bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reform of Legal Education in East Asia
Authors: Miyazawa Setsuo , Chan Kay-Wah , Lee Ilhyung
Published: August 2008

Legal education in East Asia, particularly in China, Japan, and Korea, is undergoing fundamental changes, both institutionally and pedagogically. A common feature of those changes is the introduction of elements of the American system of legal education. Although traditional legal education in these countries has been provided at an undergraduate level and has not been considered professional legal education, recent and current reforms in those countries are either adding postgraduate professional law schools to existing undergraduate legal education or replacing undergraduate legal education with postgraduate professional law schools. The main parts of this review describe key features of those reforms in the three countries. The conclusion draws some theoretical implications from similarities and differences among the three countries, particularly in terms of the role of the top elite as agents of reform and of the constraints of different local conditions.
TreeGenes: A Forest Tree Genome Database
Authors: Wegrzyn Jill L. , Lee Jennifer M. , Tearse Brandon R. , Neale David B.
Published: August 2008

The Dendrome Project and associated TreeGenes database serve the forest genetics research community through a curated and integrated web-based relational database. The research community is composed of approximately 2 000 members representing over 730 organizations worldwide. The database itself is composed of a wide range of genetic data from many forest trees with focused efforts on commercially important members of the Pinaceae family. The primary data types curated include species, publications, tree and DNA extraction information, genetic maps, molecular markers, ESTs, genotypic, and phenotypic data. There are currently ten main search modules or user access points within this PostgreSQL database. These access points allow users to navigate logically through the related data types. The goals of the Dendrome Project are to (1) provide a comprehensive resource for forest tree genomics data to facilitate gene discovery in related species, (2) develop interfaces that encourage the submission and integration of all genomic data, and to (3) centralize and distribute existing and novel online tools for the research community that both support and ease analysis. Recent developments have focused on increasing data content, functional annotations, data retrieval, and visualization tools. TreeGenes was developed to provide a centralized web resource with analysis and visualization tools to support data storage and exchange.
Comparison of Two Mechanics-Based Methods for Simplified Structural Analysis in Vulnerability Assessment
Authors: Crowley H. , Borzi B. , Pinho R. , Colombi M. , Onida M.
Published: August 2008

Analytical vulnerability assessment methods should ideally be validated or verified by comparing their damage predictions with actual observed damage data. However, there are a number of difficulties related to the comparison of analytical damage predictions with observed damage; for example, there are large uncertainties related to the prediction of the ground motions to which the damaged buildings have been subjected. Until such problems can be resolved, it is worthwhile considering the mechanics of simplified analytical vulnerability assessment methods and validating this part of the methodology through comparisons with detailed structural models. This paper looks at two mechanics-based vulnerability assessment methods (DBELA and SP-BELA) and compares the nonlinear static response predicted with these methods with finite elements-based nonlinear analyses of prototype buildings. A comparison of the predicted response of urban populations of buildings using the two methods is then carried out, and the influence of these differences on vulnerability curves is studied.
Laparoscopic Extravesical Ureteral Reimplantation: Technique
Authors: Capolicchio John-Paul
Published: August 2008

Laparoscopic extravesical ureteral reimplantation in children is currently a technically demanding procedure with sparse literature to aid in mastering the learning curve. We present our most recent technique and lessons learned after 20 cases in children 4–15 years of age. The literature is also reviewed to encapsulate the current state-of-the-art.
Fission Product Transport and Source Terms in HTRs: Experience from AVR Pebble Bed Reactor
Authors: Moormann Rainer
Published: August 2008

