bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping of bibliographical standards into XML
Authors: Jakšić Mirjana
Published: June 2004

The most popular bibliographical standards, which prescribe the exchange of bibliographical data in machine readable form, are MARC (Machine Readable Cataloguing) and UNIMARC (Universal Machine Readable Cataloguing). This paper presents two schemas, both written in the XML schema language: the UNIMARC format schema and the XML bibliographical records schema. The instance of the UNIMARC format schema is an XML document of UNIMARC format. This schema provides easier updating and adjusting of the UNIMARC format at the national or regional level. It was also the basis for the development of the XML editor for UNIMARC format description. The instance of the XML bibliographical records schema is an XML bibliographic record. This schema provides very thorough control of the contents and structure of bibliographical records, whether they were directly created as XML records or converted to XML from existing UNIMARC records. The validation process is implemented in the Java environment, with the Sun Multi‐Schema XML Validator (MSV) package. The author is aware of the inevitable question of redundant information contained in these two schemas and proposes some possible solutions. Copyright © 2004 John Wiley & Sons, Ltd.
Partial redundancy elimination for access expressions by speculative code motion
Authors: Kawahito Motohiro , Komatsu Hideaki , Nakatani Toshio
Published: June 2004

We present a new memory access optimization for Java to perform aggressive code motion for speculatively optimizing memory accesses by applying partial redundancy elimination (PRE) techniques. First, to reduce as many barriers as possible and to enhance code motion, we perform alias analysis to identify all the regions in which each object reference is not aliased. Secondly, we find all the possible barriers. Finally, we perform code motions in three steps. For the first step, we apply a non‐speculative PRE algorithm to move load instructions and their following instructions in the backwards direction of the control flow graph. For the second step, we apply a speculative PRE algorithm to move some of them aggressively before the conditional branches. For the third step, we apply our modified version of a non‐speculative PRE algorithm to move store instructions in the forward direction of the control flow graph and to even move some of them after the merge points. We implemented our new algorithm in our production‐level Java just‐in‐time compiler. Our experimental results show that our speculative algorithm improves the average (maximum) performance by 13.1% (90.7%) for jBYTEmark and 1.4% (4.4%) for SPECjvm98 over the fastest algorithm previously described, while it increases the average (maximum) compilation time by 0.9% (2.9%) for both benchmark suites. Copyright © 2004 John Wiley & Sons, Ltd.
Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration
Authors: Ding Yu‐Shin , Gatley S. John , Thanos Panayotis K. , Shea Colleen , Garza Victor , Xu Youwen , Carter Pauline , King Payton , Warner Don , Taintor Nicholas B. , Park Daniel J. , Pyatt Bea , Fowler Joanna S. , Volkow Nora D.
Published: June 2004

Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d‐ and l‐threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d‐isomer. A recent report that intraperitoneally (i.p.) administered l‐threo‐MP displayed potent, dose‐dependent inhibition of cocaine‐ or apomorphine‐induced locomotion in rats, raises the question of whether l‐threo‐MP has a similar effect when given orally. It has been speculated that l‐threo‐MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l‐threo‐MP or its metabolites can be delivered to the brain when it is given orally, and whether l‐threo‐MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C‐11‐labeled d‐ and l‐threo‐MP ([methyl‐11C]d‐threo‐MP and [methyl‐11C]l‐threo‐MP). In addition, we assessed the effects of i.p. l‐threo‐MP on spontaneous and cocaine‐stimulated locomotor activity in mice. There was a higher global uptake of carbon‐11 in both baboon and rat brain for oral [11C]l‐threo‐MP than for oral [11C]d‐threo‐MP. Analysis of the chemical form of radioactivity in rat brain after [11C]d‐threo‐MP indicated mainly unchanged tracer, whereas with [11C]l‐threo‐MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [11C]methanol or [11C]CO2, derived from demethylation, was excluded by ex vivo studies in rats. When l‐threo‐MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l‐threo‐MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and enters the brain after oral administration, but that l‐threo‐MP may not be pharmacologically active. These results are pertinent to the question of whether l‐threo‐MP contributes to the behavioral and side effect profile of MP during treatment of ADHD. Synapse 53:168–175, 2004. © 2004 Wiley‐Liss, Inc.
The First Requirements Elucidator Demonstration (FRED) tool
Authors: Kasser Joseph E.
Published: June 2004

The problem of poorly written requirements has been documented for at least the last ten years without much improvement. This paper describes applying technology in the form of a simple software tool containing an Expert System that can minimize the production of poorly worded requirements in the future and help ensure the completeness of the testing of poorly worded requirements. This paper also describes how the tool evolved and discusses how the tool can be used to prevent cost and schedule escalations due to some types of poorly worded requirements. © 2004 Wiley Periodicals, Inc. Syst Eng 7: 243–256, 2004
Viewing systems from a business management perspective: The ISO/IEC 15288 standard
Authors: Arnold Stuart , Lawson Harold W.
Published: June 2004

