bluuebunny/crossref_metadata_2025 huggingface dataset:
The development of a joule level of XeF(C-A) laser by optical
pumping
Authors: YU LI , LIU JING-RU , MA LIAN-YING , YI AI-PING , HUANG CHAO , AN XIAO-XIA , ZHANG YONG-SHENG , SU JIAN-CANG , ZENG ZHENG-ZHONG
Published: December 2005

A joule level of XeF(C-A) laser optically pumped by a sectioned
surface discharge was developed. The irradiative intensity of pumping
source was diagnosed by calculating XeF2 photo-dissociation
wave evolvement which was photographed by a framing camera. The photon
flux in the wavelength region of 140 to 170nm is about 5 ×
1023 photon s−1cm−2, that
corresponds to the irradiative brightness temperature of more than 25000
K. The laser experiments were carried out in different conditions. The
maximum laser output energy of 2.5 J was obtained with the total
conversion efficiency of 0.1%.
Free standing target technologies for inertial fusion energy: Target
fabrication, characterization, and delivery
Authors: KORESHEVA E.R. , OSIPOV I.E. , ALEKSANDROVA I.V.
Published: December 2005

Inertial fusion energy (IFE) research indicates that the energy
generation by means of cryogenic fuel target compression requires that
targets must be injected to the target chamber center at a rate of about 6
Hz. This requirement can be fulfilled only if the targets are
free-standing. The most interesting results concerning the activity of the
Lebedev Physical Institute in the area of free-standing targets (FST)
fabrication, characterization and delivery are presented.
Characteristics of pulsed power generator by versatile inductive
voltage adder
Authors: YATSUI KIYOSHI , SHIMIYA KOUICHI , MASUGATA KATSUMI , SHIGETA MASAO , SHIBATA KAZUHIKO
Published: December 2005

A pulsed power generator by inductive voltage adder, versatile
inductive voltage adder (VIVA-I), which features a high average potential
gradient (2.5 MV/m), was designed and is currently in operation,. It
was designed to produce an output pulse of 4 MV/60 ns by adding 2 MV
pulses in two-stages of induction cells, where amorphous cores are
installed. As a pulse forming line, we used a Blumlein line with the
switching reversed, where cores are automatically biased due to the
presence of prepulse. Good reproducibility was obtained even in the
absence of the reset pulse. Within ∼40% of full charge voltage, pulsed
power characteristics of Marx generator, pulse forming line (PFL),
transmission line (TL), and induction cells were tested for three types of
loads; open-circuit, dummy load of liquid (CuSO4) resistor, and
electron beam diode. In the open-circuit test, ∼2.0 MV of output
voltage was obtained with good reproducibility. Dependences of output
voltage on diode impedances were evaluated by using various dummy loads,
and the results were found as expected. An electron-beam diode was
operated successfully, and ∼18 kA of beam current was obtained at the
diode voltage of ∼1 MV.
An architectural framework for modeling teleoperated service robots
Authors: Álvarez Bárbara , Sánchez-Palma Pedro , Pastor Juan A. , Ortiz Francisco
Published: December 2005

Teleoperated robots are used to perform tasks that human operators cannot carry out because of the nature of the tasks themselves or the hostile nature of the working environment. Though many control architectures have been defined for developing these kinds of systems reusing common components, none has attained all its objectives because of the high variability of system behaviors. This paper presents a new architectural approach that takes into account the latest advances in robotic architectures while adopting a component-oriented approach. This approach provides a common framework for developing robotized systems with very different behaviors and for integrating intelligent components. The architecture is currently being used, tested and improved in the development of a family of teleoperated robots which perform cleaning of ship-hull surfaces.
Sensor design and signal processing for an advanced sonar ring
Authors: Fazli Saeid , Kleeman Lindsay
Published: December 2005

A conventional sonar ring measures the range to objects based on the first echo and is widely used in indoor mobile robots. In contrast, advanced sonar sensing can produce accurate range and bearing (incidence angle) measurements to multiple targets using multiple receivers and multiple echoes per each receiver at the expense of intensive computation. This paper presents an advanced sonar ring that employs a low receiver sample rate to achieve processing of 48 receiver channels at near real time repetition rates of 11.5 Hz. The sonar ring sensing covers 360 degrees around the robot for specular targets for ranges up to six metres, with simultaneously firing of all its 24 transmitters. Digital Signal Processing (DSP) techniques and interference rejection ideas are applied in this sensor to produce a fast and accurate sonar ring. Seven custom designed DSP boards process the receivers sampled at 250 kHz to maximize the speed of processing and to limit memory requirements. This paper presents the new sensor design, the hardware structure, the software architecture, and signal processing of the advanced sonar ring. Repeatability and accuracy of the measurements are tested to characterize the proposed sensor. Due to the low sample rate of 250 kHz, a problem called cycle hopping can occur. The paper presents a solution to cycle hopping and a new transmit coding based on pulse duration to differentiate neighbouring transmitters in the ring. Experimental data show the effectiveness of the designed sensor in indoor environments.
Modelling of repeatability phenomena using the stochastic ellipsoid approach
Authors: Brethé Jean-François , Vasselin Eric , Lefebvre Dimitri , Dakyo Brayima
Published: December 2005

A stochastic ellipsoid modelling of repeatability is proposed for industrial manipulator robots. The covariance matrix of angular position is determined introducing the jump process, which reveals to be a first and second order stationary Gaussian process.

