bluuebunny/crossref_metadata_2025 huggingface dataset:
No Wheelchairs Beyond this Point: A Historical Examination of Wheelchair Access in the Twentieth Century in Britain and America
Authors: Watson Nick , Woods Brian
Published: January 2005

On the surface, the wheelchair appears a simple machine: its function seemingly apparent and its workings relatively uncomplicated. Yet, despite this apparent simplicity, the wheelchair is a complex artefact imbued with a myriad of social as well as technical relations that act simultaneously to exclude and include, confine and liberate, shape and be shaped. The wheelchair's inextricable links to injury and illness have certainly shaped its definition as a medical device. Such a definition has labelled the occupier as passive or ill and shaped a wider understanding of the machine as a prison. Wheelchair users, however, perceive the machine as a means to independence: it enables rather than disables. We present evidence here to suggest that this is not a recent phenomenon as we show how wheelchair access has been on the political agenda for disabled people for most of the twentieth century. The paper also examines the role of the wheelchair in the development of this movement, and we suggest that, as the design of the wheelchair improved, so the demand for better access increased. The final section of the paper looks at how poorly the state and its agents understood the issue of access.
Regional climate and glacial control on high‐resolution oxygen isotope records from Ain el Beida (latest Miocene, northwest Morocco): A cyclostratigraphic analysis in the depth and time domain
Authors: van der Laan E. , Gaboardi S. , Hilgen F. J. , Lourens L. J.
Published: January 2005

High‐resolution benthic and planktonic stable oxygen isotope records are presented for the upper Miocene Ain el Beida (AEB) section in northwestern Morocco and reveal the clear imprint of the (climatic) precession, obliquity, and eccentricity cycles in the interval between 6.5 and 5.5 Ma. The δ18O depth series were transformed into time series using astronomical tuning of the sedimentary color cycles to the 65°N summer insolation curve of the La93 solution with present‐day values for tidal dissipation and dynamical ellipticity. Spectral analysis and band‐pass filtering show that the ratios of the astronomically related spectral peaks are not consistent in the depth and time domain. The inconsistencies are mainly due to variations in sedimentation rate that are positively correlated with precession amplitude (i.e., modulated by eccentricity). In addition, they result from a long‐term trend in sedimentation rate. A simple model of nonlinear response of the sedimentation rate to the eccentricity modulation of precession was used to simulate the observed shifts in the relative position of the spectral peaks in the depth domain. Cross‐spectral analysis was carried out on the δ18O time series and a combined eccentricity, tilt (obliquity), and precession (ETP) curve. The precession‐controlled δ18O signal varies in‐phase with ETP partly as a result of the tuning procedure, while the obliquity related signal reveals a small lag of 2–3 kyr relative to obliquity. This lag is slightly reduced at the time of the Messinian Salinity Crisis (MSC) and increases to 5–6 kyr if the tidal dissipation term in the astronomical solution is reduced to half its present‐day value. The obliquity‐related lag is most likely associated with the slow buildup of ice caps, whereas the precession signal is interpreted as to dominantly reflect regional climate changes comparable to those associated with Mediterranean sapropels. Finally, the benthic δ18O record is compared with open ocean records and discussed in terms of an astronomically tuned oxygen isotope stratigraphic framework.
Ion composition variations in the plasma sheet observed by Cluster/RAPID
Authors: Ruan P. , Fu S. Y. , Zong Q.‐G. , Pu Z. Y. , Cao X. , Liu W. L. , Zhou X. Z. , Daly P. W.
Published: January 2005

Based on the energetic particle measurements obtained by Cluster/RAPID (Research with Adaptive Particle Imaging Detectors), ion composition variations in the plasma sheet have been investigated. By comparing observations during quiet and storm intervals, it is found that, in addition to the enhanced energy density for all ion species, the ratio of energetic O+ ions to protons shows an increase during geomagnetic active periods in the near‐Earth plasma sheet (−15 RE < X < −12 RE). However, the ratio shows a decrease in the middle plasma sheet (−19 RE < X < −15 RE). These observation results have been further confirmed by a statistical study of all the plasma sheet crossing events from 2001 to 2003. Observations also show that energetic particles embedded in the earthward high‐speed streams observed in the plasma sheet have an obvious low abundance of heavy ions compared with surrounding plasmas. It is implied that energetic O+ ions could be distributed in a limited region in the plasma sheet and much less ionosphere origin particles could reach the region beyond X = −15 RE. Bursty Bulk Flows (BBFs) could not supply more energetic O+ ions to the near‐Earth plasma sheet, whereas the ionospheric supplement, together with local acceleration processes, leads to an enhanced oxygen abundance during active times.
Hydrophilic properties of aged soot
Authors: Zuberi Bilal , Johnson Kirsten S. , Aleks Gretchen K. , Molina Luisa T. , Molina Mario J. , Laskin Alexander
Published: January 2005

The global presence of soot has significant effects on regional and global climate, as well as human health. Influence of soot on radiation budget, rain formation and heterogeneous chemistry, and its residence time in the atmosphere are largely dependent on its ability to interact with water. While freshly emitted soot is extremely hydrophobic, oxidation during aging causes soot to become more hydrophilic. Laboratory studies demonstrate that aged soot attracts and retains water, and can be efficiently removed from the troposphere by entrapment in existing liquid cloud droplets or by activation as cloud condensation nuclei.
On the rheological models used for time‐domain methods of seismic wave propagation
Authors: Moczo Peter , Kristek Jozef
Published: January 2005