The scope of systems engineering as a discipline and profession is changing. Though the classical focus has been on technical systems, there is a pressing need to also apply a systems engineering approach to nontechnical systems. In addition, there is an increasing emphasis placed upon the management dimension of systems engineering and its impact on business and trade. To meet these new directions, an instrument is needed which can guide enterprises in dealing with the life cycle of all types of systems. This article presents factors related to ISO/IEC 15288's contribution as a guiding instrument for leading the engineering and management of systems in these new directions. © 2004 Wiley Periodicals, Inc. Syst Eng 7: 229–242, 2004
Serum indices of body stores of iron in northern fur seals (Callorhinus ursinus) and their relationship to hemochromatosis
Authors: Mazzaro Lisa M. , Dunn J. Lawrence , St. Aubin David J. , Andrews Gordon A. , Chavey Patricia S.
Published: June 2004

Iron storage disease (hemochromatosis) has been reported in many species of both captive and free‐ranging animals. In this study we examined the relationship between this disease and concentrations of iron analytes in aquarium‐held northern fur seals (Callorhinus ursinus). Sera were analyzed for iron, total iron‐binding capacity (TIBC), ferritin, ceruloplasmin, and haptoglobin concentrations in a retrospective study that included samples taken over a 14‐year period. The animals ranged in age from <1 year to an estimated 23 years. Serum ferritin was measured using an enzyme‐linked immunosorbent assay (ELISA) for canine sera. The results from this assay are the first reported for any pinniped. Serum iron concentrations in presumed healthy animals ranged from 37 to 196 µg/dl, and TIBC ranged from 136 to 484 µg/dl. The transferrin saturation percentage differed significantly between male (41%) and female (63%) adult fur seals, as did the ferritin levels (54 ng/ml for males vs. 500 ng/ml for females). There was a trend toward increased serum ferritin and percent transferrin saturation with age, especially in females. The data also showed a relationship between serum iron and transferrin saturation among eight mother–pup pairs, which suggests that pups may develop increased iron levels due to placental transfer of iron and/or transfer of iron through the milk from iron‐overloaded females. Diet was considered as a factor in the development of hemochromatosis in at least three geriatric female northern fur seals, and their diets were analyzed for iron concentrations. On the basis of these results, the diets were altered by replacing a portion of the high‐iron‐content fish (herring) with a lower‐iron‐content item (squid), and discontinuing iron and vitamin C supplementation (via a multivitamin tablet). Sera were analyzed before, and 1 and 4 years after the dietary changes were implemented. Paired t‐tests showed no significant changes in the iron analytes from pre‐ to post‐diet‐change samples, which indicates that it may be too late to affect iron levels by diet alone in older animals with a chronic history of elevated iron levels. Zoo Biol 23:205–218, 2004. © 2004 Wiley‐Liss, Inc.
Characteristics and in vitro fertilizing ability of giant panda (Ailuropoda melanoleuca) frozen‐thawed epididymal spermatozoa obtained 4 hours postmortem: A case report
Authors: Pérez‐Garnelo Sonia S. , Garde Julián , Pintado Belén , Borque Concepción , Talavera Covadonga , Delclaux María , López Manuel , Martínez Julio De La Fuente
Published: June 2004

When Chu‐Lin, a male giant panda (studbook #249), died at Madrid Zoo, his reproductive tract was removed 4 hr postmortem and the epididymal spermatozoa were collected. Extended sperm were kept at 5°C for 4 hr, loaded into straws, and frozen for 7 min in liquid nitrogen vapor before the straws were plunged into liquid nitrogen. Two straws were thawed and evaluated. Sperm motility was assessed in fresh, refrigerated, and thawed spermatozoa (75%, 60%, 35%, respectively). Sperm viability and acrosome status were estimated using a triple‐stain technique (TST). The results showed 33% live sperm with intact acrosomes after thawing. A hypoosmotic swelling (HOS) test demonstrated the retention of membrane integrity in 72% of thawed sperm. To evaluate the in vitro fertilizing ability of thawed sperm, a sperm penetration assay (SPA) was performed. The values obtained for the percentage of penetration and the penetration index were 62% and 1.78 sperm/oocyte, respectively. The results obtained demonstrate that epididymal sperm recovered from a giant panda postmortem can be successfully cryopreserved. The sperm fertilizing ability demonstrated in vitro after thawing may provide a final opportunity for this male to contribute to the currently small germplasm reserves of this endangered species, and to reproduce in the future through assisted reproductive technology. Zoo Biol 23:279–285, 2004. © 2004 Wiley‐Liss, Inc.
Proximate, vitamins A and E, and mineral composition of free‐ranging cotton mice (Peromyscus gossypinus) from St. Catherines Island, Georgia
Authors: Thomas Jasmine , Glatt Batsheva , Dierenfeld Ellen S.
Published: June 2004