From this accurate covariance matrix, the stochastic ellipsoid theory gives the density of position in the workspace around the mean position. Hence the pose repeatability index can be computed in different locations. Computed and experimental repeatability are compared. Experimental repeatability variability is studied. A new “intrinsic repeatability index” is proposed. In conclusion, the modelling reflects well the location and load influence on the repeatability.
‘Stop kissing and steaming!’: tuberculosis and the occupational health movement in Massachusetts and Lancashire, 1870–1918
Authors: GREENLEES JANET
Published: December 2005

Historians have argued that American social welfare reformers looked to Europe for examples of successful programmes. This article provides a counter-case where a progressive American state, Massachusetts, developed public health reforms prior to their British counterparts. Social concerns about reducing cases of tuberculosis in Massachusetts' cotton manufacturing cities led to the transference of the public health discourse from the urban living environment to the workplace. This same relationship could have been applied within the Lancashire industry. Instead, the urban public health discourse focused on living conditions. In both countries, local and state political structures influenced health campaigners' actions.
‘The finest municipal hospital service in the world’?: contemporary perceptions of the London County Council's hospital provision, 1929–39
Authors: STEWART JOHN
Published: December 2005

This article first explains why the London County Council (LCC) was, by the 1930s, the largest provider of hospital beds in Britain. It then examines contemporary perceptions of the LCC hospital service showing how the complex series of responses to it fed into debates about the nature of the post-war National Health Service. Finally, an assessment is made of the service's place in the history of the health services.
The suburban high flat in the post-war reconstruction of Birmingham, 1945–71
Authors: JONES PHIL
Published: December 2005

Between 1950 and 1971 Birmingham City Council built 464 housing blocks of five or more storeys. The city pursued parallel programmes of building high-rise flats both in the central areas on slum cleared land and in its suburbs on greenfield sites. Examining Birmingham's post-war suburban housing programme, this article suggests that the use of high-rise in suburban areas represented an important change in the nature of British cities, both in the use of a particular building type on the urban fringe and also in the location of high-density workers' housing far outside of the city core.
A weighted finite state transducer translation template model for statistical machine translation
Authors: KUMAR SHANKAR , DENG YONGGANG , BYRNE WILLIAM
Published: December 2005

We present a Weighted Finite State Transducer Translation Template Model for statistical machine translation. This is a source-channel model of translation inspired by the Alignment Template translation model. The model attempts to overcome the deficiencies of word-to-word translation models by considering phrases rather than words as units of translation. The approach we describe allows us to implement each constituent distribution of the model as a weighted finite state transducer or acceptor. We show that bitext word alignment and translation under the model can be performed with standard finite state machine operations involving these transducers. One of the benefits of using this framework is that it avoids the need to develop specialized search procedures, even for the generation of lattices or N-Best lists of bitext word alignments and translation hypotheses. We report and analyze bitext word alignment and translation performance on the Hansards French-English task and the FBIS Chinese-English task under the Alignment Error Rate, BLEU, NIST and Word Error-Rate metrics. These experiments identify the contribution of each of the model components to different aspects of alignment and translation performance. We finally discuss translation performance with large bitext training sets on the NIST 2004 Chinese-English and Arabic-English MT tasks.
Reading comprehension tests for computer-based understanding evaluation
Authors: WELLNER BEN , FERRO LISA , GREIFF WARREN , HIRSCHMAN LYNETTE
Published: December 2005

Reading comprehension (RC) tests involve reading a short passage of text and answering a series of questions pertaining to that text. We present a methodology for evaluation of the application of modern natural language technologies to the task of responding to RC tests. Our work is based on ABCs (Abduction Based Comprehension system), an automated system for taking tests requiring short answer phrases as responses. A central goal of ABCs is to serve as a testbed for understanding the role that various linguistic components play in responding to reading comprehension questions. The heart of ABCs is an abductive inference engine that provides three key capabilities: (1) first-order logical representation of relations between entities and events in the text and rules to perform inference over such relations, (2) graceful degradation due to the inclusion of abduction in the reasoning engine, which avoids the brittleness that can be problematic in knowledge representation and reasoning systems and (3) system transparency such that the types of abductive inferences made over an entire corpus provide cues as to where the system is performing poorly and indications as to where existing knowledge is inaccurate or new knowledge is required. ABCs, with certain sub-components not yet automated, finds the correct answer phrase nearly 35 percent of the time using a strict evaluation metric and 45 percent of the time using a looser inexact metric on held out evaluation data. Performance varied for the different question types, ranging from over 50 percent on who questions to over 10 percent on what questions. We present analysis of the roles of individual components and analysis of the impact of various characteristics of the abductive proof procedure on overall system performance.
Correlations between the satellite‐derived seasonal cycles of phytoplankton biomass and aerosol optical depth in the Southern Ocean: Evidence for the influence of sea ice
Authors: Gabric Albert J. , Shephard Jill M. , Knight Jon M. , Jones Graham , Trevena Anne J.
Published: December 2005