After publications by Emmerich and Korn [1987] and Carcione et al. [1988a, 1988b] authors who implemented realistic attenuation in the time‐domain methods decided for either of two rheological models – generalized Maxwell body (as defined by Emmerich and Korn) or generalized Zener body. Two parallel sets of papers and mathematical formalisms developed during the years. We have not found any comments on the other rheology. Therefore, we review both models and show that, in fact, they are equivalent. We also derive material‐independent anelastic functions.
Sharp near‐equatorial transitions in inertial motions and deep‐ocean step‐formation
Authors: van Haren Hans
Published: January 2005

The near‐equatorial region is importantly different from other ocean areas: it acts as a barrier for large‐scale meridional circulation, because the strongest currents are directed East‐West, and it shows weak interior mixing despite large internal wave shear. All seems related to a change in importance of the vertical ‘inertial’ component of the earth's rotation. As rotational effects dominate large‐scale ocean motions through a geostrophic balance, they become negligible at the equator. Here, deep‐ocean observational evidence is presented of hitherto neglected rotational effects. It is demonstrated that when the equator is approached near‐inertial internal wave motions very suddenly rather than smoothly change polarization from near‐circular to near‐rectilinear within half a degree across latitudes ∣φ∣ = 1.5 ± 0.5°. At the same latitudes sudden transitions are observed of large‐scale kinetic energy and small‐scale density stratification variations. Understanding the above requires a non‐traditional approach in which the horizontal component of earth's rotation is considered.
An unusually fast interplanetary coronal mass ejection observed by Ulysses at 5 AU on 15 November 2003
Authors: de Koning Curt A. , Steinberg John T. , Gosling J. T. , Reisenfeld Daniel B. , Skoug Ruth M. , St. Cyr O. C. , Malayeri M. L. , Balogh André , Rees Adam , McComas D. J.
Published: January 2005

On 15 November 2003, at ∼2030 UT, Ulysses/SWOOPS observed the onset of a large, unusually fast interplanetary coronal mass ejection (ICME) in the solar wind at 5.2 AU. Ulysses measured the peak solar wind flow speed associated with this event, vmax = 993 km s−1, in the turbulent sheath region preceding the ICME. This is the fastest solar wind speed recorded by Ulysses/SWOOPS at this distance since November 1992. On 7 November 2003 at 1554 UT, SOHO/LASCO observed the solar counterpart of this ICME behind the west limb of the Sun; the CME had a plane‐of‐sky speed of 1995 km s−1. We believe this CME originated in AR 0486, the same active region responsible for the extremely fast ICMEs that impacted the Earth on 29 and 30 October 2003. The ICME took at least 4.3 days to propagate past Ulysses and had a radial width of ∼2.1 AU. The ICME was a magnetic cloud, with a depressed proton beta of ∼0.01 and a smooth rotation of the magnetic field polar angle from 43° to −62°. In addition, Ulysses/SWOOPS also observed bidirectional electron streaming throughout the ICME, indicating that even at this distance, closed field lines threaded the entire event. In the days preceding the ICME, Ulysses observed disturbed solar wind conditions, including six shocks from 6 November to 15 November and several small ICMEs, indicating a high degree of solar activity.
S-Nitrosoglutathione Reduces Inflammation and Protects Brain against Focal Cerebral Ischemia in a Rat Model of Experimental Stroke
Authors: Khan Mushfiquddin , Sekhon Bipanjeet , Giri Shailendra , Jatana Manu , Gilg Anne G , Ayasolla Kamesh , Elango Chinnasamy , Singh Avtar K , Singh Inderjit
Published: January 2005

Preservation of endothelial functions with low-dose nitric oxide (NO) and inhibition of excessive production of NO from inducible NO synthase (iNOS) is a potential therapeutic approach for acute stroke. Based on this hypothesis, an NO modulator, S-nitrosoglutathione (GSNO) was used, which provided neuroprotection in a rat model of focal cerebral ischemia. Administration of GSNO after the onset of ischemia reduced infarction and improved cerebral blood flow. To understand the mechanism of protection, the involvement of inflammation in ischemic brain injury was examined. Treatment with GSNO reduced the expression of tumor necrosis factor- α, interleukin-1 β, and iNOS; inhibited the activation of microglia/macrophage (ED1, CD11-b); and downregulated the expression of leukocyte function-associated antigen-1 and intercellular adhesion molecule-1 in the ischemic brain. The number of apoptotic cells (including neurons) and the activity of caspase-3 were also decreased after GSNO treatment. Further, the antiinflammatory effect of GSNO on expression of iNOS and activation of NF- κB machinery in rat primary astrocytes and in the murine microglial cell line BV2 was tested. Cytokine-mediated expression of iNOS and activation of NF- κB were inhibited by GSNO treatment. That GSNO protects the brain against ischemia/reperfusion injury by modulating NO systems, resulting in a reduction in inflammation and neuronal cell death was documented by the results.
Nicotine Exposure, Mimicked Smoking, Directly and Indirectly Enhanced Protein Kinase C Activity in Isolated Canine Basilar Artery, Resulting in Enhancement of Arterial Contraction
Authors: Koide Masayo , Nishizawa Shigeru , Yamamoto Seiji , Yamaguchi Mitsuo , Namba Hiroki , Terakawa Susumu
Published: January 2005

