bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary State Formation in Mesoamerica
Authors: Spencer Charles S. , Redmond Elsa M.
Published: December 2004

▪ Abstract  In this review, we examine the earliest states in Mesoamerica and how they developed. We present a definition of the state and explain why first-generation or primary states have special significance in anthropology and archaeology; we also discuss how anthropological archaeologists can detect the emergence of state organization in the archaeological record. We review the archaeological data bearing on early state formation in Oaxaca, the Southern Gulf Coast, the Southeastern Lowlands, and the Basin of Mexico. Although we acknowledge that more data are needed from all regions, we conclude that Oaxaca currently provides the most compelling evidence of primary state formation in Mesoamerica.
The Evolution of Human Skin and Skin Color
Authors: Jablonski Nina G.
Published: December 2004

▪ Abstract  Humans skin is the most visible aspect of the human phenotype. It is distinguished mainly by its naked appearance, greatly enhanced abilities to dissipate body heat through sweating, and the great range of genetically determined skin colors present within a single species. Many aspects of the evolution of human skin and skin color can be reconstructed using comparative anatomy, physiology, and genomics. Enhancement of thermal sweating was a key innovation in human evolution that allowed maintenance of homeostasis (including constant brain temperature) during sustained physical activity in hot environments. Dark skin evolved pari passu with the loss of body hair and was the original state for the genus Homo. Melanin pigmentation is adaptive and has been maintained by natural selection. Because of its evolutionary lability, skin color phenotype is useless as a unique marker of genetic identity. In recent prehistory, humans became adept at protecting themselves from the environment through clothing and shelter, thus reducing the scope for the action of natural selection on human skin.
Water Use
Authors: Gleick Peter H.
Published: December 2004

Water managers and planners are slowly beginning to change their perspective and perceptions about how best to meet human needs for water; they are shifting from a focus on building supply infrastructure to improving their understanding of how water is used and how those uses can best be met. This review discusses definitions of water use, explores the history of water use around the world and in characteristic regions, identifies problems with collecting and analyzing water data, and addresses the question of improving water-use efficiency and productivity in different regions and economic sectors. There is growing interest on the part of water managers around the world to implement these approaches to lessen pressures on increasingly scarce water resources, reduce the adverse ecological effects of human withdrawals of water, and improve long-term sustainable water use.
D0-bar D0 Mixing and Rare Charm Decays
Authors: Burdman Gustavo , Shipsey Ian
Published: December 2004

We review the current status of flavor-changing neutral currents in the charm sector. We focus on the standard-model predictions and identify the main sources of theoretical uncertainties in both [Formula: see text] mixing and rare charm decays. The potential of these observables for constraining short-distance physics in the standard model and its extensions is compromised by the presence of large nonperturbative effects. We examine the possible discovery windows in which short-distance physics can be tested and study the effects of various extensions to the standard model. The current experimental situation and future prospects are reviewed.
OBSERVATION OF THE TAU NEUTRINO
Authors: Lundberg B. , Niwa K. , Paolone V.
Published: December 2004

▪ Abstract  The τ neutrino was the last standard-model fermion to be directly observed. We report on the strategy, design, and results of the DONuT experiment. The data were acquired at Fermilab during 1997, and in July 2000, the DONuT collaboration presented four τ-neutrino interactions. Modern nuclear-emulsion processing was the key technology that made it possible to detect the decay of τ leptons produced in charged-current interactions of τ neutrinos. The precision of the emulsion data and the speed of digitization enabled the use of novel methods to locate interaction vertices and search for decays in emulsion data. We also discuss the level of background in the τ signal, which is small enough to permit the identification of individual τ events with high confidence.
LATTICE QCD AT FINITE TEMPERATURE
Authors: Laermann E. , Philipsen O.
Published: December 2004

▪ Abstract  We review lattice QCD investigations at high temperature. After a short introduction to thermal QCD on the lattice, we report on the present understanding of the phase diagram and the equation of state, particularly in the presence of dynamical quarks. We discuss various screening lengths in the plasma phase, including results from dimensionally reduced QCD. We then summarize lattice data on quark-number susceptibilities and spectral densities, both of which are immediately relevant to the interpretation of heavy-ion experiments. A major section is devoted to simulations of QCD at small, yet phenomenologically important, values for the baryon density.
Exploring directionality in spontaneous heart period and systolic pressure variability interactions in humans: implications in the evaluation of baroreflex gain
Authors: Nollo Giandomenico , Faes Luca , Porta Alberto , Antolini Renzo , Ravelli Flavia
Published: December 2004