The relationship between the production of dimethylsulfide (DMS) in the upper ocean and atmospheric sulfate aerosols has been confirmed through local shipboard measurements, and global modeling studies alike. In order to examine whether such a connection may be recoverable in the satellite record, we have analyzed the correlation between mean surface chlorophyll (CHL) and aerosol optical depth (AOD) in the Southern Ocean, where the marine atmosphere is relatively remote from anthropogenic and continental influences. We carried out the analysis in 5‐degree zonal bands between 50°S and 70°S, for the period (1997–2004), and in smaller meridional sectors in the Eastern Antarctic, Ross and Weddell seas. Seasonality is moderate to strong in both CHL and AOD signatures throughout the study regions. Coherence in the CHL and AOD time series is strong in the band between 50°S and 60°S, however this synchrony is absent in the sea‐ice zone (SIZ) south of 60°S. Marked interannual variability in CHL occurs south of 60°S, presumably related to variability in sea‐ice production during the previous winter. We find a clear latitudinal difference in the cross correlation between CHL and AOD, with the AOD peak preceding the CHL bloom by up to 6 weeks in the SIZ. This suggests that substantial trace gas emissions (aerosol precursors) are being produced over the SIZ in spring (October–December) as sea ice melts. This hypothesis is supported by field data that record extremely high levels of sulfur species in sea ice, surface seawater, and the overlying atmosphere during ice melt.
Planetary wave coupling from the stratosphere to the thermosphere during the 2002 Southern Hemisphere pre‐stratwarm period
Authors: Palo S. E. , Forbes J. M. , Zhang X. , Russell J. M. , Mertens C. J. , Mlynczak M. G. , Burns G. B. , Espy P. J. , Kawahara T. D.
Published: December 2005

Temperature observations between 20 and 120 km from the SABER instrument on the TIMED spacecraft are used to investigate the nature of planetary wave activity during the 60 days prior to the midwinter stratospheric warming that commenced on 26 September, 2002 in the Southern Hemisphere. The primary wave components consist of eastward‐propagating quasi‐10‐day waves with zonal wave numbers s = 1 and s = 2, and a stationary planetary wave with s = 1. The waves are found to extend from the lower stratosphere to the 100–120 km height region with surprisingly little amplitude attenuation, although wave amplitudes oscillate with altitude like a standing wave pattern. Time evolution of the waves is also addressed with emphasis on 86 km altitude, where temperature observations from three Antarctic stations at Davis (69°S, 78°W), Rothera (68°S, 68°W) and Syowa (69°S, 40°E) are available during the same period. We demonstrate that the temporal evolution of temperature obtained by superposition of the waves derived from SABER measurements accounts for nearly all the temperature variability observed at the longitudes of the three Antarctic stations.
Paleomagnetic determinations on Lanzarote from magnetic and gravity anomalies: Implications for the early history of the Canary Islands
Authors: Blanco‐Montenegro I. , Montesinos F. G. , García A. , Vieira R. , Villalaín J. J.
Published: December 2005

The Bouguer and aeromagnetic anomaly maps of Lanzarote show a gravity high and a dipolar magnetic anomaly over the central part of the island, indicating one isolated source. Assuming that the structure responsible for both anomalies is the same, a methodology has been designed to estimate the total magnetization vector of the source, which is interpreted as a large intrusive body (mafic core) positioned as a result of magma rising to the surface during the early stages of growth of Lanzarote. Considering its geometry to be known from a previous three‐dimensional (3‐D) gravity model, the approach proposed in this paper is based on the delineation of magnetic contacts through analysis of the horizontal gradient of the reduced‐to‐the‐pole anomaly map, comparison between the gravity and the pseudogravity anomalies, and 3‐D forward magnetic modeling. The total magnetization vector obtained by this method is defined by a module of 4.5 A m−1 and a direction D = −20° and I = 30°. Comparing the paleomagnetic pole, obtained from this direction, with the apparent polar wander path of Africa for the last 160 Myr, it is concluded that the main component of the total magnetization vector is probably a primary natural remanent magnetization (NRM) which could have been acquired between 60 and 100 Ma. This result suggests that the emplacement of magmas at shallow depths linked to the beginning of volcanism in Lanzarote took place during the Upper Cretaceous, thus providing the first evidence of a timeline for the early formative stages of this volcanic island.
Phase composition of regional seismic waves from underground nuclear explosions
Authors: Hong Tae‐Kyung , Xie Jiakang
Published: December 2005

The mechanism of regional shear wave excitation by underground nuclear explosions (UNE), a long‐standing issue in nuclear seismology, is investigated by studying the phase composition of regional waves from clustered UNE. Regional seismic waves from 67 UNE at the Balapan test site of Kazakhstan, recorded at station Borovoye, are analyzed with a source array technique under the reciprocity theorem. This analysis allows one to obtain the phase velocity composition of the plane waves leaving the source region. Source locations and the original times are obtained from geodetic measurements, a scaling law between event magnitude and depth, and a calibrated Pn travel time curve. Between frequencies of 0.5 and 3.0 Hz the Pn slowness power spectra are concentrated at a phase velocity (vh) of 8.0 km/s. The expected Sn window contains two dominant phases: a scattered P wave with a vh of around 7.1 km/s and a mantle shear wave with a vh of 4.8 km/s. The Lg waves are coherent between 0.5 and 2.0 Hz, with a dominant vh of 4.2 km/s, which is typical in SmS‐type waves. The Rg wave at frequencies between 0.5 and 0.8 Hz is dominantly composed of a coherent fundamental mode Rayleigh wave with a vh of 3.0 km/s. At higher frequencies (>0.8 Hz) this coherent Rayleigh wave is not observed in the Rg window because of attenuation during wave propagation. The slower vh of Rg and faster vh of Lg, at which the strong coherent peaks in slowness power spectra are observed, suggest that the dominant components of these two waves are different and they are originated differently in the source region. The proposed Rg‐to‐S scattering does not appear to be a dominant mechanism for Lg excitation in the Balapan test site. It is also found that the strength of shear waves contained in the expected Sn window varies with local geology much more than the strength of Lg does. Since the Sn is enriched in high‐frequency (>1 Hz) content as compared to the Lg, this observation suggests that the local geology influences shear wave excitation at high frequencies more than at lower frequencies.
A surface mass balance model for the Greenland Ice Sheet
Authors: Bougamont Marion , Bamber Jonathan L. , Greuell Wouter
Published: December 2005