Fission products deposited in the coolant circuit outside of the active core play a dominant role in source term estimations for advanced small pebble bed HTRs, particularly in design basis accidents (DBA). The deposited fission products may be released in depressurization accidents because present pebble bed HTR concepts abstain from a gas tight containment. Contamination of the circuit also hinders maintenance work. Experiments, performed from 1972 to 88 on the AVR, an experimental pebble bed HTR, allow for a deeper insight into fission product transport behavior. The activity deposition per coolant pass was lower than expected and was influenced by fission product chemistry and by presence of carbonaceous dust. The latter lead also to inconsistencies between Cs plate out experiments in laboratory and in AVR. The deposition behavior of Ag was in line with present models. Dust as activity carrier is of safety relevance because of its mobility and of its sorption capability for fission products. All metal surfaces in pebble bed reactors were covered by a carbonaceous dust layer. Dust in AVR was produced by abrasion in amounts of about 5 kg/y. Additional dust sources in AVR were ours oil ingress and peeling of fuel element surfaces due to an air ingress. Dust has a size of about 1  m, consists mainly of graphite, is partly remobilized by flow perturbations, and deposits with time constants of 1 to 2 hours. In future reactors, an efficient filtering via a gas tight containment is required because accidents with fast depressurizations induce dust mobilization. Enhanced core temperatures in normal operation as in AVR and broken fuel pebbles have to be considered, as inflammable dust concentrations in the gas phase.
Fasting Compared With Nonfasting Lipids and Apolipoproteins for Predicting Incident Cardiovascular Events
Authors: Mora Samia , Rifai Nader , Buring Julie E. , Ridker Paul M
Published: August 2008

Background—

Although guidelines recommend measuring fasting lipids for initial screening of adults without cardiovascular disease (CVD), recent studies suggest that nonfasting triglycerides may be superior to fasting. Whether fasting status alters associations of nontriglyceride lipids with CVD is unclear.

Methods and Results—

In a prospective study of 26 330 healthy women (19 983 fasting; 6347 nonfasting), associations of baseline lipids with incident CVD (754 fasting; 207 nonfasting) were examined over an 11-year follow-up. Except for triglycerides, lipid concentrations differed minimally (<5%) for fasting versus nonfasting. However, stronger associations with CVD were noted for fasting total cholesterol (adjusted fasting hazard ratio [HR], 1.22 per 1-SD increment; 95% CI, 1.14 to 1.30; nonfasting HR, 1.07; 95% CI, 0.93 to 1.21), low-density lipoprotein (LDL) cholesterol (fasting HR, 1.21; 95% CI, 1.13 to 1.29; nonfasting HR, 1.00; 95% CI, 0.87 to 1.15), apolipoprotein B-100 (fasting HR, 1.36; 95% CI, 1.27 to 1.45; nonfasting HR, 1.20; 95% CI, 1.05 to 1.36), non–high-density lipoprotein (HDL) cholesterol (fasting HR, 1.29; 95% CI, 1.21 to 1.38; nonfasting HR, 1.15; 95% CI, 1.01 to 1.31), and apolipoprotein B-100/A-1 ratio (fasting HR, 1.39; 95% CI, 1.30 to 1.48; nonfasting HR, 1.18; 95% CI, 1.09 to 1.27). Compared with fasting levels, nonfasting HDL cholesterol, apolipoprotein A-1, and total/HDL cholesterol ratio had similar associations, and triglycerides had a stronger association, with CVD. Significant interactions were seen for LDL cholesterol and apolipoprotein B-100/A-1 ratio with fasting status (
P
for interaction=0.03 and <0.001, respectively).

Conclusions—

This study demonstrates that HDL cholesterol, triglycerides, total/HDL cholesterol ratio, and apolipoprotein A-1 predict CVD when measured nonfasting. By contrast, total, LDL, and non-HDL cholesterol, in addition to apolipoprotein B-100 and B-100/A-1 ratio, provide less useful CVD risk information when nonfasting, despite small changes in their concentrations. Guidelines for lipid screening may need to consider these differences.
Role of the Multidomain Protein Spinophilin in Blood Pressure and Cardiac Function Regulation
Authors: da Costa-Goncalves Andrey C. , Tank Jens , Plehm Ralph , Diedrich Andre , Todiras Mihail , Gollasch Maik , Heuser Arnd , Wellner Maren , Bader Michael , Jordan Jens , Luft Friedrich C. , Gross Volkmar
Published: August 2008