Although in physiological conditions RR interval and systolic arterial pressure (SAP) are likely to interact in a closed loop, the traditional cross-spectral analysis cannot distinguish feedback (FB) from feedforward (FF) influences. In this study, a causal approach was applied for calculating the coherence from SAP to RR ( Ks-r) and from RR to SAP ( Kr-s) and the gain and phase of the baroreflex transfer function. The method was applied, compared with the noncausal one, to RR and SAP series taken from 15 healthy young subjects in the supine position and after passive head-up tilt. For the low frequency (0.04–0.15 Hz) spectral component, the enhanced FF coupling ( Kr-s = 0.59 ± 0.21, significant in 14 subjects) and the blunted FB coupling ( Ks-r = 0.17 ± 0.17, significant in 4 subjects) found at rest indicated the prevalence of nonbaroreflex mechanisms. The tilt maneuver recovered FB influences ( Ks-r = 0.47 ± 0.16, significant in 14 subjects), which were stronger than FF interactions ( Ks-r = 0.34 ± 0.19, significant in 9 subjects). At the respiratory frequency, the RR-SAP regulation was balanced at rest ( Ks-r = 0.30 ± 0.18 and Kr-s = 0.29 ± 0.20, significant in 11 and 8 subjects) and shifted toward FB mechanisms after tilt ( Ks-r = 0.35 ± 0.19 and Kr-s = 0.19 ± 0.11, significant in 14 and 8 subjects). The causal baroreflex gain estimates were always lower than the corresponding noncausal values and decreased significantly from rest to tilt in both frequency bands. The tilt-induced increase of the phase lag from SAP to RR suggested a shift from vagal to sympathetic modulation. Thus the importance of nonbaroreflex interactions pointed out the necessity of accounting for causality in the cross-spectral analysis of the interactions between cardiovascular variables in healthy humans.
A ventricular-vascular coupling model in presence of aortic stenosis
Authors: Garcia Damien , Barenbrug Paul J. C. , Pibarot Philippe , Dekker André L. A. J. , van der Veen Frederik H. , Maessen Jos G. , Dumesnil Jean G. , Durand Louis-Gilles
Published: December 2004

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V3) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V3 model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99 x − 2.36 with a coefficient of determination r2 = 0.98. There was also very good agreement between estimated and measured stroke volumes ( y = 1.03 x + 2.2, r2 = 0.96, SEE = 2.8 ml). Hence, this mathematical V3 model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.
Prostacyclin attenuates oxidative damage of myocytes by opening mitochondrial ATP-sensitive K+ channels via the EP3 receptor
Authors: Shinmura Ken , Tamaki Kayoko , Sato Toshiaki , Ishida Hideyuki , Bolli Roberto
Published: December 2004

Prostacyclin (PGI2) and the PGE family alleviate myocardial ischemia-reperfusion injury and limit oxidative damage. The cardioprotective effects of PGI2 have been traditionally ascribed to activation of IP receptors. Recent advances in prostanoid research have revealed that PGI2 can bind not only to IP, but also to EP, receptors, suggesting cross talk between PGI2 and PGEs. The mechanism(s) whereby PGI2 protects myocytes from oxidative damage and the specific receptors involved remain unknown. Thus fresh isolated adult rat myocytes were exposed to 200 μM H2O2 with or without carbaprostacyclin (cPGI2), IP-selective agonists, and ONO-AE-248 (an EP3-selective agonist). Cell viability was assessed by trypan blue exclusion after 30 min of H2O2 superfusion. cPGI2 and ONO-AE-248 significantly improved cell survival during H2O2 superfusion; IP-selective agonists did not. The protective effect of cPGI2 and ONO-AE-248 was completely abrogated by pretreatment with 5-hydroxydecanoate or glibenclamide. In the second series of experiments, the mitochondrial ATP-sensitive K+ (KATP) channel opener diazoxide (Dx) reversibly oxidized flavoproteins in control myocytes. Exposure to prostanoid analogs alone had no effect on flavoprotein fluorescence. A second application of Dx in the presence of cPGI2 or ONO-AE-248 significantly increased flavoprotein fluorescence compared with Dx alone, but IP-selective agonists did not. This study demonstrates that PGI2 analogs protect cardiac myocytes from oxidative stress mainly via activation of EP3. The data also indicate that activation of EP3 receptors primes the opening of mitochondrial KATP channels and that this mechanism is essential for EP3-dependent protection.
Medullary lateral tegmental field: control of respiratory rate and vagal lung inflation afferent influences on sympathetic nerve discharge
Authors: Phillips Shaun W. , Gebber Gerard L. , Barman Susan M.
Published: December 2004

We used spectral analysis and event-triggered averaging to determine the effects of chemical inactivation of the medullary lateral tegmental field (LTF) on 1) the relationship of intratracheal pressure (ITP, an index of vagal lung inflation afferent activity) to sympathetic nerve discharge (SND) and phrenic nerve activity (PNA) and 2) central respiratory rate in paralyzed, artificially ventilated dial-urethane-anesthetized cats. ITP-SND coherence value at the frequency of artificial ventilation was significantly ( P < 0.05; n = 18) reduced from 0.73 ± 0.04 (mean ± SE) to 0.24 ± 0.04 after bilateral microinjection of muscimol into the LTF. Central respiratory rate was unexpectedly increased in 12 of these experiments (0.28 ± 0.03 vs. 0.95 ± 0.25 Hz). The ITP-PNA coherence value was variably affected by chemical inactivation of the LTF. It was unchanged when central respiratory rate was also not altered, decreased when respiratory rate was increased above the rate of artificial ventilation, and increased when respiratory rate was raised from a value below the rate of artificial ventilation to the same frequency as the ventilator. Chemical inactivation of the LTF increased central respiratory rate in four of six vagotomized cats but did not significantly affect the PNA-SND coherence value. These data demonstrate that the LTF 1) plays a critical role in mediating the effects of vagal lung inflation afferents on SND but not PNA, 2) helps maintain central respiratory rate in the physiological range, but 3) is not involved in the coupling of central respiratory and sympathetic circuits.
Posterior Urethral Valves: Prenatal Diagnostic Signs and Outcome
Authors: Eckoldt Felicitas , Heling K.S. , Woderich R. , Wolke S.
Published: December 2004