A surface mass balance model aimed at being coupled to a Global Circulation Model (GCM) for future climate prediction is described and tested for the Greenland Ice Sheet. The model builds on previous modeling designed to be forced by automatic weather station data, and includes surface energy balance as well as processes occurring near the surface such as water percolation and refreezing. Surface albedo is calculated with a new scheme that differentiates the timescale for aging of wet and dry snow and incorporates the effect of a thin layer of water and/or fresh snow at the surface. The model was driven with automatic weather station data from two sites located in the ablation zone in the Kangerlussuaq area (West Greenland), and calculated reasonable annual mass balance values (within 10% in seven out of eight cases) for four individual and consecutive years (1998–2001), using both measured and calculated albedo. This implies that the albedo parameterization is adequate and climate feedbacks affecting the mass balance are well captured. The model was then applied to a distributed 20‐km‐resolution grid covering the whole ice sheet, and forced with 10 years of the European Centre for Medium‐range Weather Forecast (ECMWF) reanalysis (ERA‐40) data. With the aim of coupling the model to a GCM, this study focuses on the ability to model the interannual variability in mass balance rather than to assess the present state of balance of the ice sheet. Modeled spatial and temporal wet zone extent compares well with information derived from passive microwave satellite data.
Linkages among runoff, dissolved organic carbon, and the stable oxygen isotope composition of seawater and other water mass indicators in the Arctic Ocean
Authors: Cooper Lee W. , Benner Ronald , McClelland James W. , Peterson Bruce J. , Holmes Robert M. , Raymond Peter A. , Hansell Dennis A. , Grebmeier Jacqueline M. , Codispoti Louis A.
Published: December 2005

Flow‐weighted dissolved organic carbon (DOC) concentrations and δ18O values were determined from major arctic rivers, specifically the Ob, Yenisey, Lena, Kolyma, Mackenzie, and Yukon during 2003–2004. These data were considered in conjunction with marine data for DOC, δ18O values, nutrients, salinity, and fluorometric indicators of DOC obtained during sampling at the shelf‐basin boundary of the Chukchi and Beaufort seas. On the basis of these data, freshwater in the sampled marine waters is likely derived from regional sources, such as the Mackenzie, the Bering Strait inflow, and possibly eastern Siberian rivers, including the Kolyma, or the Lena, but not rivers farther west in the Eurasian arctic. Freshwater from melted sea ice is insignificant over annual cycles, although melted sea ice was a locally dominant freshwater component following summer sea‐ice retreat in 2002. DOC concentrations were correlated with the runoff fraction, with an apparent meteoric water DOC concentration of 174 ± 1 μM. This is lower than the flow‐weighted concentrations measured at river mouths of the five largest Arctic rivers (358 to 917 μM), indicating removal of DOC during transport through estuaries, shelves and in the deep basin. Flow‐weighted DOC concentrations in the two largest North American arctic rivers, the Yukon (625 μM) and the Mackenzie (358 μM), are lower than in the three largest Eurasian arctic rivers, the Ob (825 μM), the Yenesey (858 μM), and the Lena (917 μM). A fluorometer responding to chromophoric dissolved organic matter (CDOM) was not correlated with DOC concentrations in Pacific‐influenced surface waters unlike previous observations in the Atlantic layer. Nutrient distributions, concentrations, and derived ratios suggest the CDOM fluorometer may be responding to the release of chromophoric materials from shelf sediments. Shipboard incubations of undisturbed sediment cores indicate that sediments on the Bering and Chukchi Sea shelves are a net source of DOC to the Arctic Ocean.
Role of cysteine residues in the function of human UDP glucuronosyltransferase isoform 1A1 (UGT1A1)
Authors: Ghosh Siddhartha S. , Lu Yang , Lee Sung W. , Wang Xia , Guha Chandan , Roy-Chowdhury Jayanta , Roy-Chowdhury Namita
Published: December 2005