Spinophilin controls intensity/duration of G protein-coupled receptor signaling and thereby influences synaptic activity. We hypothesize that spinophilin affects blood pressure through central mechanisms. We measured blood pressure and heart rate in SPL-deficient (SPL−/−), heterozygous SPL-deficient (SPL+/−), and wild-type (SPL+/+) mice by telemetry combined with fast Fourier transformation. We also assessed peripheral vascular reactivity and performed echocardiography. SPL−/−had higher mean arterial pressure than SPL+/−and SPL+/+(121±2, 112±1, and 113±1 mm Hg). Heart rate was inversely related to spinophilin expression (SPL−/−565±0.4, SPL+/−541±5, SPL+/+525±8 bpm). The blood pressure response to prazosin, trimethapane, and the heart rate response to metoprolol were stronger in SPL−/−than SPL+/+mice, whereas heart rate response to atropine was attenuated in SPL−/−. Mesenteric artery vasoreactivity after angiotensin II, phenylephrine, and the thromboxane mimetic (U46619) as well as change in heart rate, stroke volume, and cardiac output after dobutamine were similar in SPL−/−and SPL+/+. Baroreflex sensitivity was attenuated in SPL−/−compared with SPL+/−and SPL+/+, which was confirmed by pharmacological testing. Heart rate variability parameters were attenuated in SPL−/−mice. We suggest that an increase in central sympathetic outflow participates in blood pressure and heart rate increases in SPL−/−mice. The elevated blood pressure in SPL−/−mice was associated with attenuated baroreflex sensitivity and decreased parasympathetic activity. Our study is the first to show a role for the spinophilin gene in blood pressure regulation.
Characterization and Functional Analyses of the Human G Protein–Coupled Receptor Kinase 4 Gene Promoter
Authors: Hasenkamp Sandra , Telgmann Ralph , Staessen Jan A. , Hagedorn Claudia , Dördelmann Corinna , Bek Martin , Brand-Herrmann Stefan-Martin , Brand Eva
Published: August 2008

The G protein–coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5′-untranslated region were sufficient for transcriptional activities and composed a powerful
cis
-active element in the distal 293 bp. The −1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein–coupled receptor kinase 4 core promoter resides in the first 1851 bp upstream of its transcription start site. The 4 identified genetic variants within this region exert allele-specific impact on both cell type– and stimulation-dependent transcription and may affect the expression balance of renal G protein–coupled receptor kinase 4.
Turbulence Anisotropy Carried by Streaks in the Neutral Atmospheric Surface Layer
Authors: Dubos Thomas , Drobinski Philippe , Carlotti Pierre
Published: August 2008

The authors investigate the relationships between coherent structures and turbulence anisotropy in the neutral planetary boundary layer by means of empirical orthogonal function (EOF) analysis of large-eddy simulation (LES) data. The simulated flow contains near-surface transient streaks. The EOF analysis extracts the most energetic patterns from the velocity fluctuations based on their second-order spatial correlations. The scale and direction of streaks obtained from a level-by-level analysis of the LES flow field do correspond to that of the EOFs.

It is found that two characteristics of the turbulence anisotropy depend on whether or not the velocity fluctuations with a given horizontal wave vector present distinct patterns: (i) the vertical extent up to which the turbulent kinetic energy (TKE) is concentrated and (ii) the ratio of the vertical TKE EV to the horizontal TKE EH. Although still present in the complete signal, this anisotropy is strongly emphasized when the signal is projected onto the EOF structures. Hence the coherent structures do indeed carry more anisotropy than the remaining turbulent fluctuations. Furthermore, at horizontal wave vectors where energetic patterns are dominant, the ratio EV/EH takes values close to 0.2, representative of the ratio EV/EH based on the total LES flow and on in situ measurements.
MJO and Tropical Cyclogenesis in the Gulf of Mexico and Eastern Pacific: Case Study and Idealized Numerical Modeling
Authors: Aiyyer Anantha , Molinari John
Published: August 2008

The role of the Madden–Julian oscillation (MJO) in modulating the frequency and location of tropical cyclogenesis over the eastern Pacific and the Gulf of Mexico during August–September 1998 is examined. During the nonconvective phase of the MJO, convection and low-level cyclonic vorticity occurred primarily in conjunction with the intertropical convergence zone (ITCZ). During the convective phase, convection, low-level cyclonic vorticity, and convergence expanded into the northeastern Pacific and the Gulf of Mexico. This was accompanied by enhanced eddy kinetic energy and barotropic energy conversions as compared to the nonconvective phase, consistent with previous research. During the nonconvective phase of the MJO, vertical shear was relatively weaker but tropical cyclones tended to form mainly within the ITCZ. On the contrary, during the convective phase, vertical wind shear exceeded 10 m s−1 over much of this region and tropical cyclone development occurred north of the ITCZ, near the Mexican Pacific coast and the Gulf of Mexico.