Introduction: Urethral valves can be of enormous clinical importance. Both the prognosis for an affected fetus and the indication for a prenatal therapeutic intervention depend to a high degree on the accuracy of the prenatal diagnosis. Patients and Methods: The sonographic findings and the results of the postnatal diagnostic workup of 24 boys treated for urethral valves in our institute are analyzed in the present paper. Results: Out of a group of 900 children, diagnosed prenatally as having urinary tract anomalies, the postnatal diagnostic workup revealed 24 boys suffering from posterior urethral valves. The combination of megacystis, oligohydramnios, and bilateral renal abnormalities was present in 3 boys, and it was only in these cases that urethral valves were correctly identified as the underlying pathology. The largest group (n = 16) of these fetuses presented with bilateral hydronephrosis with and without megaureter. Megacystis in any combination with other findings was detected only in 4 patients. Oligohydramnios as a sign of impaired renal function was observed in four pregnancies. Four children suffered postnatally from beginning renal insufficiency. Eight infants (33%) required some form of respiratory support. This group included the 4 newborns with oligohydramnios during the pregnancy. Conclusions: Posterior urethral valves represent a rare but severe congenital malformation. They can disrupt the development of the entire urinary tract and may be life-limiting to the affected boy. Only rarely, however, are they manifested as the complete pathological picture on prenatal ultrasound. In most cases, bilateral impairment of the fetal renal development suggests severe subvesical obstruction. Thus in cases with bilateral renal impairment on prenatal ultrasonography, posterior urethral valves are to be excluded postnatally. Oligohydramnios is a predictor of a poor outcome of the renal function.
Topical Application of Ionic Polymers Affects Skin Permeability Barrier Homeostasis
Authors: Denda M. , Nakanishi K. , Kumazawa N.
Published: December 2004

We previously demonstrated that the external electric potential affected skin barrier homeostasis. On the other hand, topical application of an ionic polymer formed a diffusion electric double layer on the surface of the skin. Thus, we evaluated effects of topical application of ionic polymers on the damaged skin barrier. Application of a nonionic polymer did not affect barrier recovery. Application of sodium salts of anionic polymers accelerated barrier recovery, while that of cationic polymers delayed it. Topical application of a sodium-exchange resin accelerated barrier recovery, but application of a calcium-exchange resin had no effect even when the resins had the same structure. Application of a chloride-exchange resin delayed barrier recovery. Topical application of ionic polymers influenced skin barrier homeostasis.
Expression Analysis of the SG-SSPN Complex in Smooth Muscle and Endothelial Cells of Human Umbilical Cord Vessels
Authors: Ramírez-Sánchez I. , Rosas-Vargas H. , Ceballos-Reyes G. , Salamanca F. , Coral-Vázquez R.M.
Published: December 2004

Recently, participation of the sarcoglycan (SG)-sarcospan (SSPN) complex in the development of cardiomyopathy in patients with limb-girdle muscular dystrophy has been shown, and presence of the complex in smooth muscle may be important for the contraction/dilation process of vessels. However, there are few studies determining the SG-SSPN complex in vascular smooth muscle and endothelial cells of vessels. In this study, we analyzed by reverse transcriptase-polymerase chain reaction and immunofluorescence the expression of different components of the complex in vein/artery smooth muscle and endothelial cells of the human umbilical cord. By RNA analysis, we observed expression of α-, β-, γ-, δ-, Ε-SG, and SSPN in smooth muscle cells. In endothelial cells, RNA expression was restricted to β-, δ-, Ε-SG, and SSPN. At protein level, we observed in smooth muscle the presence of β-, δ-, Ε-SG, and SSPN. In endothelial cells, immunostaining only evidenced the presence of Ε-SG and SSPN. However, colocalization of SGs and SSPN with dystrophin and utrophin was noted. These results, interestingly, suggest that the SG-SSPN complex may either form with dystrophin or utrophin in smooth muscle cells, and with utrophin in endothelial cells. Additionally, we also observed in some smooth muscle regions the colocalization of the SG-SSPN complex with caveolin, with colocalization being more pronounced between Ε-SG-SSPN and caveolin in endothelial cells.
The Molecular Basis for Abnormal Human Lung Development
Authors: Groenman Frederick , Unger Sharon , Post Martin
Published: December 2004

Our understanding of lung development in the past two decades has moved from an anatomical to a histological basis and, most recently, to a molecular basis. Tissue interactions specify tracheal and lung primordia formation, program branching morphogenesis of the airway epithelium and regulate epithelial differentiation. In addition, lung development is influenced by mechanical and humoral factors. The regulatory molecules involved in morphogenetic signaling include growth and transcription factors and extracellular matrix molecules. These morphogenetic signals are responsible for lung patterning and differentiation. We will provide a brief overview of molecular signaling during early respiratory formation, airway branching, pulmonary vascularization and epithelial differentiation. We will then review aberrant morphogenetic signaling in human lung abnormalities, such as tracheoesophageal fistula, congenital diaphragmatic hernia, pulmonary hyperplasia, alveolar capillary dysplasia, congenital cystic adenomatoid malformation and bronchopulmonary dysplasia.
Cytomegalovirus Enteritis in an Immunocompetent Host
Authors: Petrogiannopoulos Constantinos L. , Kalogeropoulos Sotirios G. , Dandakis Dimitrios C. , Hartzoulakis Georgios A. , Karahalios George N. , Flevaris Christos P. , Zacharof Antonios K.
Published: December 2004