Cigarette smoking is a significant risk factor in the incidence of cerebrovascular disorders. Among the many compounds in cigarette smoke, nicotine is considered to most significantly affect cerebral arterial tone. The purpose of this study is to investigate precise pharmacological effects of nicotine on the regulation of cerebral arterial tone. To mimic smoking, a low concentration of nicotine (10−6 mol/L), which is equivalent to the serum level of habitual smokers, was treated for 1 hour in an isometric tension study and for 24 hours in a study using cultured vascular endothelial cells (VECs). Using the canine basilar artery, the effect of nicotine on uridine 5′-triphosphate (UTP)-induced vasoconstriction was examined in the isometric tension study. Protein kinase C (PKC) activity in the canine basilar artery was measured by enzyme immunoassay. Endothelial function was assessed by endothelium-dependent vasodilatation and endogenous nitric oxide (NO) synthesis in VECs using a fluorescent indicator, diaminofluorescein-FM diacetate (DAF-FM/DA). Nicotine significantly enhanced UTP-induced contraction and PKC activity in the artery, and attenuated endothelium-dependent vasodilatation and NO synthesis in VECs. Because PKC activity was increased by de-endothelialization itself, endothelial dysfunction by nicotine enhances PKC activity. Because PKC was further activated by nicotine even in the de-endothelialized artery, nicotine directly affects PKC activities in smooth muscle. These results indicate that nicotine potentiates contractile response through direct and indirect PKC activation in the canine basilar artery.
CREB-Mediated Bcl-2 Protein Expression after Ischemic Preconditioning
Authors: Meller Robert , Minami Manabu , Cameron Jennifer A , Impey Soren , Chen Dexi , Lan Jing-Quan , Henshall David C , Simon Roger P
Published: January 2005

Bcl-2 plays a pivotal role in the control of cell death and is upregulated by ischemic tolerance. Because Bcl-2 expression is regulated by the transcription factor cyclic AMP response element-binding protein (CREB), we investigated the role of CREB activation in two models of ischemic preconditioning: focal ischemic tolerance after middle cerebral artery occlusion (MCAO) and in vitro ischemic tolerance modeled by oxygen–glucose deprivation (OGD). After preconditioning ischemia (30 minutes MCAO or 30 minutes OGD), phosphorylation of CREB was increased, and there was an increased interaction between the bcl-2 cyclic AMP-responsive element (CRE) promoter and nuclear proteins after preconditioning ischemia in vivo and in vitro. Chromatin immunoprecipitation revealed an increased interaction between CREB-binding protein and the bcl-2 CRE rather than CREB, after preconditioning ischemia. Ischemic tolerance was blocked by a CRE decoy oligonucleotide, which also blocked Bcl-2 expression. The protein kinase A inhibitor H89, the calcium/calmodulin kinase inhibitor KN62, and the MEK inhibitor U0126 blocked ischemic tolerance, but not the phosphatidylinositol 3-kinase inhibitor LY294002. H89, KN62, and U0126 reduced CREB activation and Bcl-2 expression. Taken together, these data suggest that after ischemic preconditioning CREB activation regulates the expression of the prosurvival protein Bcl-2.
Detrimental Effects of 17β-Oestradiol after Permanent Middle Cerebral Artery Occlusion
Authors: Bingham Deborah , Macrae I Mhairi , Carswell Hilary V
Published: January 2005

Oestrogen is a complex hormone whose role as a neuroprotectant in experimental stroke has been published in numerous studies. However, although some clinical studies report a reduction in stroke incidence by oestrogen replacement therapy in postmenopausal women, others have found increased mortality and morbidity after stroke. Diathermy occlusion of the proximal middle cerebral artery (MCAO), one of the most reproducible rodent stroke models, has consequently been employed to investigate physiologic and supraphysiologic doses of 17β-oestradiol on ischaemic brain damage. Lister Hooded rats were ovariectomised (OVX) and a 21-day release pellet (placebo, 0.025 or 0.25 mg 17β-oestradiol) implanted in the neck. At 2 weeks after OVX, animals underwent MCAO and were perfusion fixed 24 hours later. Neuronal perikaryal damage was assessed from haematoxylin and eosin-stained sections and in adjacent sections, axonal pathology was assessed with amyloid precursor protein and Neurofilament 200 (NF-200) immunohistochemistry. 17β-Oestradiol induced a dose-dependent increase in neuronal perikaryal damage, 0.025 and 0.25 mg 17β-oestradiol increased damage by 20% ( P<0.05) and 27.5% ( P<0.01) compared with placebo. 17β-Oestradiol did not influence axonal pathology compared with placebo. Our results suggest that 17β-oestradiol treatment can exacerbate brain damage in experimental stroke. Thus, further investigation into the role of oestrogen and the mechanisms which mediate its effects in stroke is required.
β2‐Adrenergic Receptor Gene Variations Associated with Stage‐2 Hypertension in Northern Han Chinese
Authors: Ge D. , Huang J. , He J. , Li B. , Duan X. , Chen R. , Gu D.
Published: January 2005