Idealized numerical experiments are conducted using a barotropic model with time-invariant basic states representative of the nonconvective and convective phases of the MJO. The simulations indicate that the propagation paths as well as the amplification of the eddies differ substantially between the two phases. During the nonconvective phase, the waves tend to propagate westward into the eastern Pacific. During the convective phase, stronger southerlies steer the waves into the Gulf of Mexico. The MJO-related modulation of tropical cyclogenesis in the eastern Pacific and Gulf of Mexico thus appears to involve anomalous convergence, cyclonic vorticity, vertical wind shear, and differing tracks of easterly waves.
Can a Descending Rain Curtain in a Supercell Instigate Tornadogenesis Barotropically?
Authors: Davies-Jones Robert
Published: August 2008

This paper investigates whether the descending rain curtain associated with the hook echo of a supercell can instigate a tornado through a purely barotropic mechanism. A simple numerical model of a mesocyclone is constructed in order to rule out other tornadogenesis mechanisms in the simulations. The flow is axisymmetric and Boussinesq with constant eddy viscosity in a neutrally stratified environment. The domain is closed to avoid artificial decoupling of a vortex from the storm-scale circulation. In the principal simulation, the initial condition is a balanced, slowly decaying, Beltrami flow describing an updraft that is rotating cyclonically at midlevels around a low pressure center surrounded by a concentric downdraft that revolves cyclonically but has anticyclonic vorticity. The boundary conditions are no slip on the tangential wind and free slip on the radial or vertical wind to accommodate this initial condition and to allow strong interaction of a vortex with the ground.

Precipitation is released through the top above the updraft and falls to the ground near the updraft–downdraft interface in an annular curtain. The downdraft enhancement induced by the precipitation drag upsets the balance of the Beltrami flow. The downdraft and its outflow toward the axis increase low-level convergence beneath the updraft and transport air with moderately high angular momentum downward and inward where it is entrained and stretched by the updraft. The resulting tornado has a corner region with an intense axial jet and low pressure capped by a vortex breakdown and a transition to a broader vortex aloft (a tornado cyclone). A clear slot of subsiding air with anticyclonic vorticity surrounds the vortex. The vertical kinetic energy of the entire circulation declines dramatically prior to tornado formation.
Controls on the Activation and Strength of a High-Latitude Convective Cloud Feedback
Authors: Abbot Dorian S. , Tziperman Eli
Published: August 2008

Previous work has shown that a convective cloud feedback can greatly increase high-latitude surface temperature upon the removal of sea ice and can keep sea ice from forming throughout polar night. This feedback activates at increased greenhouse gas concentrations. It may help to explain the warm “equable climates” of the late Cretaceous and early Paleogene eras (∼100 to ∼35 million years ago) and may be relevant for future climate under global warming. Here, the factors that determine the critical threshold CO2 concentration at which this feedback is active and the magnitude of the warming caused by the feedback are analyzed using both a highly idealized model and NCAR’s single-column atmospheric model (SCAM) run under Arctic-like conditions. The critical CO2 is particularly important because it helps to establish the relevance of the feedback for past and future climates.