A 60-year-old healthy woman presented with fever, abdominal pain and bloody diarrhea. After initial conservative therapy, enterectomy was performed because of perforation of the jejunum. Histological analysis and high titer of anti-CMV IgM confirmed the diagnosis. A 2-year follow-up was uneventful. CMV enterocolitis is frequent in immunocompromised patients, but rare in immunocompetent subjects.
In vitro Measurement of the Time-Related Efficacy of Gentamicin Sulfate Release from Bone Cements
Authors: Bálint Lehel , Kocsis Béla , Szántó Zalán , Szabó György
Published: December 2004

Background: The aim of the present study was to establish an in vitro microbiologic monitoring system which measures the dynamics of antibiotic release from acrylic bone cement and its antibacterial efficacy. Methods: Palacos R® and Orthofix R® cements containing gentamicin sulfate were tested. The in vitro elution dynamics was analyzed by plate diffusion method during a 1-year period after mixing. High but rapidly decreasing antibiotic levels were detected within the 1st week, resulting in an almost steadily low concentration by the end of the 1st month. After 1 year, it was still possible to demonstrate the inhibitory effect of the drug from both cements. Comparison of the time-related release between the antibiotics failed to find any statistically significant differences. Conclusion: The method described is a useful and reproducible technique for the in vitro measurement of the inhibitory activity of antibiotic released from bone cements.
Cytokine-Stimulated GTP Cyclohydrolase I Expression in Endothelial Cells Requires Coordinated Activation of Nuclear Factor-κB and Stat1/Stat3
Authors: Huang Annong , Zhang Ying-Yi , Chen Kai , Hatakeyama Kazuyuki , Keaney John F.
Published: December 2004

Endothelial production of nitric oxide (NO) is dependent on adequate cellular levels of tetrahydrobiopterin (BH
4
), an important cofactor for the nitric oxide synthases. Vascular diseases are often characterized by vessel wall inflammation and cytokine treatment of endothelial cells increases BH
4
levels, in part through the induction of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for BH
4
biosynthesis. However, the molecular mechanisms of cytokine-mediated GTPCH I induction in the endothelium are not entirely clear. We sought to investigate the signaling pathways whereby cytokines induce GTPCH I expression in human umbilical vein endothelial cells (HUVECs). Interferon-γ (IFN-γ) induced endothelial cell GTPCH I protein and BH
4
modestly, whereas high-level induction required combinations of IFN-γ and tumor necrosis factor-α (TNF-α). In the presence of IFN-γ, TNF-α increased GTPCH I mRNA in a manner dependent on nuclear factor-κB (NF-κB), as this effect was abrogated by overexpression of a dominant-negative IκB construct. HUVEC IFN-γ treatment resulted in signal transducer and activator of transcription 1 (Stat1) activation and DNA binding in a Jak2-dependent manner, as this was inhibited by AG490. Conversely, overexpression of Jak2 effectively substituted for IFN-γ in supporting TNF-α–mediated GTPCH I induction. The role of IFN-γ was also Stat1-dependent as Stat1-null cells exhibited no GTPCH I induction in response to cytokines. However, Stat1 activation with oncostatin M failed to support TNF-α–mediated GTPCH I induction because of concomitant Stat3 activation. Consistent with this notion, siRNA-mediated Stat3 gene silencing allowed oncostatin M to substitute for IFN-γ in this system. These data implicate both NF-κB and Stat1 in endothelial cell cytokine-stimulated GTPCH I induction and highlight the role of Stat3 in modulating Stat1-supported gene transcription. Thus, IFN-γ and TNF-α exert distinct but cooperative roles for BH
4
biosynthesis in endothelium that may have important implications for vascular function during vascular inflammation.
Outdoor Air Pollution and Stroke in Sheffield, United Kingdom
Authors: Maheswaran Ravi , Haining Robert P. , Brindley Paul , Law Jane , Pearson Tim , Fryers Peter R. , Wise Stephen , Campbell Michael J.
Published: December 2004

Background and Purpose—

Current evidence suggests that stroke mortality and hospital admissions should be higher in areas with elevated levels of outdoor air pollution because of the combined acute and chronic exposure effects of air pollution. We examined this hypothesis using a small-area level ecological correlation study.

Methods—

We used 1030 census enumeration districts as the unit of analysis and examined stroke deaths and hospital admissions from 1994 to 1998, with census denominator counts for people ≥45 years. Modeled air pollution data for particulate matter (PM
10
), nitrogen oxides (NO
x
), and carbon monoxide (CO) were interpolated to census enumeration districts. We adjusted for age, sex, socioeconomic deprivation, and smoking prevalence.