The aim of this study was to investigate the association between polymorphisms in the β2‐adrenergic receptor gene (ADRB2) (−47C/T, Arg16/Gly, Gln27/Glu) and stage‐2 hypertension in northern Han Chinese. We recruited 503 individuals with stage‐2 hypertension and 504 age‐, gender‐, and area‐matched controls from the International Collaborative Study of Cardiovascular Disease in Asia. Genotyping was performed using PCR‐RFLP. Logistic regression analyses revealed that carriers of the Gly16 allele had a significantly higher odds ratio (OR) for hypertension, while carriers of the Glu27 allele had a significantly lower OR. In multivariate linear regression analyses, the Arg16/Gly and Gln27/Glu genotypes were significantly associated with systolic blood pressure level (p= 0.004 and p < 0.001, respectively). In haplotype analyses, we found the frequency of haplotypes composed of the Gly16 and Gln27 alleles was significantly higher, whereas the frequency of haplotypes composed of the Arg16 and Glu27 alleles was significantly lower, in hypertensives compared to their controls (both p= 0.001). These results indicate that the Gly16 and Gln27 alleles of the ADRB2 gene confer an increased risk for stage‐2 hypertension in this northern Han Chinese population.
Double Heterozygosity with Mutations Involving both the GJB2 and GJB6 Genes is a Possible, but very Rare, Cause of Congenital Deafness in the Czech Population
Authors: Seeman P. , Bendová O. , Rašková D. , Malíková M. , Groh D. , Kabelka Z.
Published: January 2005

Mutations in the GJB2 gene are the most common cause of prelingual, autosomal recessive, sensorineural hearing loss worldwide. Nevertheless, 10% to 50% of patients with prelingual nonsyndromic deafness only carry one mutation in the GJB2 gene. Recently a large 342 kb deletion named Δ(GJB6‐D13S1830) involving the GJB6 gene was reported in Spanish and French deafness patients, either in a homozygous state or in combination with a monoallelic GJB2 mutation. No data have been reported about the frequency of this mutation in central Europe.

Thirteen Czech patients with prelingual nonsyndromic sensorineural deafness carrying only one pathogenic mutation in the GJB2 gene were tested for the presence of the Δ(GJB6‐D13S1830) mutation. One patient with a GJB2 mutation (313del14) also carried the Δ(GJB6‐D13S1830). This is the first reported Czech case, and probably also the first central European case, of prelingual deafness due to mutations involving both the GJB2 and GJB6 genes. In addition, the Δ(GJB6‐D13S1830) was not detected in 600 control chromosomes from Czech individuals with normal hearing. We show that in the Czech Republic the Δ(GJB6‐D13S1830) is not the second most common causal factor in deafness patients heterozygous for a single GJB2 mutation, and that Δ(GJB6‐D13S1830) is very rare in central Europe compared to reports from Spain, France and Israel.
Genetic Association Studies in Complex Disease: Disentangling Additional Predisposing Loci from Associated Neutral Loci Using a Constrained ‐ Permutation Approach
Authors: Spijker G.T. , Nolte I.M. , Jansen R.C. , Te Meerman G.J.
Published: January 2005

In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi‐allelic loci only. We wanted to develop a method that is more suited for multi‐allelic loci, such as microsatellite markers.We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA‐region. The method showed the expected number of false‐positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.
Phenotype Severity and Genetic Variation at the Disease Locus: An Investigation of Nail Dysplasia in the Nail Patella Syndrome
Authors: Dunston J. A. , Lin S. , Park J. W. , Malbroux M. , McIntosh I.
Published: January 2005

The genetic bases underlying the range and severity of phenotypes in Mendelian disorders is poorly understood; however, improvements in this area have the potential to facilitate analysis of oligogenic disorders. The nail dysplasia observed in Nail Patella Syndrome (NPS) was selected as a quantifiable variable within a Mendelian disorder, for which data could be readily obtained, to allow investigation of the genetic basis of variation. Analysis of SNP haplotypes across the LMX1B gene demonstrated association between the haplotype of the mutant allele and the variability in the nail score (p = 0.024). These results are in contrast to those obtained previously, which supported a modifying role for the wild‐type allele. Since there is no evidence that particular mutations, or classes of mutation, are associated with the variation (p > 0.5), further work is required to identify the elements associated with the LMX1B gene that mediate phenotypic severity.
The use of Allelic Expression Differences to Ascertain Functional Polymorphisms Acting in cis: Analysis of MMP1 Transcripts in Normal Lung Tissue
Authors: Heighway J. , Bowers N. L. , Smith S. , Betticher D. C. , Santibáñez Koref M. F.
Published: January 2005

Aberrant expression of matrix metalloproteinase 1 (MMP1) has been implicated in a number of pathological conditions of the lung. In vitro results and analysis of tumours and cell lines suggest that an insertion/deletion polymorphism at position ‐1607 in the promoter of the gene can influence expression levels. However, whether this polymorphism is associated with differences in expression in normal lung tissue remains to be established. Polymorphisms affecting expression in cis will lead to alleles with different expression levels and will result in unequal expression of both alleles in heterozygous individuals (allelic expression imbalance, AEI). This can be detected using a transcribed marker. Here we follow a new approach and use AEI to ascertain that the ‐1607 polymorphism is associated with allelic expression differences of MMP1 in normal lung tissue. This approach could be used to map the sites associated with inter‐individual expression differences in other genes. This is of particular interest since such sites allow prediction of expression levels, and can be used to test whether genetically determined differences in expression influence inter‐individual differences of a phenotype of interest, such as disease predisposition.
Fine Mapping Functional Sites or Regions from Case‐Control Data Using Haplotypes of Multiple Linked SNPs
Authors: Cheng Rong , Ma Jennie Z. , Elston Robert C. , Li Ming D.
Published: January 2005

