alignment algorithm is used to cope with any residues that may be missing from the X-ray structure.CHAINSAWhas been successfully used as a tool to assist in solving a number of protein structures.
Imaging of interstitial atoms in Ga1−xMnxAs layers by means of X-ray diffuse scattering
Authors: Kopecký Miloš , Busetto Edoardo , Lausi Andrea , Šourek Zbyněk , Kub Jiří , Cukr Miroslav , Novák Vít , Olejník Kamil , Wright Jonathan P.
Published: April 2008

The local atomic structure of a Ga1−xMnxAs (x= 0.07) layer during the annealing process was studied by means of X-ray diffuse scattering. The difference between the pair-distribution functions before and after annealing indicated the fraction of atoms that changed concentration and identified them to be exclusively interstitial atoms at the centres of gallium and/or arsenic tetrahedra in the GaMnAs unit cell.