Results—

The analysis was based on 2979 deaths, 5122 admissions, and a population of 199 682. After adjustment for potential confounders, stroke mortality was 37% (95% CI, 19 to 57), 33% (95% CI, 14 to 56), and 26% (95% CI, 10 to 46) higher in the highest, relative to the lowest, NO
x
, PM
10
, and CO quintile categories, respectively. Corresponding increases in risk for admissions were 13% (95% CI, 1 to 27), 13% (95% CI, −1 to 29), and 11% (95% CI, −1 to 25).

Conclusion—

The results are consistent with an excess risk of stroke mortality and, to a lesser extent, hospital admissions in areas with high outdoor air pollution levels. If causality were assumed, 11% of stroke deaths would have been attributable to outdoor air pollution. Targeting policy interventions at high pollution areas may be a feasible option for stroke prevention.
Seasonal and Diurnal Fluxes of Radiation, Heat, Water Vapor, and Carbon Dioxide over a Suburban Area
Authors: Moriwaki R. , Kanda M.
Published: December 2004

Based on 1 yr of field measurements, the diurnal, seasonal, and annual fluxes of energy and carbon dioxide (CO2) at a residential area of Tokyo, Japan, are described. The major findings are as follows. 1) The storage heat flux G in the daytime had little seasonal variation, irrespective of significant seasonal change of net all-wave radiation Rn. 2) The latent heat flux in the summer daytime was large despite the small areal fraction of natural coverage (trees and bare soil). The estimated local latent heat flux per unit natural coverage was 2 times the available energy (Rn − G), which indicates that the “oasis effect” was significant. 3) The CO2 flux was always upward throughout the year and the magnitude was larger in winter, mainly because of an increase of fossil fuel consumption. The annual total CO2 flux was 6 times the downward CO2 flux at a typical temperate deciduous forest.
Comparison of Vertical Soundings and Sidewall Air Temperature Measurements in a Small Alpine Basin
Authors: Whiteman C. David , Eisenbach Stefan , Pospichal Bernhard , Steinacker Reinhold
Published: December 2004

Tethered balloon soundings from two sites on the floor of a 1-km-diameter limestone sinkhole in the eastern Alps are compared with pseudovertical temperature “soundings” from three lines of temperature dataloggers on the basin's northwest, southwest, and southeast sidewalls. Under stable nighttime conditions with low background winds, the pseudovertical profiles from all three lines were good proxies for free air temperature soundings over the basin center, with a mean nighttime cold temperature bias of about 0.4°C and a standard deviation of 0.4°C. Cold biases were highest in the upper basin where relatively warm air subsides to replace air that spills out of the basin through the lowest-altitude saddle. On a windy night, standard deviations increased to 1°–2°C. After sunrise, the varying exposures of the dataloggers to sunlight made the pseudovertical profiles less useful as proxies for free air soundings. The good correspondence between sidewall and free air temperatures during high-static-stability conditions suggests that sidewall soundings can be used to monitor temperatures, temperature gradients, and temperature inversion evolution in the sinkhole. Sidewall soundings can produce more frequent profiles at lower cost than can tethersondes or rawinsondes, and extension of these findings to other enclosed or semienclosed topographies may enhance future basic meteorological research or support applications studies in agriculture, forestry, air pollution, and land use planning.
Evaluation of MM5 High-Resolution Real-Time Forecasts over the Urban Area of Athens, Greece
Authors: Kotroni V. , Lagouvardos K.
Published: December 2004

In this paper the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) forecast skill over an area of complex terrain is evaluated. Namely, the model is verified over a period of 1 yr (2002) over the greater area of Athens, Greece, for its near-surface temperature and wind forecasts, at 8- and 2-km grid spacing, but also over a 15-day period for the summer thunderstorm activity forecasts. For the near-surface temperature a cold bias is evident. The model is, in general, unable to reproduce the summer heat waves observed in the area. The increase of the grid resolution, from 8 to 2 km, results in an improvement of the forecast skill. Postprocessing of the forecasts by applying a Kalman-filtering correction method was very effective for both the 8- and the 2-km forecasts. For the forecast skill of wind, the analysis showed that there is not any net increase of the errors with increasing forecast time for the 48-h forecast period, the mean absolute errors, in general, present the lowest values at noontime, and the increase in resolution, from 8 to 2 km, results in a slight decrease of these errors. The analysis of the model skill to accurately forecast summertime precipitation showed that the 2-km simulations, without activation of the convective parameterization scheme, were unable to reproduce the observed thunderstorm activity. Sensitivity tests for the same period with simulations in which the convective parameterization was not activated for both the 8- and the 2-km simulations were still inaccurate, while activation of the convective parameterization scheme at all grids (even at 2 km) considerably increased the precipitation forecast skill.
Detection of apoptosis by caspase-3 activation in tracheal aspirate neutrophils from premature infants: relationship with NF-κB activation
Authors: Cheah Fook-Choe , Hampton Mark B , Darlow Brian A , Winterbourn Christine C , Vissers Margret C M
Published: December 2004