Previously, we reported an algorithm for scanning a large number of tightly linked single nucleotide polymorphisms (SNPs) for LD mapping of functional sites or regions from a family‐based association design. In the present study, we extend our method to a case‐control design. We first use the expectation maximization (EM) algorithm to estimate haplotype frequencies of multiple linked SNPs, and follow this by constructing a contingency table statisticSfor LD analysis, based on the estimated haplotype frequencies. An empiricalp‐value is obtained based on the null distribution of the maximum ofS(S *) from a large number (e.g., 1,000 or more) of randomized permutations. The proposed algorithm has been implemented in a computer program in which window searching for functional SNP sites can cover any number of loci without limitation, except that of computer storage. Unlike other programs for a case‐control design that always conduct tests at a fix window width, in our program after setting a maximum size of haplotype window width, for a given maximum window width all possible widths of haplotypes are utilized to find the maximum statisticS * for each locus under investigation. The sensitivity of the proposed algorithm has been examined with simulated and real genotyping datasets. Association analyses indicate that our program is powerful enough to detect most, if not all, functional SNPs simulated in the original model or identified in the original report. Moreover, the program is very flexible and can be used in either regional or genome‐wide scanning for association analysis with SNP markers.
Prototypes and strategy: assigning causal credit using fuzzy sets
Authors: Kogut Bruce , MacDuffie John Paul , Ragin Charles
Published: January 2005

Abstract Strategies often are stylized on the basis of particular prototypes (e.g. differentiate or low cost) whose efficacy is uncertain often due to uncertainty of complex interactions among its elements. Because of the difficulty in assigning causal credit to a given element for an outcome, the adoption of better practices that constitute strategies is frequently characterized as lacking in causal validity. We apply Ragin's (2000) fuzzy logic methodology to identify high performance configurations in the 1989 data set of MacDuffie (1995). The results indicate that discrete prototypes of practices are associated with higher performance, but that the variety of outcomes points to experimentation and search. These results reflect the fundamental challenge of complex causality when there is limited diversity in observed experiments given the large number of choice variables. Fuzzy set methodology provides an approach to reduce this complexity by logical rules that permit an exploration of the simplifying assumptions. It is this interaction between prototypical understandings of strategy and exploration in the absence of data that is the most important contribution of this methodology.
Multireference configuration interaction calculations for positronium halides
Authors: Saito Shiro L.
Published: January 2005

Multireference configuration interaction (MRCI) calculations of the positronium halides, PsF, PsCl, PsBr, and PsI, are carried out, to give positron ionization energies, positronium binding energies, and two-photon annihilation rates. All CI calculations consider only valence correlation effect with a frozen-core approximation, and use the orbitals with angular momentum up to 8. To incorporate the effects of many-body correlations in the energies and two-photon annihilation rates, the MRCI calculations are repeated with increasing reference configurations, and the full CI limits of these energies and annihilation rates are estimated. The contribution from orbitals having angular momentum greater than 8 to those values is also estimated. Relative to our previous single reference CI calculations, many-body correlation effects significantly increase the positron ionization energies, positronium binding energies, and two-photon annihilation rates. The structures of the positronium halides are also discussed.
Continuous grey scale image printing on the liquid crystal cell
Authors: Yamaguchi Rumiko , Sato Susumu
Published: January 2005

The continuous grey scale image is printed on the liquid crystal (LC) cell through the similar printing process on a photographic paper. The LC cell is prepared with a rubbed photo-cross-linkable polymer coated substrate whose azimuthal anchoring strength increases by exposing the unpolarized UV light. The cell filled with the LC is exposed to the UV light through a negative film, and is thermally developed and fixed. The twist angle continuously changes from 0° to about 90° by increasing the exposure, and the positive image with continuous grey levels appears in the LC cell between parallel polarizers.
Fast birefringent mode stressed liquid crystal
Authors: West John L. , Zhang Guoqiang , Glushchenko Anatoliy , Reznikov Yurii
Published: January 2005

We report a stressed liquid crystal (SLC) that produce a large shift in phase retardation at submillisecond speeds. The SLC consists of uniformly aligned micro-domains of a liquid crystal dispersed in a polymer structure. Mechanical stress produces uniform alignment, essentially eliminates light scattering, and substantially improves the electro-optic performance. A 22-μm-thick SLC film switches more than 2μm of phase retardation in less than 1ms. The system has a linear voltage response with essentially no hysteresis.
Passivation effect of Al∕LiF electrode on C60 diodes
Authors: Huang C. J. , Grozea D. , Turak A. , Lu Z. H.
Published: January 2005