Bilirubin glucuronidation, catalysed by UGT1A1 [UGT (UDP glucuronosyltransferase) isoform 1A1, EC 2.4.1.17], is critical for biliary elimination of bilirubin. UGT1A1 deficiency causes CN-1 (Crigler–Najjar syndrome type 1), which is characterized by potentially lethal unconjugated hyperbilirubinaemia. Nucleotide sequence analysis of UGT1A1 in two CN-1 patients revealed that patient A was homozygous for a nt 530 G→A (where nt 530 G→A means guanine to adenine transition at nucleotide 530) mutation, predicting a C177Y substitution, and patient B had a nt 466 T→C mutation on one allele and a nt 1070 A→G mutation on the other, predicting a C156R and a Q357R substitution respectively. All 11 cysteine residues of mature human UGT1A1 are highly conserved in other human UGT isoforms and in rat, mouse and Rhesus monkey UGT1A1, suggesting their functional importance. Expression of mutagenized UGT1A1 plasmids showed that substitution of any of the seven cysteine residues located within the endoplasmic reticulum cisternae (including those mutated in patients A and B) abolished UGT1A1 activity or markedly increased its apparent Km for bilirubin. Substitution of the three cysteine residues within the C-terminal cytosolic tail had minimal effect on basal UGT1A1 activity, but prevented UGT1A1 activation by UDP-GlcNAc. N-Ethylmaleimide did not inhibit UGT1A1 activity in native microsomes, but prevented UGT1A1 activation by UDP-GlcNAc and inhibited the activity in digitonin-permeabilized microsomes. Dithiothreitol did not affect UGT1A1 activity in human liver microsomes. Together, the results suggested that free thiol groups, but not disulphide bonding, of seven cysteine residues within the intracisternal region of human UGT1A1 are important for its catalytic activity, while cysteine residues in the cytosolic domain may be involved in its physiological activation by UDP-GlcNAc.
Inhibition of enzyme activity of and cell-mediated substrate cleavage by membrane type 1 matrix metalloproteinase by newly developed mercaptosulphide inhibitors
Authors: Hurst Douglas R. , Schwartz Martin A. , Jin Yonghao , Ghaffari Mohammad A. , Kozarekar Pallavi , Cao Jian , Sang Qing-Xiang Amy
Published: December 2005

MT1-MMP (membrane type 1 matrix metalloproteinase, or MMP-14) is a key enzyme in molecular carcinogenesis, tumour-cell growth, invasion and angiogenesis. Novel and potent MMP inhibitors with a mercaptosulphide zinc-binding functionality have been designed and synthesized, and tested against human MT1-MMP and other MMPs. Binding to the MT1-MMP active site was verified by the competitive-inhibition mechanism and stereochemical requirements. MT1-MMP preferred deep P1′ substituents, such as homophenylalanine instead of phenylalanine. Novel inhibitors with a non-prime phthalimido substituent had Ki values in the low-nanomolar range; the most potent of these inhibitors was tested and found to be stable against air-oxidation in calf serum for at least 2 days. To illustrate the molecular interactions of the inhibitor–enzyme complex, theoretical docking of the inhibitors into the active site of MT1-MMP and molecular minimization of the complex were performed. In addition to maintaining the substrate-specificity pocket (S1′ site) van der Waals interactions, the P1′ position side chain may be critical for the peptide-backbone hydrogen-bonding network. To test the inhibition of cell-mediated substrate cleavage, two human cancer-cell culture models were used. Two of the most potent inhibitors tested reached the target enzyme and effectively inhibited activation of proMMP-2 by endogenous MT1-MMP produced by HT1080 human fibrosarcoma cells, and blocked fibronectin degradation by prostate cancer LNCaP cells stably transfected with MT1-MMP. These results provide a model for mercaptosulphide inhibitor binding to MT1-MMP that may aid in the design of more potent and selective inhibitors for MT1-MMP.
Influence of the chemistry of conjugation of poly(ethylene glycol) to Hb on the oxygen-binding and solution properties of the PEG-Hb conjugate
Authors: Hu Tao , Prabhakaran Muthuchidambaram , Acharya Seetharama A. , Manjula Belur N.
Published: December 2005

Our recent studies on PEG–Hb [poly(ethylene glycol)–Hb] conjugates generated by thiolation-mediated maleimide-chemistry based PEGylation demonstrated that the vasoactivity of the PEG–Hb conjugates is a function of the configuration of the PEG chains on the surface of the protein and is independent of the PEG/protein-mass ratio [Manjula, A. G. Tsai, Intaglietta, H.-C. Tsai, Ho, Smith, Perumalsamy, Kanika, Friedman and Acharya (2005) Protein J. 24, 133–146]. A Hb conjugated with six PEG5k chains (SP-PEG5k)6-Hb, was vasoinactive. In an attempt to understand whether the chemistry of conjugation of PEG to Hb has any influence on the modulation of its functional and solution properties, we have now generated a new hexaPEGylated-Hb, (propyl-PEG5k)6-Hb, by reductive alkylation chemistry. CD (circular dichroism) spectral measurements indicated that the overall secondary structure of Hb is not adversely influenced upon PEGylation. (Propyl-PEG5k)6-Hb exhibited an increased O2 affinity with decreased co-operativity and decreased modulation by allosteric effectors comparable with that of (SP-PEG5k)6-Hb, although its Cys-93(β) is not derivatized as in the latter. On a molecular mass basis, PEG linked to Hb by reductive alkylation increased its COP (colloidal osmotic pressure) more efficiently than when linked by thiolation-mediated maleimide-chemistry. These results demonstrate that the functional properties of PEG–Hb conjugates may be a direct consequence of surface decoration of Hb with PEG, but are independent of the site (pattern) and/or the chemistry of PEGylation. However the solution properties of PEGylated Hb are influenced by the site (pattern) and/or the chemistry of PEGylation and the presence or absence of an ‘extension arm’ between the conjugating site of Hb and the PEG chain.
Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles
Authors: Gagné Jean-Philippe , Bonicalzi Marie-Ève , Gagné Pierre , Ouellet Marie-Ève , Hendzel Michael J. , Poirier Guy G.
Published: December 2005