In premature infants, inflammatory conditions in the lungs may result in the development of chronic lung disease. As neutrophil apoptosis is important for the resolution of inflammation and prevention of tissue injury, we set out to determine the extent of neutrophil apoptosis in tracheal aspirate samples from premature infants. Activation of the transcription factor nuclear factor (NF)-κB, which causes a delay in neutrophil apoptosis, was also investigated. We obtained 68 tracheal aspirate samples from 27 infants with median gestation and birthweight of 26 weeks and 860 g, respectively. Apoptosis was assessed by immunofluorescent detection of the active form of caspase-3, this assay being validated with peripheral blood neutrophils. Activation of NF-κB was monitored by the nuclear translocation of the p65 subunit, detected by immunofluorescence. Cleaved caspase-3 was detected in 11 of the 68 samples, and a median of 40% of the neutrophils showed activated caspase-3 (range 3–92%). A majority of the samples did not show evidence of apoptosis. Caspase activation was seen in cells with multilobed nuclear morphology, suggesting that early apoptosis was detectable. There was no significant difference in respiratory outcomes between infants with or without neutrophil apoptosis. Seventeen of the 68 samples (25%) had evidence of activated NF-κB, and a median of 20% (range 6–41%) of neutrophils showed activation. In all but one tracheal aspirate sample, there was a mutually exclusive relationship between activated caspase-3 and NF-κB activation, which supports in vitro observations that NF-κB activation delays neutrophil apoptosis.
Gene Expression Profiling of Leiomyoma and Myometrial Smooth Muscle Cells in Response to Transforming Growth Factor-β
Authors: Luo Xiaoping , Ding Li , Xu Jingxia , Chegini Nasser
Published: December 2004

Altered expression of the TGF-β system is recognized to play a central role in various fibrotic disorders, including leiomyoma. In this study we performed microarray analysis to characterize the gene expression profile of leiomyoma and matched myometrial smooth muscle cells (LSMC and MSMC, respectively) in response to the time-dependent action of TGF-β and, after pretreatment with TGF-β type II receptor (TGF-βRII) antisense oligomer-blocking/reducing TGF-β autocrine/paracrine actions. Unsupervised and supervised assessments of the gene expression values with a false discovery rate selected at P ≤ 0.001 identified 310 genes as differentially expressed and regulated in LSMC and MSMC in a cell- and time-dependent manner by TGF-β. Pretreatment with TGF-βRII antisense resulted in changes in the expression of many of the 310 genes regulated by TGF-β, with 54 genes displaying a response to TGF-β treatment. Comparative analysis of the gene expression profile in TGF-βRII antisense- and GnRH analog-treated cells indicated that these treatments target the expression of 222 genes in a cell-specific manner. Gene ontology assigned these genes functions as cell cycle regulators, transcription factors, signal transducers, tissue turnover, and apoptosis. We validated the expression and TGF-β time-dependent regulation of IL-11, TGF-β-induced factor, TGF-β-inducible early gene response, early growth response 3, CITED2 (cAMP response element binding protein-binding protein/p300-interacting transactivator with ED-rich tail), Nur77, Runx1, Runx2, p27, p57, growth arrest-specific 1, and G protein-coupled receptor kinase 5 in LSMC and MSMC using real-time PCR. Together, the results provide the first comprehensive assessment of the LSMC and MSMC molecular environment targeted by autocrine/paracrine action of TGF-β, highlighting potential involvement of specific genes whose products may influence the outcome of leiomyoma growth and fibrotic characteristics by regulating inflammatory response, cell growth, apoptosis, and tissue remodeling.
Minireview: Transcriptional Regulation in Pancreatic Development
Authors: Habener Joel F. , Kemp Daniel M. , Thomas Melissa K.
Published: December 2004

Considerable progress has been made in the understanding of the sequential activation of signal transduction pathways and the expression of transcription factors during pancreas development. Much of this understanding has been obtained by analyses of the phenotypes of mice in which the expression of key genes has been disrupted (knockout mice). Knockout of the genes for Pdx1, Hlxb9, Isl1, or Hex results in an arrest of pancreas development at a very early stage (embryonic d 8–9). Disruption of genes encoding components of the Notch signaling pathway, e.g. Hes1 or neurogenin-3, abrogates development of the endocrine pancreas (islets of Langerhans). Disruption of transcription factor genes expressed more downstream in the developmental cascade (Beta2/NeuroD, Pax4, NKx2.2, and Nkx6.1) curtails the formation of insulin-producing β-cells. An understanding of the importance of transcription factor genes during pancreas development has provided insights into the pathogenesis of diabetes, in which the mass of insulin-producing β-cells is reduced.
Relaxin Stimulates Protein Kinase C ζ Translocation: Requirement for Cyclic Adenosine 3′,5′-Monophosphate Production
Authors: Nguyen Bao T. , Dessauer Carmen W.
Published: December 2004

Relaxin is a polypeptide hormone that activates the leucine-rich repeat containing G protein-coupled receptors, LGR7 and LGR8. In an earlier study, we reported that relaxin produces a biphasic time course and the second wave of cAMP is highly sensitive to phosphoinositide-3 kinase inhibitors (LY294002 and wortmannin). LY294002 inhibits relaxin-mediated increases in cAMP production by 40–50% across a large range of relaxin concentrations. Here we show that protein kinase C ζ (PKCζ) is a component of relaxin signaling in THP-1 cells. Sphingomyelinase increases cAMP production due to the release of ceramide, a direct activator of PKCζ. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin induced cAMP production to the same degree (∼40%) as LY294002. Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, pregnant human myometrial 1–31, and mouse mesangial cells, as shown by immunocytochemistry. PKCζ translocation is phosphoinositide-3 kinase dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared with mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. In summary, we present a novel role for PKCζ in relaxin-mediated stimulation of cAMP.
Zebrafishpax8is required for otic placode induction and plays a redundant role with Pax2 genes in the maintenance of the otic placode
Authors: Mackereth Melinda D. , Kwak Su-Jin , Fritz Andreas , Riley Bruce B.
Published: December 2004