Both models agree that increased heat flux into the high latitudes at low altitudes generally decreases the critical CO2. Increases in oceanic heat transport and in solar radiation absorbed during the summer should cause a sharp decrease in the critical CO2, but the effect of increases in atmospheric heat transport depends on its vertical distribution. It is furthermore found (i) that if the onset of convection produces more clouds and moisture, the critical CO2 should decrease, and the maximum temperature increase caused by the convective cloud feedback should increase and (ii) that reducing the depth of convection reduces the critical CO2 but has little effect on the maximum temperature increase caused by the convective cloud feedback. These results should help with interpretation of the strength and onset of the convective cloud feedback as found, for example, in Intergovernmental Panel on Climate Change (IPCC) coupled ocean–atmosphere models with different cloud and convection schemes.
Polarimetric Spectral Filter for Adaptive Clutter and Noise Suppression
Authors: Moisseev Dmitri N. , Chandrasekar V.
Published: August 2008

In this paper, spectral decompositions of differential reflectivity, differential phase, and copolar correlation coefficient are used to discriminate between weather and nonweather signals in the spectral domain. This approach gives a greater flexibility for discrimination between different types of scattering sources present in a radar observation volume. A spectral filter, which removes nonweather signals, is defined based on this method. The performance of this filter is demonstrated on the Colorado State University–University of Chicago–Illinois State Water Survey (CSU–CHILL) observations. It is shown that the resulting filter parameters are adaptively defined for each range sample and do not require an assumption on spectral properties of ground clutter.
Rasta Evolution
Authors: Bedasse Monique
Published: August 2008

This article is concerned with the evolution of the Rastafarian movement through the specific example of the Twelve Tribes of Israel. It provides a serious treatment of Rasta theology by delving into the details surrounding the ways in which Haile Selassie’s divinity is conceptualized. Placing the Rastafarian movement within the context of African resistance in the New World, it argues that as the movement evolves, it remains wedded to the ideals of Ethiopianism.
A Reaction to and Mental Metaevaluation of the Experiential Learning Evaluation Project
Authors: Perry Katye M.
Published: August 2008

Many professors of program evaluation courses look for ways to merge their students' theoretical understanding of program evaluation with practical experience. In this scenario, a professor arranges for his students to evaluate a series of workshops in campus residence halls sponsored by a university diversity center (DC). What follows in this article is a reaction to and mental metaevaluation of both the professor's and students' actions as they engage in this evaluation experience. Their actions are assessed within the context of the Joint Committee on Standards for Educational Evaluation (JCSEE) and the American Evaluation Association (AEA) guiding principles. It concludes with implications this experience has for teachers of program evaluation.
The Emerging Role of Faith Community Nurses in Prevention and Management of Chronic Disease
Authors: McGinnis Sandra L. , Zoske Frances M.
Published: August 2008

Faith community nursing, formerly known as parish nursing, is one model of care that relies heavily on older registered nurses (RNs) to provide population-based and other nonclinical services in community settings. Faith community nursing provides services not commonly available in the traditional health care system (e.g., community case management, community advocacy, community health education). With appropriate support, this model of nursing could be expanded into other settings within the community and has the potential to draw on the skills of experienced RNs to provide communities with services that address unmet health care needs.
Sustainable Tourism
Authors: Stoddard James E. , Evans Michael R. , Davé Dinesh S.
Published: August 2008

Tourist preferences for sustainable tourism products vary according to their demographic and socioeconomic characteristics. Results from a large sample in the Blue Ridge National Heritage Area found preference differences based on gender, age, education level, and income, as well as whether the tourist was a day-tripper or overnight visitor. The study found that the bulk of visitors originate in the southeastern United States, suggesting that promotions for the Blue Ridge area should be directed to those living in North Carolina and vicinity. Results from research such as this can assist sustainable tourism organizations to target promotions of various tourism activities to those who would be most interested.
Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response
Authors: Shi Chung-Sheng , Shi Guey-Yueh , Hsiao Hsi-Min , Kao Yuan-Chung , Kuo Kuan-Lin , Ma Chih-Yuan , Kuo Cheng-Hsiang , Chang Bi-Ing , Chang Chuan-Fa , Lin Chun-Hung , Wong Chi-Huey , Wu Hua-Lin
Published: August 2008