PARG [poly(ADP-ribose) glycohydrolase] is the only known enzyme that catalyses the hydrolysis of poly(ADP-ribose), a branched polymer that is synthesized by the poly(ADP-ribose) polymerase family of enzymes. Poly(ADP-ribosyl)ation is a transient post-translational modification that alters the functions of the acceptor proteins. It has mostly been studied in the context of DNA-damage signalling or DNA transaction events, such as replication and transcription reactions. Growing evidence now suggests that poly(ADP-ribosyl)ation could have a much broader impact on cellular functions. To elucidate the roles that could be played by PARG, we performed a proteomic identification of PARG-interacting proteins by mass spectrometric analysis of PARG pulled-down proteins. In the present paper, we report that PARG is resident in FMRP (Fragile-X mental retardation protein)-associated messenger ribonucleoparticles complexes. The localization of PARG in these complexes, which are components of the translation machinery, was confirmed by sedimentation and microscopy analysis. A functional link between poly(ADP-ribosyl)ation modulation and FMRP-associated ribonucleoparticle complexes are discussed in a context of translational regulation.
The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae
Authors: Cavero Santiago , Traba Javier , Del Arco Araceli , Satrústegui Jorgina
Published: December 2005

Sal1p is a mitochondrial protein that belongs to the SCaMC (short calcium-binding mitochondrial carrier) subfamily of mitochondrial carriers. The presence of calcium-binding motifs facing the extramitochondrial space allows the regulation of the transport activity of these carriers by cytosolic calcium and provides a new mechanism to transduce calcium signals in mitochondria without the requirement of calcium entry in the organelle. We have studied its transport activity, finding that it is a carboxyatractyloside-resistant ATP-Mg carrier. Mitochondria from a disruption mutant of SAL1 have a 50% reduction in the uptake of ATP. We have also found a clear stimulation of ATP-transport activity by calcium, with an S0.5 of approx. 30 μM. Our results also suggest that Sal1p is a target of the glucose-induced calcium signal which is non-essential in wild-type cells, but becomes essential for transport of ATP into mitochondria in yeast lacking ADP/ATP translocases.
Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1
Authors: Stiburek Lukas , Vesela Katerina , Hansikova Hana , Pecina Petr , Tesarova Marketa , Cerna Leona , Houstek Josef , Zeman Jiri
Published: December 2005

The biogenesis of eukaryotic COX (cytochrome c oxidase) requires several accessory proteins in addition to structural subunits and prosthetic groups. We have analysed the assembly state of COX and SCO2 protein levels in various tissues of six patients with mutations in SCO2 and SURF1. SCO2 is a copper-binding protein presumably involved in formation of the CuA centre of the COX2 subunit. The function of SURF1 is unknown. Immunoblot analysis of native gels demonstrated that COX holoenzyme is reduced to 10–20% in skeletal muscle and brain of SCO2 and SURF1 patients and to 10–30% in heart of SCO2 patients, whereas liver of SCO2 patients' contained normal holoenzyme levels. The steady-state levels of mutant SCO2 protein ranged from 0 to 20% in different SCO2 patient tissues. In addition, eight distinct COX subcomplexes and unassembled subunits were found, some of them identical with known assembly intermediates of the human enzyme. Heart, brain and skeletal muscle of SCO2 patients contained accumulated levels of the COX1·COX4·COX5A subcomplex, three COX1-containing subcomplexes, a COX4·COX5A subcomplex and two subcomplexes composed of only COX4 or COX5A. The accumulation of COX1·COX4·COX5A subcomplex, along with the virtual absence of free COX2, suggests that the lack of the CuA centre may result in decreased stability of COX2. The appearance of COX4·COX5A subcomplex indicates that association of these nucleus-encoded subunits probably precedes their addition to COX1 during the assembly process. Finally, the consequences of SCO2 and SURF1 mutations suggest the existence of tissue-specific functional differences of these proteins that may serve different tissue-specific requirements for the regulation of COX biogenesis.
Regulation of the localization and activity of inositol 1,4,5-trisphosphate 3-kinase B in intact cells by proteolysis
Authors: Yu Jowie C. H. , Lloyd-Burton Samantha M. , Irvine Robin F. , Schell Michael J.
Published: December 2005

IP3K (inositol 1,4,5-trisphosphate 3-kinase) catalyses the Ca2+-regulated phosphorylation of the second messenger Ins(1,4,5)P3, thereby inactivating the signal to release Ca2+ and generating Ins(1,3,4,5)P4. Here we have investigated the localization and activity of IP3KB and its modulation by proteolysis. We found that the N- and C-termini (either side of residue 262) of IP3KB localized predominantly to the actin cytoskeleton and ER (endoplasmic reticulum) respectively, both in COS-7 cells and in primary astrocytes. The functional relevance of this was demonstrated by showing that full-length (actin-localized) IP3KB abolished the histamine-induced Ca2+ response in HeLa cells more effectively than truncated constructs localized to the ER or cytosol. The superior efficacy of full-length IP3KB was also attenuated by disruption of the actin cytoskeleton. By transfecting COS-7 cells with double-tagged IP3KB, we show that the translocation from actin to ER may be a physiologically regulated process caused by Ca2+-modulated constitutive proteolysis in intact cells.
The effect of N-terminal truncation on double-dimer assembly of goose δ-crystallin
Authors: Lee Hwei-Jen , Lai Young-Hsang , Wu Su-Ying , Chen Yu-Hou
Published: December 2005