Although rodents are an integral part of numerous carnivore diets, there is little published information regarding nutrient composition in free‐ranging mice for comparison with laboratory‐reared prey. Cotton mice (Peromyscus gossypinus, n=6) were captured on St. Catherines Island, Georgia, and analyzed for water, ash, protein, and fat content (proximate constituents), as well as minerals and the fat‐soluble vitamins A and E. The overall body composition (mean±SD: 65.8%±1.9% water, 10.9%±2.2% ash, 56.4%±4.1% protein, and 27.2%±3.9% fat) was similar to published values for adult laboratory mice (Mus domesticus). The macro‐ (Ca, K, Mg, Na, and P) and trace (Cu, Fe, Mn, and Zn) mineral levels were also similar to previously reported values for laboratory mice, and in general met or exceeded the established nutrient requirements for domestic carnivores. Vitamin E ranged from 77 to 170 IU/kg dry matter (DM) in these mice–again, similar to values previously quantified in laboratory mice. However, the vitamin A concentrations (21,947±6,893 IU/kg DM) in the free‐ranging mice were consistently and substantially lower than values reported for whole laboratory mice. To our knowledge, this is the first quantification of vitamin A in free‐ranging mice used as prey by carnivores. While other nutrients measured were similar between captive‐reared and free‐ranging mice, the current data suggest the need for further investigation of vitamin A nutrition in the development of optimal diets for carnivores in captivity. Zoo Biol 23:253–261, 2004. © 2004 Wiley‐Liss, Inc.
Effect of different primate species on germination of Ficus (Urostigma) seeds
Authors: Righini Nicoletta , Serio‐Silva Juan Carlos , Rico‐Gray Victor , Martínez‐Mota Rodolfo
Published: June 2004

We examined the germination of Ficus seeds (subgenus Urostigma) after defecation by six primate species (New World monkeys, Old World monkeys, and apes). Seeds from figs (control) and primate feces were placed in a thermostatically controlled chamber for 30 days. Seeds defecated by Alouatta palliata, A. pigra, and Cercopithecus aethiops showed significantly higher germination rates than control seeds. In addition, seeds from A. palliata feces germinated significantly faster than control seeds and seeds from C. aethiops and Pan troglodytes. These differences may be due to the different digestive characteristics of the six primate species. Zoo Biol 23:273–278, 2004. © 2004 Wiley‐Liss, Inc.
Psychosocial functioning in patients with treatment resistant depression
Authors: Petersen Timothy , Papakostas George I. , Mahal Yasmin , Guyker Wendy M. , Beaumont Erin C. , Alpert Jonathan E. , Fava Maurizio , Nierenberg Andrew A.
Published: May 2004

Background

Depression is a disorder that causes disability, with a profound adverse impact on all areas of psychosocial functioning. This is particularly true for those with treatment resistant depression (TRD). However, to date, no systematic assessments of psychosocial functioning for patients with TRD have been conducted.

Methods

In the present study, we used the Longitudinal Interval Follow-up Evaluation (LIFE) scale to measure psychosocial functioning in 92 patients with TRD. These patients met formal criteria for TRD and were part of a clinical trial examining the efficacy of lithium augmentation of nortriptyline.

Results

Clinicians rated this sample of patients as experiencing mild to moderate impairment in work-related activities, good to fair interpersonal relations, poor level of involvement in recreational activities, and mild impairment of ability to enjoy sexual activity. Patients and clinicians rated global social adjustment as poor.

Conclusions

Patients with formally defined TRD experience significant impairment in psychosocial functioning. In this sample a tendency existed for both clinicians and patients to assign more severely impaired global ratings when compared with ratings for specific functional areas.
Rapid slip along the central Altyn Tagh Fault: Morphochronologic evidence from Cherchen He and Sulamu Tagh
Authors: Mériaux A.‐S. , Ryerson F. J. , Tapponnier P. , Van der Woerd J. , Finkel R. C. , Xu Xiwei , Xu Zhiqin , Caffee M. W.
Published: June 2004

To better constrain the ongoing rates of deformation in northern Tibet, the ages of fluvial and glacial geomorphic markers left‐laterally displaced by the Altyn Tagh Fault have been determined by radiocarbon and 10Be‐26Al cosmic ray exposure dating. Two sites were investigated: Cherchen He and Sulamu Tagh, both near Tura (∼37.6°N, 86.6°E). The sites are geomorphologically distinct with Cherchen He dominated by fluvial processes and the Sulamu Tagh by glacial action. Nine offsets ranging from 166 to 3660 m with ages between 6 and 113 ka yield an average slip rate of 26.9 ± 6.9 mm/yr. Landscape evolution appears to have been modulated by climate change and is temporally consistent with the δ18O record from the Guliya ice cap in the West Kunlun; the features of interest were all formed by glacial and fluvial processes subsequent to marine isotope stage 5e, with the youngest features having formed during the early Holocene Optimum. This “near‐field,” morphochronological slip rate is averaged over many earthquake cycles and is hence little affected by interseismic strain. It is kinematically consistent with other, somewhat lower, geomorphic slip rate measurements to the east. The average rate, and lower bounds obtained from alternate interpretational models, 18.4 mm/yr, cannot be reconciled with the most rece geodetic measurements (∼7 mm/yr), suggesting that interseismic strain and interactions with adjacent faults may lead to disparate geologic and geodetic rate estimates. This late Pleistocene‐Holocene, morphochronologic rate would imply that, at this longitude, the Altyn Tagh Fault, on the north edge of Tibet, might absorb almost as much of India's convergence relative to Siberia as the Himalayan Main Frontal Thrust does on the southern edge of the plateau.
Spectroscopic measurements of NO2 in a Colorado thunderstorm: Determination of the mean production by cloud‐to‐ground lightning flashes
Authors: Langford A. O. , Portmann R. W. , Daniel J. S. , Miller H. L. , Solomon S.
Published: June 2004