Thrombomodulin (TM), a widely expressing glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. TM appears to exhibit anti-inflammatory ability through both protein C–dependent and –independent pathways. We presently have demonstrated that recombinant N-terminal lectinlike domain of TM (rTMD1) functions as a protective agent against sepsis caused by Gram-negative bacterial infections. rTMD1 caused agglutination of Escherichia coli and Klebsiella pneumoniae and enhanced the macrophage phagocytosis of these Gram-negative bacteria. Moreover, rTMD1 bound to the Klebsiella pneumoniae and lipopolysaccharide (LPS) by specifically interacting with Lewis Y antigen. rTMD1 inhibited LPS-induced inflammatory mediator production via interference with CD14 and LPS binding. Furthermore, rTMD1 modulated LPS-induced mitogen-activated protein kinase and nuclear factor-κB signaling pathway activations and inducible nitric oxide synthase expression in macrophages. Administration of rTMD1 protected the host by suppressing inflammatory responses induced by LPS and Gram-negative bacteria, and enhanced LPS and bacterial clearance in sepsis. Thus, rTMD1 can be used to defend against bacterial infection and inhibit LPS-induced inflammatory responses, suggesting that rTMD1 may be valuable in the treatment of severe inflammation in sepsis, especially in Gram-negative bacterial infections.
Angiogenesis alteration by defibrotide: implications for its mechanism of action in severe hepatic veno-occlusive disease
Authors: Benimetskaya Luba , Wu Sijian , Voskresenskiy Anatoliy M. , Echart Cinara , Zhou Jin-Feng , Shin Joongho , Iacobelli Massimo , Richardson Paul , Ayyanar Kanyalakshmi , Stein C. A.
Published: August 2008

Defibrotide (DF) is a mixture of porcine-derived single-stranded phosphodiester oligonucleotides (9-80-mer; average, 50-mer) that has been successfully used to treat severe hepatic veno-occlusive disease (sVOD) with multiorgan failure (MOF) in patients who have received cytotoxic chemotherapy in preparation for bone marrow transplantation. However, its mechanism of action is unknown. Herein, we show that DF and phosphodiester oligonucleotides can bind to heparin-binding proteins (eg, basic fibroblast growth factor [bFGF] but not vascular endothelial growth factor [VEGF] 165) with low nanomolar affinity. This binding occurred in a length- and concentration-dependent manner. DF can mobilize proangiogenic factors such as bFGF from their depot or storage sites on bovine corneal endothelial matrix. However, these molecules do not interfere with high-affinity binding of bFGF to FGFR1 IIIc but can replace heparin as a required cofactor for binding and hence cellular mitogenesis. DF also protects bFGF against digestion by trypsin and chymotrypsin and from air oxidation. In addition, DF binds to collagen I with low nanomolar affinity and can promote human microvascular endothelial cell-1 (HMEC-1) cell mitogenesis and tubular morphogenesis in three-dimensional collagen I gels. Thus, our data suggest that DF may provide a stimulus to the sinusoidal endothelium of a liver that has suffered a severe angiotoxic event, thus helping to ameliorate the clinical sVOD/MOF syndrome.
Novel insights into the unfolded protein response using Pichia pastoris specific DNA microarrays
Authors: Graf Alexandra , Gasser Brigitte , Dragosits Martin , Sauer Michael , Leparc Germán G , Tüchler Thomas , Kreil David P , Mattanovich Diethard
Published: August 2008

Background

DNA Microarrays are regarded as a valuable tool for basic and applied research in microbiology. However, for many industrially important microorganisms the lack of commercially available microarrays still hampers physiological research. Exemplarily, our understanding of protein folding and secretion in the yeast Pichia pastoris is presently widely dependent on conclusions drawn from analogies to Saccharomyces cerevisiae. To close this gap for a yeast species employed for its high capacity to produce heterologous proteins, we developed full genome DNA microarrays for P. pastoris and analyzed the unfolded protein response (UPR) in this yeast species, as compared to S. cerevisiae.

Results

By combining the partially annotated gene list of P. pastoris with de novo gene finding a list of putative open reading frames was generated for which an oligonucleotide probe set was designed using the probe design tool TherMODO (a thermodynamic model-based oligoset design optimizer). To evaluate the performance of the novel array design, microarrays carrying the oligo set were hybridized with samples from treatments with dithiothreitol (DTT) or a strain overexpressing the UPR transcription factor HAC1, both compared with a wild type strain in normal medium as untreated control. DTT treatment was compared with literature data for S. cerevisiae, and revealed similarities, but also important differences between the two yeast species. Overexpression of HAC1, the most direct control for UPR genes, resulted in significant new understanding of this important regulatory pathway in P. pastoris, and generally in yeasts.