δ-Crystallin is a soluble structural protein in avian eye lenses that confers special refractive properties. In the presence of GdmCl (guanidinium chloride), tetrameric δ-crystallin undergoes dissociation via a dimeric state to a monomeric molten globule intermediate state. The latter are denatured at higher GdmCl concentrations in a multi-state manner. In the present study, the X-ray structure of goose δ-crystallin was determined to 2.8 Å (1 Å=0.1 nm). In this structure the first 25 N-terminal residues interact with a hydrophobic cavity in a neighbouring molecule, stabilizing the quaternary structure of this protein. When these 25 residues were deleted this did not produce any gross structural changes, as judged by CD analysis, but slightly altered tryptophan fluorescence and ANS (8-anilino-1-naphthalenesulphonic acid) spectra. The dimeric form was significantly identified as judged by sedimentation velocity and nondenaturing gradient gel electrophoresis. This mutant had increased sensitivity to temperature denaturation and GdmCl concentrations of 0.3–1.0 M. This protein was destabilized about 3.3 kcal/mol (1 kcal=4.184 kJ) due to N-terminal truncation. After incubation at 37 °C N-terminal truncated proteins were prone to aggregation, suggesting the presence of the unstable dimeric conformation. An important role for the N-terminus in dimer assembly of goose δ-crystallin is proposed.
Specific conformational changes of plasminogen induced by chloride ions, 6-aminohexanoic acid and benzamidine, but not the overall openness of plasminogen regulate, production of biologically active angiostatins
Authors: Warejcka Debra J. , Twining Sally S.
Published: December 2005

The overall conformation of plasminogen depends upon the presence of anions and molecules such as AHA (6-aminohexanoic acid) and BZ (benzamidine). The purpose of the present study was to determine the effect of conformation on the initial and secondary cleavages of plasminogen to generate active angiostatins. Plasminogen was digested with the physiologically relevant neutrophil elastase in one of the four Tris/acetate buffers: buffer alone or buffer plus NaCl, AHA or BZ. The initial cleavage of Glu1-plasminogen was much slower in the tight NaCl-induced α-conformation, fastest in the intermediate BZ-induced β-conformation and intermediate both in the control and in the AHA-induced open γ-conformation. Although the buffer system determined the relative amounts of the initial cleavage products, the same four cleavage sites were utilized under all conditions. A fifth major initial cleavage within the protease domain was observed in the presence of BZ. N-terminal peptide cleavage required for angiostatin formation occurred as either the initial or the secondary cleavage. Angiostatins were generated fastest in the presence of BZ and slowest in the presence of NaCl. Both the initial and secondary cleavages were affected by the modifying agents, indicating that they influence the conformation of both Glu-plasminogen and the initial cleavage products. The angiostatins produced under the different conditions inhibited proliferation of human umbilical-vein endothelial cells. These results suggest that plasminogen conversion into active angiostatins is dependent more on the specific conformation changes induced by the various modifying reagents rather than on the overall openness of the molecule.
Trafficking defects of the Southeast Asian ovalocytosis deletion mutant of anion exchanger 1 membrane proteins
Authors: Cheung Joanne C. , Cordat Emmanuelle , Reithmeier Reinhart A. F.
Published: December 2005

Human AE1 (anion exchanger 1) is a membrane glycoprotein found in erythrocytes and as a truncated form (kAE1) in the BLM (basolateral membrane) of α-intercalated cells of the distal nephron, where they carry out electroneutral chloride/bicarbonate exchange. SAO (Southeast Asian ovalocytosis) is a dominant inherited haematological condition arising from deletion of Ala400–Ala408 in AE1, resulting in a misfolded and transport-inactive protein present in the ovalocyte membrane. Heterozygotes with SAO are able to acidify their urine, without symptoms of dRTA (distal renal tubular acidosis) that can be associated with mutations in kAE1. We examined the effect of the SAO deletion on stability and trafficking of AE1 and kAE1 in transfected HEK-293 (human embryonic kidney) cells and kAE1 in MDCK (Madin–Darby canine kidney) epithelial cells. In HEK-293 cells, expression levels and stabilities of SAO proteins were significantly reduced, and no mutant protein was detected at the cell surface. The intracellular retention of AE1 SAO in transfected HEK-293 cells suggests that erythroid-specific factors lacking in HEK-293 cells may be required for cell-surface expression. Although misfolded, SAO proteins could form heterodimers with the normal proteins, as well as homodimers. In MDCK cells, kAE1 was localized to the cell surface or the BLM after polarization, while kAE1 SAO was retained intracellularly. When kAE1 SAO was co-expressed with kAE1 in MDCK cells, kAE1 SAO was largely retained intracellularly; however, it also co-localized with kAE1 at the cell surface. We propose that, in the kidney of heterozygous SAO patients, dimers of kAE1 and heterodimers of kAE1 SAO and kAE1 traffic to the BLM of α-intercalated cells, while homodimers of kAE1 SAO are retained in the endoplasmic reticulum and are rapidly degraded. This results in sufficient cell-surface expression of kAE1 to maintain adequate bicarbonate reabsorption and proton secretion without dRTA.
Calculation of the entropy of random coil polymers with the hypothetical scanning Monte Carlo method
Authors: White Ronald P. , Meirovitch Hagai
Published: December 2005