The current–voltage characteristics, the temperature dependence of the dark conductivity, and the effect of oxygen exposure of C60 sandwich diodes are compared with Al and Al∕LiF as electrodes. It appears that a thin LiF interlayer can help to preserve the space-charge limited conduction in C60 diodes under exposure to air, by considerably suppressing the oxygen diffusion into the C60 film and reaction at the Al∕C60 interface.
Optical properties of InAs∕GaAs surface quantum dots
Authors: Miao Z. L. , Zhang Y. W. , Chua S. J. , Chye Y. H. , Chen P. , Tripathy S.
Published: January 2005

We report long-wavelength photoluminescence emission (∼1.6–1.7μm) from self-organized InAs surface quantum dots (SQDs) grown on GaAs substrate without any capping layers. Photoluminescence (PL) properties of these quantum dots (QDs) are strongly affected by the surface states and strain relaxation mechanism. Compared to the case of capped InAs QDs, a large redshift of about 466nm observed in the PL spectrum of SQDs can be attributed to the strain relaxation and the strong coupling of the confined states with the surface states. The PL properties of these SQDs can also be influenced by the presence of quasi-infinite surface potential.
Phosphodiesterase 4D is required for β
2
adrenoceptor subtype-specific signaling in cardiac myocytes
Authors: Xiang Yang , Naro Fabio , Zoudilova Maria , Jin S.-L. Catherine , Conti Marco , Kobilka Brian
Published: January 2005

β adrenoceptor (βAR) signaling is finely regulated to mediate the sympathetic nervous system control of cardiovascular function. In neonatal cardiac myocytes, β
1
AR activates the conventional G
s
/cAMP pathway, whereas β
2
AR sequentially activates both the G
s
and G
i
pathways to regulate the myocyte contraction rate. Here, we show that phosphodiesterase 4D (PDE4D) selectively impacts signaling by β
2
AR in neonatal cardiac myocytes, while having little or no effect on β
1
AR signaling. Although β
2
AR activation leads to an increase in cAMP production, the cAMP generated does not have access to the protein kinase A-dependent signaling pathways by which the β
1
AR regulates the contraction rate. However, this restricted access is lost in the presence of PDE4 inhibitors or after ablation of PDE4D. These results not only suggest that PDE4D is an integral component of the β
2
AR signaling complex, but also underscore the critical role of subcellular cAMP regulation in the complex control of receptor signaling. They also illustrate a mechanism for fine-tuned βAR subtype signaling specificity and intensity in the cardiac system.
Different GABA
A
receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates
Authors: Rowlett James K. , Platt Donna M. , Lelas Snjezana , Atack John R. , Dawson Gerard R.
Published: January 2005

Benzodiazepines exert their effects by binding to multiple subtypes of the GABA
A
receptor, the predominant subtypes in the brain being those that contain α
1
-, α
2
-, α
3
-, and α
5
-subunits. To understand the potentially different roles of these subtypes in the therapeutic and side effects of benzodiazepines, we evaluated GABA
A
receptor subtype-preferring compounds in nonhuman primate models predictive of anxiolytic, sedative, motor, subjective, and reinforcing effects of benzodiazepine-type drugs. These compounds included zolpidem, which shows preferential binding to GABA
A
receptors containing α
1
-subunits (α
1
GABA
A
receptors); L-838,417, which shows functional selectivity for α
2
GABA
A
, α
3
GABA
A
, and α
5
GABA
A
receptors; and nonselective conventional benzodiazepines. The results provide evidence in nonhuman primates that α
1
GABA
A
receptors do not play a key role in the anxiolytic and muscle-relaxant properties of benzodiazepine-type drugs; instead, these effects involve α
2
GABA
A
, α
3
GABA
A
, and/or α
5
GABA
A
subtypes. Our results also suggest that the α
1
GABA
A
receptor subtype might be critically involved in the subjective, sedative, and motor effects of benzodiazepine-type drugs. In contrast, stimulation of α
1
GABA
A
receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs.
Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants
Authors: Di Giacomo Monica , Barchi Marco , Baudat Frédéric , Edelmann Winfried , Keeney Scott , Jasin Maria
Published: January 2005

Defects in meiotic recombination in many organisms result in arrest because of activation of a meiotic checkpoint(s). The proximal defect that triggers this checkpoint in mammalian germ cells is not understood, but it has been suggested to involve either the presence of DNA damage in the form of unrepaired recombination intermediates or defects in homologous chromosome pairing and synapsis independent of DNA damage
per se
. To distinguish between these possibilities in the female germ line, we compared mouse oocyte development in a mutant that fails to form the double-strand breaks (DSBs) that initiate meiotic recombination (
Spo11
-/-
) to mutants with defects in processing DSBs when they are formed (
Dmc1
-/-
and
Msh5
-/-
), and we examined the epistasis relationships between these mutations. Absence of DSB formation caused a partial defect in follicle formation, whereas defects in DSB repair caused earlier and more severe meiotic arrest, which could be suppressed by eliminating DSB formation. Therefore, our analysis reveals that there are both DNA-damage-dependent and -independent responses to recombination errors in mammalian oocytes. By using these findings as a paradigm, we also examined oocyte loss in mutants lacking the DNA-damage checkpoint kinase ATM. The absence of ATM caused defects in folliculogenesis that were similar to those in
Dmc1
mutants and that could be suppressed by
Spo11
mutation, implying that oocyte death in
Atm
-deficient animals is a response to defective DSB repair.
Positive charge is an important feature of the C-terminal transport signal of the VirB/D4-translocated proteins of
Agrobacterium
Authors: Vergunst Annette C. , van Lier Miranda C. M. , den Dulk-Ras Amke , Grosse Stüve Thomas A. , Ouwehand Anette , Hooykaas Paul J. J.
Published: January 2005