Ground‐based visible absorption spectroscopy of zenith‐scattered sky light was used to measure changes in the column abundance of NO2 during the passage of a thunderstorm over Boulder, Colorado, on September 12, 2002. The measurements showed a 10‐fold rise in slant column NO2 within the thunderstorm cell, consistent with an increase of about 7 ppbv in the lower core updrafts and main precipitation shaft. Mean mixing ratios of about 3 and 1.5 ppbv were inferred for the upper cell and anvil, respectively. These observations, together with measurements from the Denver NEXRAD and the Colorado State University (CSU) CHILL radars, and cloud‐to‐ground (CG) lightning flash data from the National Lightning Detection Network (NLDN), are used to estimate the flash mean production of NOx by CG lightning. The measurements suggest a mean production rate of (5.8 ± 2.9) × 1026 NOx molecules per CG flash, intermediate between the values derived from previous spectroscopic studies and in good agreement with the widely used value of 6.7 × 1026 NOx molecules per CG flash estimated by Price et al. [1997]. This agreement may be fortuitous, however, since the lightning in the present study was about a factor of two less energetic than the mean assumed by Price et al. and the production of (2.3 ± 1.4) × 1017 NOx/J inferred here is significantly larger than the value of 1 × 1017 NOx/J assumed in their calculations. These differences can be reduced, however, if the estimates of Price et al. are recalculated using newer peak current data from the NLDN, and more recently published flash energy production rates of Wang et al. [1998].
Size distributions and mixtures of dust and black carbon aerosol in Asian outflow: Physiochemistry and optical properties
Authors: Clarke A. D. , Shinozuka Y. , Kapustin V. N. , Howell S. , Huebert B. , Doherty S. , Anderson T. , Covert D. , Anderson J. , Hua X. , Moore K. G. , McNaughton C. , Carmichael G. , Weber R.
Published: June 2004

During Transport and Chemical Evolution over the Pacific (TRACE‐P) and Asian Aerosol Characterization Experiment (ACE‐Asia) we measured the dry size distribution of Asian aerosols, their state of mixing, and the optical properties of dust, black carbon (BC) and other aerosol constituents in combustion and/or dust plumes. Optical particle sizing in association with thermal heating extracted volatile components and resolved sizes for dust and refractory soot that usually dominated light absorption. BC was internally mixed with volatile aerosol in ∼85% of accumulation mode particles and constituted ∼5–15% of their mass. These optically effective sizes constrained the soot and dust size distributions and the imaginary part of the dust refractive index, k, to 0.0006 ± 0.0001. This implies a single‐scatter albedo, ϖ (550 nm), for dust ranging from 0.99+ for Dp<1 μm to ∼0.90 at Dp = 10 μm and a size‐integrated campaign average near 0.97 ± 0.01. The typical mass scattering efficiency for the dust was ∼0.3 m2 g−1, and the mass absorption efficiency (MAE) was 0.009 m2 g−1. Less dust south of 25°N and stronger biomass burning signatures resulted in lower values for ϖ of ∼0.82 in plumes aloft. Chemically inferred elemental carbon was moderately correlated with BC light absorption (R2 = 0.40), while refractory soot volume between 0.1 and 0.5 μm was highly correlated (R2 = 0.79) with absorption. However, both approaches yield an MAE for BC mixtures of ∼7 ± 2 m2 g−1 and higher than calculated MAE values for BC of 5 m2 g−1. The increase in the mass fraction of soot and BC in pollution aerosol in the presence of elevated dust appears to be due to uptake of the volatile components onto the coarse dust. This predictably lowered ϖ for the accumulation mode from 0.84 in typical pollution to ∼0.74 in high‐dust events. A chemical transport model revealed good agreement between model and observed BC absorption for most of SE Asia and in biomass plumes but underestimated BC for combustion sources north of 25°N by a factor of ∼3.
Observations of carbon disulfide by differential optical absorption spectroscopy in Shanghai
Authors: Yu Yong , Geyer Andreas , Xie Pinhua , Galle Bo , Chen Limin , Platt Ulrich
Published: June 2004

Carbon disulfide, CS2, is an important sulfur‐containing species in the global environment. Its oxidation to SO2 and COS are basic atmospheric chemical processes in the sulfur cycle. The typical measurement methods for CS2 are gas chromatography with flame photometric detection (GC‐FPD) and gas chromatography ‐ mass spectrometry (GC‐MS). This paper presents CS2 and SO2 long‐term measurements made by the long path Differential Optical Absorption Spectroscopy (DOAS) technique in the winter of 2001 to 2002 in the urban area of Shanghai, China. We found a good correlation between SO2 and CS2 with average [SO2]/[CS2] ≈ 2.1. Combined with an analysis of pollution sources near the measurement site, our measurements indicate that CS2 came mainly from a coal burning furnace close to the measurement site.
Lightning detection with 3‐D discrimination of intracloud and cloud‐to‐ground discharges
Authors: Betz H.‐D. , Schmidt K. , Oettinger P. , Wirz M.
Published: June 2004