Vertebrate Pax2 and Pax8 proteins are closely related transcription factors hypothesized to regulate early aspects of inner ear development. In zebrafish and mouse, Pax8 expression is the earliest known marker of otic induction, and Pax2 homologs are expressed at slightly later stages of placodal development. Analysis of compound mutants has not been reported. To facilitate analysis of zebrafish pax8, we completed sequencing of the entire gene, including the 5′ and 3′ UTRs. pax8transcripts undergo complex alternative splicing to generate at least ten distinct isoforms. Two different subclasses of pax8 splice isoforms encode different translation initiation sites. Antisense morpholinos (MOs)were designed to block translation from both start sites, and four additional MOs were designed to target different exon-intron boundaries to block splicing. Injection of MOs, individually and in various combinations,generated similar phenotypes. Otic induction was impaired, and otic vesicles were small. Regional ear markers were expressed correctly, but hair cell production was significantly reduced. This phenotype was strongly enhanced by simultaneously disrupting either of the co-inducers fgf3 or fgf8, or another early regulator, dlx3b, which is thought to act in a parallel pathway. In contrast, the phenotype caused by disrupting foxi1, which is required for pax8 expression, was not enhanced by simultaneously disrupting pax8. Disrupting pax8,pax2a and pax2b did not further impair otic induction relative to loss of pax8 alone. However, the amount of otic tissue gradually decreased in pax8-pax2a-pax2b-deficient embryos such that no otic tissue was detectable by 24 hours post-fertilization. Loss of otic tissue did not correlate with increased cell death, suggesting that otic cells dedifferentiate or redifferentiate as other cell type(s). These data show that pax8 is initially required for normal otic induction, and subsequently pax8, pax2a and pax2b act redundantly to maintain otic fate.
Multi‐level temporal abstraction for medical scenario construction
Authors: Silvent Anne‐Sophie , Dojat Michel , Garbay Catherine
Published: December 2004

The automatic recognition of typical pattern sequences (scenarios), as they are developing, is of crucial importance for computer‐aided patient supervision. However, the construction of such scenarios directly from medical expertise is unrealistic in practice. In this paper, we present a methodology for data abstraction and for the extraction of specific events (data mining) to eventually construct such scenarios. Data abstraction and data mining are based on the management of three key concepts, data, information and knowledge, which are instantiated via an ontology specific of our medical domain application. After a detailed description of the proposed methodology, we apply it to the supervision of patients hospitalized in intensive care units. We report the results obtained for the extraction of typical abstracted pattern sequences during the process of weaning from mechanical ventilation. Copyright © 2004 John Wiley & Sons, Ltd.
Integrating fault detection and isolation with model predictive control
Authors: Lennox Barry
Published: December 2004

This paper illustrates how the application of partial least squares (PLS) can be extended to provide an integrated solution to fault detection and isolation, inferential estimation and model predictive control. It is shown that if PLS is used to identify a dynamic model of a plant then the latent variables of the model can identify the suitability of using this model under current conditions. This functionality enables automated model switching in piecewise linear systems. A further advantage of the proposed technique is that the inner structure of the model can be used to provide fault detection and isolation capabilities. By extending the approach to control systems and integrating a dynamic model, identified using the PLS algorithm, within a model predictive controller, similar benefits, such as automatic model selection can be achieved for the control system. The proposed approach is illustrated through its application to the Tennessee Eastman challenge process. Copyright © 2004 John Wiley & Sons, Ltd.
Isolating the root cause of propagated oscillations in process plants
Authors: Zang Xiaoyun , Howell John
Published: December 2004

Oscillations are a common type of propagated disturbance, whose sources might be attributable to a number of different phenomena such as poor controller tuning or actuator nonlinearity. A number of data‐driven methods have already been proposed to isolate the source loop of nonlinearity induced plant‐wide oscillations. Amongst these the bi‐amplitude ratio index, correlation dimension, maximal Lyapunov exponent, nonlinearity index and spectral ICA show promise. The propagation of oscillations is first examined in order to gain an understanding of how this might affect the performances of the various techniques. The various methods are then described and their performance on a set of simulation generated data and two industrial case studies are compared. Copyright © 2004 John Wiley & Sons, Ltd.
Fault detection and estimation for nonlinear systems with linear output structure
Authors: Wang Hong , Shen Ling
Published: December 2004