Several human pathogens and the plant pathogen
Agrobacterium tumefaciens
use a type IV secretion system for translocation of effector proteins into host cells. How effector proteins are selected for transport is unknown, but a C-terminal transport signal is present in the proteins translocated by the
A. tumefaciens
VirB/D4 type IV secretion system. We characterized this signal in the virulence protein VirF by alanine scanning and further site-directed mutagenesis. The Cre recombinase was used as a reporter to measure the translocation efficiency of Cre-Vir fusions from
A. tumefaciens
to
Arabidopsis
. The data unambiguously showed that positive charge is an essential characteristic of the C-terminal transport signal. We increased the sensitivity of this translocation assay by modifying the Cre-induced readout in host cells from kanamycin resistance to GFP expression. This improvement allowed us to detect translocation of the VirD2 relaxase protein in the absence of transferred DNA, showing that attachment to the transferred DNA is not essential for transport by the VirB/D4 system. We also found another translocated effector protein, namely the VirD5 protein encoded by the tumor-inducing plasmid. According to secondary structure predictions, the C termini of all VirB/D4-translocated proteins identified so far are unstructured; however, they contain a characteristic hydropathic profile. Based on sequence alignments and mutational analysis of VirF, we conclude that the C-terminal transport signal for recruitment and translocation of effector proteins by the
A. tumefaciens
VirB/D4 system is hydrophilic and has a net positive charge with a consensus motif of R-X(7)-R-X-R-X-R-X-X(n)>.
Zinc fingers as protein recognition motifs: Structural basis for the GATA-1/Friend of GATA interaction
Authors: Liew Chu Kong , Simpson Raina J. Y. , Kwan Ann H. Y. , Crofts Linda A. , Loughlin Fionna E. , Matthews Jacqueline M. , Crossley Merlin , Mackay Joel P.
Published: January 2005

GATA-1 and friend of GATA (FOG) are zinc-finger transcription factors that physically interact to play essential roles in erythroid and megakaryocytic development. Several naturally occurring mutations in the
GATA-1
gene that alter the FOG-binding domain have been reported. The mutations are associated with familial anemias and thrombocytopenias of differing severity. To elucidate the molecular basis for the GATA-1/FOG interaction, we have determined the three-dimensional structure of a complex comprising the interaction domains of these proteins. The structure reveals how zinc fingers can act as protein recognition motifs. Details of the architecture of the contact domains and their physical properties provide a molecular explanation for how the
GATA-1
mutations contribute to distinct but related genetic diseases.
The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development
Authors: Ren Jinyu , Shi Mingan , Liu Renshui , Yang Qi-Heng , Johnson Teri , Skarnes William C. , Du Chunying
Published: January 2005

Baculoviral inhibitor of apoptosis repeat-containing (Birc)6 gene/BIRC6 (Bruce/APOLLON) encodes an inhibitor of apoptosis and a chimeric E2/E3 ubiquitin ligase in mammals. The physiological role of Bruce in antiapoptosis is unknown. Here, we show that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality. This apoptosis is associated with up-regulation and nuclear localization of the tumor suppressor p53 and activation of mitochondrial apoptosis, which includes up-regulation of Bax, Bak, and Pidd, translocation of Bax and caspase-2 onto mitochondria, release of cytochrome
c
and apoptosis-inducing factor, and activation of caspase-9 and caspase-3. Mutant mouse embryonic fibroblasts are sensitive to multiple mitochondrial death stimuli but resistant to TNF. In addition, eliminating p53 by RNA interference rescues cell viability induced by Bruce ablation in human cell line H460. This viability preservation results from reduced expression of proapoptotic factors Bax, Bak, and Pidd and from prevention of activation of caspase-2, -9, and -3. The amount of second mitochondrial-derived activator of caspase and Omi does not change. We conclude that p53 is a downstream effector of Bruce, and, in response to loss of Bruce function, p53 activates Pidd/caspase-2 and Bax/Bak, leading to mitochondrial apoptosis.
Protein conformational space in higher order ϕ-Ψ maps
Authors: Sims Gregory E. , Choi In-Geol , Kim Sung-Hou
Published: January 2005

We have mapped protein conformational space from two to seven residue lengths by employing multidimensional scaling on a data matrix composed of pair-wise angular distances for multiple ϕ-Ψ values collected from high-resolution protein structures. The resulting global maps show clustering of peptide conformations that reveals a dramatic reduction of conformational space as sampled by experimentally observed peptides. Each map can be viewed as a higher order ϕ-Ψ plot defining regions of space that are conformationally allowed.
Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells
Authors: Shao Matt X. G. , Nadel Jay A.
Published: January 2005