A new technique has been developed to operate spatially extended VLF/LF lightning detection networks in a pseudo 3‐D mode in order to facilitate discrimination of intra‐cloud and cloud‐to‐ground lightning. Time‐of‐arrival measurements are carried out with high precision to distinguish VLF/LF‐emission regions of lightning discharges in higher altitudes and near ground, respectively. This is accomplished by utilizing deviations of arrival times measured at sensor stations close to lightning events as compared to arrival times expected on the basis of 2‐D propagation paths. Successful functioning of the method in networks of common dimensions requires that both signal processing and event time tagging is achieved with an accuracy level of about 1 μs. Results are presented from a new network which has been operating continuously since May 2003 and covers southeast Germany in an area of approximately 300 × 400 km. VLF/LF source emission heights of ∼5–15 km have been identified.
Characterization of the temporal sampling error in space‐time‐averaged rainfall estimates from satellites
Authors: Gebremichael Mekonnen , Krajewski Witold F.
Published: June 2004

The authors investigate the sampling error of space‐time‐averaged rain rates due to temporal sampling by satellite, based on 5 years of radar‐based rainfall estimates over the Mississippi River Basin, and use the data to estimate the sampling uncertainty. The two approaches used in this estimation consist of a parametric approach that ignores the diurnal cycle in the rain rate statistics and a nonparametric approach that accounts for it. Results show that the parametric approach yields uncertainty estimates that are generally smaller than those obtained by the nonparametric approach. At a sampling interval of 12 hours, the parametric approach typically underestimates the sampling uncertainty for monthly rainfall by about 28%, 25%, and 14% at averaging areas of 512 × 512 km2, 256 × 256 km2, and 32 × 32 km2, respectively. Results verify the power law scaling characteristics of the sampling uncertainty with respect to the space‐time scales of measurement and the large‐scale precipitation observables suggested by simple models of rain statistics and revealed in previous studies with smaller data sets. With respect to the spatial scale and the mean rain rate, the sampling uncertainty behaves significantly differently from the inverse square‐root behavior predicted by many models. The authors compare the resulting scaling exponents to those obtained from previous studies and identify the factors that need to be addressed in sampling uncertainty comparisons. The main new finding is that the power law exponent governing the dependence of the uncertainty estimate on the mean rain rate appears to exhibit seasonal variations.
Variation in vocalisations of the ground parrot at its northern range
Authors: Chan Ken , Mudie Dianna
Published: June 2004

The eastern ground parrot, Pezoporus wallicus wallicus, is a vulnerable and elusive species whose ecology is little known. We recorded and analysed calls from the northern distributional range of the species. Eleven call types were identified in mainland Queensland, 10 of which were common to three study sites located within Noosa National Park. One call type was absent 50 km to the north in Cooloola National Park, where a call type not heard in Noosa was found instead. There may be less mixing of individuals between Noosa and Cooloola areas than within Noosa. Analysis of sonagrams showed that all calls are structurally simple, and generally lie within a frequency band of 2–6 kHz. There were calls with gradually ascending notes and syllables, and calls with monotone notes within syllables. The Step Ascending call is common to both Noosa and Cooloola, and modifications were detected in Yuraygir National Park and Fraser island. These call types could have derived from the same ancestral call, which may have been modified over time, with isolation maintaining the modified calls within populations. Analysis of call patterns has much potential as a conservation tool in uncommon and elusive birds, but research is required to determine the functions of various call types.
A developmental change in selective attention and global form perception
Authors: Porporino Mafalda , Iarocci Grace , Shore David I. , Burack Jacob A.
Published: June 2004

The primary purpose of the present study was to examine the processing of local and global perception in relation to selective attention during development from childhood to early adulthood. Filtering was the specific component of selective attention that was examined. The influence of varying distractor congruency and compatibility on relative local-global processing was also examined. Distractor congruency and compatibility did not differentially affect local and global processing. With the presence of neutral distractors, however, 6- and 8-year-old participants demonstrated a greater increase in RTs for global targets relative to local targets whereas older children and adults showed the same pattern of RTs for both local and global targets. The results are suggestive of separate developmental trajectories for global and local level processes, with global processing undergoing developmental change at least until 8 years of age.
The indirect link between perceived parenting and adolescent future orientation: A multiple-step model
Authors: Seginer Rachel , Vermulst Ad , Shoyer Shirli
Published: June 2004