In this paper, a new formulation of fault detection and estimation algorithm has been presented for a class of known nonlinear dynamic systems with a linear output structure. Under certain assumptions on the nonlinear dynamics of the system and its model uncertainty, an adaptive observer‐based approach is established so as to construct several effective residual signals that can be used to perform the required fault detection and estimation. A parameter dependent Lyapunov function is used to formulate a set of adaptive tuning rules for the time‐varying parameters involved in both the adaptive observer and the fault estimation error. It has been shown that the algorithms can be applied to estimate both constants and slow‐drifting faults with convergent residual signals. A simple simulation example is included to illustrate the use of the proposed methods and encouraging results have been obtained. Copyright © 2004 John Wiley & Sons, Ltd.
Microstructure and Strengthening Mechanism of Oxide Lanthanum Dispersion Strengthened Molybdenum Alloy
Authors: Zhang G.‐J. , Sun Y.‐J. , Niu R.‐M. , Sun J. , Wei J.‐F. , Zhao B.‐H. , Yang L.‐X.
Published: December 2004

The strength of molybdenum alloys dispersed by different mass fraction oxide lanthanum particles has been determined at room temperature and related to the microstructure. It was found that fine oxide lanthanum particles incur a fine grain size and contribute much to the alloys strength. The quantitative relationships between the strengths of the alloys and the sizes, volume fraction of oxide lanthanum particles and the grain sizes were presented.
An Mg‐Al‐Zn Alloy with Verry High Specific Strength and Superior High‐strain‐rate Superplasticity Processed by Reciprocating Extrusion
Authors: Lee S.‐W. , Wang H.‐Y. , Chen Y.‐L. , Yeh J.‐W. , Yang C.‐F.
Published: December 2004

A novel method called “Reciprocating Extrusion” is exploited to realize the high potential of Mg‐15Al‐1Zn alloy to exhibit superior mechanical properties and superplasticity, bypassing the costly and complicated RS+PM route. Such refined alloys exhibit unique high‐strain‐rate superplasticity at 325 °C and maximum elongation larger than 1610% at 1×10–2 s–1. They also possess greater strength/density than 7075‐T736 Al alloys.
Large‐scale purification of oligonucleotides by extraction and precipitation with butanole
Authors: Wolfrum Christian , Josten Andre , Bauer Georg , Götz Peter
Published: December 2004

Today the synthesis of oligonucleotides is a well‐established process. Using automatic synthesizers even kilogram quantities can be produced in a few hours. However, the purification of the final product is still time‐consuming and needs a complex apparatus. In this article, a simple and fast purification method for the large‐scale syntheses of oligonucleotides is described. According to the method of Sawadago and van Dyke ([1991] Nucleic Acids Res 19:674–675) for small‐scale oligonucleotide purification, oligonucleotides in μmol to mmol amounts were purified by liquid–liquid extraction using butanole as the extraction liquid. Choosing appropriate ratios of extraction liquid to oligonucleotide solution, simultaneous purification and precipitation could be achieved. It was found that the yield of the purified oligonucleotide was mainly affected by the temperature. Yield decreased with increasing temperature. The use of this improved extraction procedure allows the purification of gram to kilogram quantities of oligonucleotides in less than a day with simple equipment and high yield. © 2004 Wiley Periodicals, Inc.
Antibacterial and antifungal efficacy of surface functionalized polymeric beads in repeated applications
Authors: Hu F. X. , Neoh K. G. , Cen L. , Kang E. T.
Published: December 2004

A simple method was developed to prepare polymeric microbeads with antibacterial and antifungal properties. The microbeads of approximately spherical shape and narrow size distribution were prepared from a mixture of poly (4‐vinyl pyridine) (P4VP) and poly (vinylidene fluoride) (PVDF) by a phase inversion technique and subsequently derivatized with alkyl bromides having 4–10 carbon atoms. The quaternization of the pyridine groups into pyridinium groups confers the surface with highly effective and long‐lasting antibacterial and antifungal properties, as shown by the effect on Escherichia coli and Aspergillus niger. Upon contact with the N‐alkylated beads, the bacteria and fungal spores are lysed and intracellular constituents leach out into the medium. The efficacy of the alkyl chains in disrupting the cell membrane was investigated. The stability of the functional group and microbiocidal effectiveness of the microbeads in repeated applications was also assessed. © 2004 Wiley Periodicals, Inc.
Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis
Authors: Lang H , Sotiropoulos G C , Dömland M , Frühauf N R , Paul A , Hüsing J , Malagó M , Broelsch C E
Published: December 2004

Background

Hepatocellular carcinoma (HCC) arising in normal liver parenchyma is rare and the outcome after hepatectomy is not well documented.

Methods

Between June 1998 and September 2003, 33 patients without viral hepatitis underwent resection for HCC in a non-cirrhotic, non-fibrotic liver. Data were analysed with regard to operative details, pathological findings including completeness of resection, and outcome as measured by tumour recurrence and survival.

Results

Twenty-three major hepatectomies and ten segmentectomies or bisegmentectomies were performed. After potentially curative resection, 19 of 29 patients were alive at a median follow-up of 25 months, with calculated 1- and 3-year survival rates of 87 and 50 per cent respectively. Survival was significantly better after resection of tumours without vascular invasion (3-year survival rate 89 versus 18 per cent; P = 0·024). Disseminated recurrence developed in nine of 29 patients, leading to death within 28 months of operation in all but one of the nine.

Conclusion

These data justify hepatic resection for HCC arising in non-cirrhotic, non-fibrotic liver without underlying viral hepatitis. Liver transplantation is rarely indicated because the outcome is good after resection of tumours without vascular infiltration, whereas vascular invasion is invariably associated with diffuse extrahepatic recurrence.