Mucus hypersecretion is a prominent manifestation in patients with chronic inflammatory airway diseases. MUC5AC mucin is a major component of airway mucus, and its expression is modulated by a TNF-α-converting enzyme (TACE)–EGF receptor pathway that can be activated by reactive oxygen species (ROS). Dual oxidase 1 (Duox1), a homologue of glycoprotein p91
phox
, is expressed in airway epithelium and generates ROS. We hypothesize that Duox1 activates TACE, cleaving pro-TGF-α into soluble TGF-α, resulting in mucin expression. To examine this hypothesis, we stimulated both normal human bronchial epithelial cells and NCI-H292 airway epithelial cells with phorbol 12-myristate 13-acetate and with human neutrophil elastase. These stimuli induced TACE activation, TGF-α release, and mucin expression, effects that were inhibited by ROS scavengers, implicating ROS in TACE activation. Inhibition of epithelial NADPH oxidase or knockdown of Duox1 expression with small interfering RNA prevented ROS generation, TGF-α release, and mucin expression by these stimuli, implicating Duox1 in TACE activation and mucin expression. Furthermore, the PKCδ/PKCθ inhibitor rottlerin prevented the effects induced by phorbol 12-myristate 13-acetate and human neutrophil elastase, suggesting that PKCδ and PKCθ are involved in Duox1 activation. From these results, we conclude that Duox1 plays a critical role in mucin expression by airway epithelial cells through PKCδ/PKCθ-Duox1-ROS-TACE-pro-ligand-EGF receptor cascade.
Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility
Authors: Clarke Paul , Ghani Azra C
Published: January 2005

The incidence of variant Creutzfeldt–Jakob disease (vCJD) in the United Kingdom appears to be in decline, with only four deaths reported this year (to 6 September 2004). However, results of a survey of lymphoreticular tissues have suggested a substantially higher prevalence of vCJD than expected from the clinical data alone. There are two plausible explanations for this discrepancy: first, a proportion of those infected will not develop clinical disease (subclinical infection); and second, the genetic group in which no clinical cases of vCJD have yet occurred is susceptible. Using mathematical models for the primary transmission of bovine spongiform encephalopathy to humans, we explore the impact of these hypotheses on case predictions. Under the first hypothesis, the results suggest relatively few future cases will arise via primary transmission, but that these cases are a small proportion of those infected, with most having subclinical infection. Under the second hypothesis, results suggest a maximum fivefold increase in cases, but this hypothesis is unable to account for the discrepancy between clinical cases and the estimated prevalence. Predictions of future cases of vCJD therefore remain uncertain, particularly given the recent identification of additional cases infected via blood transfusion.
Relationships between the Royal Society and the Académie des Sciences in the late eighteenth century
Authors: Crosland M.
Published: January 2005

Harmonious relations and scientific exchange between Britain and France in the eighteenth century were undermined by a succession of wars. Nevertheless, The Royal Society and the Paris Academy of Sciences succeeded in a fairly consistent exchange of scientific news and publications, with intermittent visits by scientists. Joseph Banks PRS claimed that the sciences were never at war. Election to honorary membership of the other society also helped strengthen relationships. A proposal for cooperation in the reform of weights and measures was halted in 1791 by political events in France.
A Roman correspondence: George Ent and Cassiano dal Pozzo, 1637–55
Authors: Cook A.
Published: January 2005

George Ent (FRS 1663), a distinguished physician, was in Rome in 1636, visited the notable collector Cassiano dal Pozzo and saw his Paper Museum. After he returned to London he carried on a correspondence with Cassiano in letters of more than ordinary interest. Cassiano had sent Ent specimens of fossil wood and a table made from fossil wood. They had come from the estates at Acquasparta belonging to Prince Federico Cesi, the founder of the Accademia dei Lincei. The specimens and the table were shown to early meetings of The Royal Society and had a significant part in the developing debate on the origin of fossils. The letters also record exchanges of books between London and Rome. Among medical matters there is news of William Harvey and his works.
Unusual quantum states: non–locality, entropy, Maxwell's demon and fractals
Authors: Bender Carl M. , Brody Dorje C. , Meister Bernhard J.
Published: January 2005

This paper analyses the mathematical properties of some unusual quantum states
that are constructed by inserting an impenetrable barrier into a chamber confining
a single particle. If the barrier is inserted at a fixed node of the wave function, then
the energy of the system is unchanged. After barrier insertion, a measurement is
made on one side of the chamber to determine if the particle is physically present.
The measurement causes the wave function to collapse, and the energy contained
in the subchamber where the particle is not present transfers instantaneously to the
other subchamber where the particle now exists. This thought experiment constitutes
an elementary example of an Einstein–Podolsky–Rosen experiment based on energy
conservation rather than momentum or angular–momentum conservation. A more
interesting situation arises when one inserts the barrier at a point that is not a fixed
node of the wave function because this process changes the energy of the system; the
faster the barrier is inserted, the greater the change in the energy. At the point of a
sudden insertion the energy density becomes infinite; this energy instantly propagates
across the subchamber and causes the wave function to become fractal. If an energy
measurement is carried out on such a fractal wave function, the resulting mixed
state has finite non–zero entropy. Fractal mixed states having unbounded entropy
are also constructed and their properties are discussed. For a finite time insertion of
the barrier, Landauer's principle is shown to be insufficient to resolve the apparent
violation of the second law of thermodynamics that arises when a Maxwell demon
is present. This problem is resolved by calculating the energy required to insert the
barrier.