The indirect links between perceived mothers’ and fathers’ autonomous-accepting parenting and future orientation were examined in a mediational model consisting of five steps: perceived mothers’ and fathers’ autonomous-accepting parenting, self-evaluation, and the motivational, cognitive representation, and behavioural components of future orientation. Empirical estimates were carried out by LISREL on data collected from 458 (224 girls) Israeli Jewish adolescents (11th graders) regarding two prospective life domains: career and family. These estimates showed a good fit between the theoretical model and four domain-by-gender estimates (girls’ and boys’ career, and girls’ and boys’ family). Similar to recent findings, only few gender differences were found; particularly, girls scored higher on the motivational component applied to career (counter-hypothesis) and on all three components applied to prospective family. Discussion highlighted the pivotal functions of self-evaluation in linking between perceived parenting and the motivational component, and of the motivational component in linking between self-evaluation and the cognitive and behavioural components.
Work environment and smoking cessation over a five-year period
Authors: Albertsen Karen , Hannerz Harald , Borg Vilhelm , Burr Hermann
Published: June 2004

Aims: The authors set out to estimate effects of occupational factors on smoking cessation among Danish employees. Methods: Data from 3,606 observations of smokers gathered from the Danish National Work Environment Cohort Study in 1990, 1995, and 2000 were analysed by logistic regression. The model comprised background variables, smoking variables, and measures of psychosocial and other aspects of the work environment. Results: Statistically significant odds ratios (OR) for cessation were found for medium versus no exposure to noise (OR 0.71, 95% CI 0.54 - 0.93), for high versus low physical workload (OR 0.49, 95% CI 0.47 - 0.73), for high versus low psychological demands (OR 1.42, 95% CI 1.12 - 1.80), and for medium versus low levels of responsibility at work (OR 1.31, 95% CI 1.03 - 1.65). Conclusion: The probability of smoking cessation differs between people with different exposures to certain work environmental factors.
Evidence for Cyclooxygenase‐1 Association with Caveolin‐1 and ‐2 in Cultured Human Embryonic Kidney (HEK 293) Cells
Authors: Cha Seok Ho , Jung Nam‐Hee , Kim Bum‐Rae , Kim Hyun‐Woo , Kwak Jin‐Oh
Published: June 2004

The purpose of this study was to confirm protein‐protein interaction between cyclooxygenase‐1 (COX‐1) and caveolins. The interaction of cyclooxygenase‐1 and caveolins in the cultured human embryonic kidney (HEK 293) cells was investigated using immuno‐precipitation and Western blot analysis. In HEK 293 cells, high levels of caveolin‐2 and low level of caveolin‐1 at mRNA and protein level were observed without any detectable expression of caveolin‐3. Caveolae rich membranous fractions from the HEK 293 cells contained both COX‐1 and caveolin‐1 or caveolin‐2 in same fractions. The experiments of immuno‐precipitation showed complex formation between the COX‐1 and caveolin‐1 or caveolin‐2 in the HEK 293 cells. Confocal microscopic results also support co‐localization of COX‐1 and caveolin‐1 or caveolin‐2 at the plasma membrane. Co‐localization of caveolins with cylooxygenase‐1 in caveolae suggested that caveolin would play an important role in regulating the function of COX‐1.
IUBMB Life, 56: 221‐227, 2004
New Insights into the Regulation of Erythroid Cells
Authors: Ingley Evan , Tilbrook Peta A. , Klinken S Peter
Published: June 2004

The regulation of erythroid cells is complex and occurs at multiple levels. Erythroid precursors, once committed to this lineage, develop in association with specific macrophages within erythroblastic islands. While erythropoietin (Epo) is the principal regulator of erythroid progenitors, other cytokines and nuclear hormones also play an important role in the maturation of these cells. Signalling from the Epo‐receptor activates several pathways, including the JAK/STAT, ras/raf/MAP kinase and PI3 kinase/Akt cascades to promote cell survival, proliferation and differentiation. Transcription factors such as GATA‐1, EKLF and NF‐E2 are crucial for progression along the erythroid maturation pathway; these, and a myriad of other transcription factors, must be expressed at the correct developmental stage for normal red blood cells to be formed.
IUBMB Life, 56: 177‐184, 2004
Alzheimer's Disease Therapeutics: New Approaches to an Ageing Problem
Authors: Small David H. , Losic Dusan , Martin Lisandra L. , Turner Bradley J. , Friedhuber Anna , Aguilar Marie‐Isabel
Published: June 2004

Abnormal proteinaceous deposits are found in the brain of patients with many different neurodegenerative diseases. In many of these diseases, the production of the deposits is probably associated with disease pathogenesis. In Alzheimer's disease (AD), the amyloid protein (Aβ), is produced by the action of enzymes known as secretases, which cleave the β‐amyloid protein precursor. Aβ is secreted from cells in the brain, after which it oligomerizes and is deposited in the extracellular compartment of the brain to form amyloid plaques and amyloid angiopathy. Targeting the production of Aβ and its aggregation is now a key strategy in the development of novel therapeutic agents for the treatment of AD. This review examines the potential of immunization strategies, cholesterol‐lowering drugs, protease inhibitors and nicotinic drugs for the treatment of AD.
IUBMB Life, 56: 203‐208, 2004
The Ubiquitin System: From Basic Mechanisms to the Patient Bed
Authors: Ciechanover Aaron , Iwai Kazuhiro
Published: June 2004