Hypothetical scanning Monte Carlo (HSMC) is a method for calculating the absolute entropy S and free energy F from a given MC trajectory developed recently and applied to liquid argon, TIP3P water, and peptides. In this paper HSMC is extended to random coil polymers by applying it to self-avoiding walks on a square lattice—a simple but difficult model due to strong excluded volume interactions. With HSMC the probability of a given chain is obtained as a product of transition probabilities calculated for each bond by MC simulations and a counting formula. This probability is exact in the sense that it is based on all the interactions of the system and the only approximation is due to finite sampling. The method provides rigorous upper and lower bounds for F, which can be obtained from a very small sample and even from a single chain conformation. HSMC is independent of existing techniques and thus constitutes an independent research tool. The HSMC results are compared to those obtained by other methods, and its application to complex lattice chain models is discussed; we emphasize its ability to treat any type of boundary conditions for which a reference state (with known free energy) might be difficult to define for a thermodynamic integration process. Finally, we stress that the capability of HSMC to extract the absolute entropy from a given sample is important for studying relaxation processes, such as protein folding.
Area compressibility and buckling of amphiphilic bilayers in molecular dynamics simulations
Authors: den Otter W. K.
Published: December 2005

The elastic modulus or area compressibility of a membrane is routinely calculated in molecular dynamics simulations as the proportionality constant relating surface tension and projected surface area. Recent studies, however, have revealed a marked system size dependence of these moduli, which we attribute to the neglect of thermal undulations in the area calculation. We discuss several methods, based on the Helfrich model and on numerical triangulation, to remedy this situation, and find a satisfying agreement between them. The Helfrich model also quantitatively describes a buckling transition observed for compressed bilayers.
Static and dynamic descriptions of bond breaking/formation: A complementary view?
Authors: Joubert Laurent , Adamo Carlo
Published: December 2005

Ab initio molecular-dynamic simulations using density-functional theory and the recent atom-centered density-matrix propagation (ADMP) method were used to study the bond breaking and formation for a case-study substitution nucleophilic bimolecular reaction, namely, the Walden inversion. Using the atoms-in-molecule approach, we have performed a detailed analysis to investigate intra- and intermolecular charge transfer along the ADMP trajectory. These results were compared to those obtained considering a static approach, such as the intrinsic reaction path. In particular, the topological properties computed along the dynamic trajectory well evidence a stronger electron exchange tending to spontaneously maximize the rising covalent interaction. Furthermore, their analysis suggests that the bond formation mechanism involves a reactive intermediate with a bonding interaction stronger than in the final product.
Photoinduced ion-pair formation in the (HI)m(H2O)n cluster system
Authors: Dermota T. E. , Hydutsky D. P. , Bianco N. J. , Castleman A. W.
Published: December 2005

The temporal behavior of the photoinduced ion-pair formation process in the (HI)m(H2O)n (n=1–6 for m=1 and n=1–4 for m=2) cluster system has been studied via the coupling between the gΣ−3 Rydberg and VΣ+1 valence states. Comparison of the time constants obtained to those measured in previous experiments for the analogous process in HBr-water clusters, along with a detailed analysis of the signal intensity as a function of laser-pulse power, provides new insight into and confirmation of the previously proposed ion-pair formation mechanism.
Ion energy distributions in a pulsed plasma doping system
Authors: Radovanov S. , Godet L. , Dorai R. , Fang Z. , Koo B. W. , Cardinaud C. , Cartry G. , Lenoble D. , Grouillet A.
Published: December 2005

Discharge parameters in a pulsed dc plasma doping system have been studied using measurements of time-resolved ion energy distributions, relative ion density, plasma potential, and electron temperature in BF3 and Ar plasmas during active discharge and afterglow periods. Negative plasma potentials are observed when using a hollow cathode to create a plasma while implanting at ultralow energies (<500eV). The kinetics of ion generation and decay in BF3 during the pulse on and off periods have been discussed.
Highly stable organic light-emitting devices with a uniformly mixed hole transport layer
Authors: Tsai Chih-Hung , Liao Chi-Hung , Lee Meng-Ting , Chen Chin H.
Published: December 2005

Highly stable organic light-emitting devices were made by using a uniformly mixed hole transport layer (UM-HTL) composed of a mixture of 2-methyl-9,10-di(2-naphthyl)anthracene (MADN) and N,N′-bis(1-naphthyl)-N,N′-diphenyl,1,1′-biphenyl-4,4′-diamine (NPB) in a 3:7 (MADN:NPB) ratio. The lifetime of 10-(2-benzothiazolyl)-1,1,7,7-tetramethyl-2,3,6,7-tetrahydro-1H,5H,11H-benzo[l]-pyrano[6,7,8-ij]quinolizin-11-one doped green device with UM-HTL can be greatly improved to 2.7 times longer than that of the conventional device (NPB based HTL) without impacting on its driving voltage and emissive color significantly. This improvement in stability can be attributed to the fact that the unstable [Alq3+] species formed by electro-oxidation have been effectively suppressed.
Effect of surface bond-order loss on the electronic thermal conductivity of metallic polycrystalline films
Authors: Au Yeung T. C. , Chiam T. C. , Sun Chang Q. , Gu Mingxia , Shangguan W. Z. , Kam C. H.
Published: December 2005

The effect of surface bond-order loss on the electronic thermal conductivity of metallic polycrystalline films is examined using Boltzmann transport theory. A modification of the grain boundary potential barrier has been made by adding depressed potential wells of intra-atomic trapping [C. Q. Sun, Phys. Rev. B 69, 045105 (2004)] to both sides of the grain boundaries. Electron scattering by film surfaces is also considered to follow the line of Fuchs’ convention. Results show that the thermal conductivity of the films is sensitive to the film thickness, mean grain size, and Fermi energy. In particular, thermal conductivity increases significantly with the depth of the atomic trapping due to the bond-order loss induced surface bond contraction and associated bond strength gain.