In the ubiquitin system, a target substrate is modified by ubiquitin or a ubiquitin‐like protein. This modification remodels the surface of the target proteins, affecting, among other properties, their stability, interactions with other proteins, activity, and subcellular localization. At least 10 different modifiers have been described in mammalian cells and conjugation of each modifier to its target may result in a different biological effect. In many cases proteins are modified by multiple moieties of ubiquitin that generate a branched polyubiquitin chain. For most proteins, this modification leads to their degradation by the 26S proteasome. Yet, dependent on the character of the internal linkage between the ubiquitin moieties, it can also lead to activation of transcriptional regulators. Modification by a single moiety of ubiquitin can target proteins for degradation in the lysosome/vacuole. Conjugation of ubiquitin or ubiquitin‐like proteins can serve a variety of non‐proteolytic functions, such as activation of enzymes, modulation of membrane dynamics, or routing of the tagged proteins to their sub‐cellular destination. Ubiquitination of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that targets, in a specific manner, thousands of cellular proteins. It is carried out by a modular cascade of enzymes with high specificity towards defined structural motifs in the target proteins. It has emerged as a critically important post‐translational modification that plays major roles in regulating a broad array of basic cellular processes, such as cell division, differentiation, signal transduction, trafficking, and quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases, certain malignancies, neurodegenerative disorders and pathologies of the inflammatory and immune response among them. Understanding of the underlying mechanisms involved is important for the development of novel, mechanism‐based drugs.
IUBMB Life, 56: 193‐201, 2004
Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation
Authors: Arrizabalaga Gustavo , Ruiz Felix , Moreno Silvia , Boothroyd John C.
Published: June 2004

Calcium is a critical mediator of many intracellular processes in eukaryotic cells. In the obligate intracellular parasite Toxoplasma gondii, for example, a rise in [Ca2+] is associated with significant morphological changes and rapid egress from host cells. To understand the mechanisms behind such dramatic effects, we isolated a mutant that is altered in its responses to the Ca2+ ionophore A23187 and found the affected gene encodes a homologue of Na+/H+ exchangers (NHEs) located on the parasite's plasma membrane. We show that in the absence of TgNHE1, Toxoplasma is resistant to ionophore-induced egress and extracellular death and amiloride-induced proton efflux inhibition. In addition, the mutant has increased levels of intracellular Ca2+, which explains its decreased sensitivity to A23187. These results provide direct genetic evidence of a role for NHE1 in Ca2+ homeostasis and important insight into how this ubiquitous pathogen senses and responds to changes in its environment.
Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc, regulating its expression in specific tissues
Authors: Cakouros Dimitrios , Daish Tasman J. , Kumar Sharad
Published: June 2004

The steroid hormone ecdysone regulates moulting, cell death, and differentiation during insect development. Ecdysone mediates its biological effects by either direct activation of gene transcription after binding to its receptor EcR–Usp or via hierarchical transcriptional regulation of several primary transcription factors. In turn, these transcription factors regulate the expression of several downstream genes responsible for specific biological outcomes. DRONC, the Drosophila initiator caspase, is transcriptionally regulated by ecdysone during development. We demonstrate here that the dronc promoter directly binds EcR–Usp. We further show that mutation of the EcR–Usp binding element (EcRBE) reduces transcription of a reporter and abolishes transactivation by an EcR isoform. We demonstrate that EcRBE is required for temporal regulation of dronc expression in response to ecdysone in specific tissues. We also uncover the participation of a putative repressor whose function appears to be coupled with EcR–Usp. These results indicate that direct binding of EcR–Usp is crucial for controlling the timing of dronc expression in specific tissues.
Cellular stresses induce the nuclear accumulation of importin α and cause a conventional nuclear import block
Authors: Miyamoto Yoichi , Saiwaki Takuya , Yamashita Junichi , Yasuda Yoshinari , Kotera Ippei , Shibata Satoshi , Shigeta Masaki , Hiraoka Yasushi , Haraguchi Tokuko , Yoneda Yoshihiro
Published: June 2004

We report here that importin α accumulates reversibly in the nucleus in response to cellular stresses including UV irradiation, oxidative stress, and heat shock. The nuclear accumulation of importin α appears to be triggered by a collapse in the Ran gradient, resulting in the suppression of the nuclear export of importin α. In addition, nuclear retention and the importin β/Ran-independent import of importin α also facilitate its rapid nuclear accumulation. The findings herein show that the classical nuclear import pathway is down-regulated via the removal of importin α from the cytoplasm in response to stress. Moreover, whereas the nuclear accumulation of heat shock cognate 70 is more sensitive to heat shock than the other stresses, importin α is able to accumulate in the nucleus at all the stress conditions tested. These findings suggest that the stress-induced nuclear accumulation of importin α can be involved in a common physiological response to various stress conditions.
Integrin αVβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1
Authors: Annes Justin P. , Chen Yan , Munger John S. , Rifkin Daniel B.
Published: June 2004

Transforming growth factor-βs (TGF-β) are secreted as inactive complexes containing the TGF-β, the TGF-β propeptide, also called the latency-associated protein (LAP), and the latent TGF-β binding protein (LTBP). Extracellular activation of this complex is a critical but incompletely understood step in TGF-β regulation. We have investigated the role of LTBP in modulating TGF-β generation by the integrin αVβ6. We show that even though αvβ6 recognizes an RGD on LAP, LTBP-1 is required for αVβ6-mediated latent TGF-β activation. The domains of LTBP-1 necessary for activation include the TGF-β propeptide-binding domain and a basic amino acid sequence (hinge domain) with ECM targeting properties. Our results demonstrate an LTBP-1 isoform-specific function in αVβ6-mediated latent TGF-β activation; LTBP-3 is unable to substitute for LTBP-1 in this assay. The results reveal a functional role for LTBP-1 in latent TGF-β activation and suggest that activation of specific latent complexes is regulated by distinct mechanisms that may be determined by the LTBP isoform and its potential interaction with the matrix.
Myosin-II reorganization during mitosis is controlled temporally by its dephosphorylation and spatially by Mid1 in fission yeast
Authors: Motegi Fumio , Mishra Mithilesh , Balasubramanian Mohan K. , Mabuchi Issei
Published: June 2004

Cytokinesis in many eukaryotes requires an actomyosin contractile ring. Here, we show that in fission yeast the myosin-II heavy chain Myo2 initially accumulates at the division site via its COOH-terminal 134 amino acids independently of F-actin. The COOH-terminal region can access to the division site at early G2, whereas intact Myo2 does so at early mitosis. Ser1444 in the Myo2 COOH-terminal region is a phosphorylation site that is dephosphorylated during early mitosis. Myo2 S1444A prematurely accumulates at the future division site and promotes formation of an F-actin ring even during interphase. The accumulation of Myo2 requires the anillin homologue Mid1 that functions in proper ring placement. Myo2 interacts with Mid1 in cell lysates, and this interaction is inhibited by an S1444D mutation in Myo2. Our results suggest that dephosphorylation of Myo2 liberates the COOH-terminal region from an intramolecular inhibition. Subsequently, dephosphorylated Myo2 is anchored by Mid1 at the medial cortex and promotes the ring assembly in cooperation with F-actin.
A Multidomain Adhesion Protein Family Expressed inPlasmodium falciparumIs Essential for Transmission to the Mosquito
Authors: Pradel Gabriele , Hayton Karen , Aravind L. , Iyer Lakshminarayan M. , Abrahamsen Mitchell S. , Bonawitz Annemarie , Mejia Cesar , Templeton Thomas J.
Published: June 2004

The recent sequencing of several apicomplexan genomes has provided the opportunity to characterize novel antigens essential for the parasite life cycle that might lead to the development of new diagnostic and therapeutic markers. Here we have screened the Plasmodium falciparum genome sequence for genes encoding extracellular multidomain putative adhesive proteins. Three of these identified genes, named PfCCp1, PfCCp2, and PfCCp3, have multiple adhesive modules including a common Limulus coagulation factor C domain also found in two additional Plasmodium genes. Orthologues were identified in the Cryptosporidium parvum genome sequence, indicating an evolutionary conserved function. Transcript and protein expression analysis shows sexual stage–specific expression of PfCCp1, PfCCp2, and PfCCp3, and cellular localization studies revealed plasma membrane–associated expression in mature gametocytes. During gametogenesis, PfCCps are released and localize surrounding complexes of newly emerged microgametes and macrogametes. PfCCp expression markedly decreased after formation of zygotes. To begin to address PfCCp function, the PfCCp2 and PfCCp3 gene loci were disrupted by homologous recombination, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition. Our results describe members of a conserved apicomplexan protein family expressed in sexual stage Plasmodium parasites that may represent candidates for subunits of a transmission-blocking vaccine.
Ubiquitin-dependent Degradation of p73 Is Inhibited by PML
Authors: Bernassola Francesca , Salomoni Paolo , Oberst Andrew , Di Como Charles J. , Pagano Michele , Melino Gerry , Pandolfi Pier Paolo
Published: June 2004

p73 has been identified recently as a structural and functional homologue of the tumor suppressor p53. Here, we report that p73 stability is directly regulated by the ubiquitin–proteasome pathway. Furthermore, we show that the promyelocytic leukemia (PML) protein modulates p73 half-life by inhibiting its degradation in a PML–nuclear body (NB)–dependent manner. p38 mitogen-activated protein kinase–mediated phosphorylation of p73 is required for p73 recruitment into the PML-NB and subsequent PML-dependent p73 stabilization. We find that p300-mediated acetylation of p73 protects it against ubiquitinylation and that PML regulates p73 stability by positively modulating its acetylation levels. As a result, PML potentiates p73 transcriptional and proapoptotic activities that are markedly impaired in Pml−/− primary cells. Our findings demonstrate that PML plays a crucial role in modulating p73 function, thus providing further insights on the molecular network for tumor suppression.
Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells
Authors: Akdis Mübeccel , Verhagen Johan , Taylor Alison , Karamloo Fariba , Karagiannidis Christian , Crameri Reto , Thunberg Sarah , Deniz Günnur , Valenta Rudolf , Fiebig Helmut , Kegel Christian , Disch Rainer , Schmidt-Weber Carsten B. , Blaser Kurt , Akdis Cezmi A.
Published: June 2004

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.