Conclusion

The differences observed between P. pastoris and S. cerevisiae underline the importance of DNA microarrays for industrial production strains. P. pastoris reacts to DTT treatment mainly by the regulation of genes related to chemical stimulus, electron transport and respiration, while the overexpression of HAC1 induced many genes involved in translation, ribosome biogenesis, and organelle biosynthesis, indicating that the regulatory events triggered by DTT treatment only partially overlap with the reactions to overexpression of HAC1. The high reproducibility of the results achieved with two different oligo sets is a good indication for their robustness, and underlines the importance of less stringent selection of regulated features, in order to avoid a large number of false negative results.
Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms
Authors: Honsa Erin , Fricke Thomas , Stephens Alex J , Ko Danny , Kong Fanrong , Gilbert Gwendolyn L , Huygens Flavia , Giffard Philip M
Published: August 2008

Background

Streptococcus agalactiae (Group B Streptococcus (GBS)) is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP) based method for assigning GBS isolates to multilocus sequence typing (MLST)-defined clonal complexes.

Results

It was found that a SNP set derived from the MLST database on the basis of maximisation of Simpsons Index of Diversity provided poor resolution and did not define groups concordant with the population structure as defined by eBURST analysis of the MLST database. This was interpreted as being a consequence of low diversity and high frequency horizontal gene transfer. Accordingly, a different approach to SNP identification was developed. This entailed use of the "Not-N" bioinformatic algorithm that identifies SNPs diagnostic for groups of known sequence variants, together with an empirical process of SNP testing. This yielded a four member SNP set that divides GBS into 10 groups that are concordant with the population structure. A fifth SNP was identified that increased the sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR methods for the interrogation of these SNPs were developed, and used to genotype 116 well characterized isolates.

Conclusion

A five SNP method for dividing GBS into biologically valid groups has been developed. These SNPs are ideal for high throughput surveillance activities, and combining with more rapidly evolving loci when additional resolution is required.
Effect of benthic boundary layer transport on the productivity of Mono Lake, California
Authors: Bruce Louise C , Jellison Robert , Imberger Jörg , Melack John M
Published: August 2008

The significance of the transport of nutrient-rich hypolimnetic water via the benthic boundary layer (BBL) to the productivity of Mono Lake was studied using a coupled hydrodynamic and ecological model validated against field data. The coupled model enabled us to differentiate between the role of biotic components and hydrodynamic forcing on the internal recycling of nutrients necessary to sustain primary productivity. A 4-year period (1991–1994) was simulated in which recycled nutrients from zooplankton excretion and bacterially-mediated mineralization exceeded sediment fluxes as the dominant source for primary productivity. Model outputs indicated that BBL transport was responsible for a 53% increase in the flux of hypolimnetic ammonium to the photic zone during stratification with an increase in primary production of 6% and secondary production of 5%. Although the estimated impact of BBL transport on the productivity of Mono Lake was not large, significant nutrient fluxes were simulated during periods when BBL transport was most active.
A novel survival model of cardioplegic arrest and cardiopulmonary bypass in rats: a methodology paper
Authors: de Lange Fellery , Yoshitani Kenji , Podgoreanu Mihai V , Grocott Hilary P , Mackensen G Burkhard
Published: August 2008

Background

Given the growing population of cardiac surgery patients with impaired preoperative cardiac function and rapidly expanding surgical techniques, continued efforts to improve myocardial protection strategies are warranted. Prior research is mostly limited to either large animal models or ex vivo preparations. We developed a new in vivo survival model that combines administration of antegrade cardioplegia with endoaortic crossclamping during cardiopulmonary bypass (CPB) in the rat.

Methods

Sprague-Dawley rats were cannulated for CPB (n = 10). With ultrasound guidance, a 3.5 mm balloon angioplasty catheter was positioned via the right common carotid artery with its tip proximal to the aortic valve. To initiate cardioplegic arrest, the balloon was inflated and cardioplegia solution injected. After 30 min of cardioplegic arrest, the balloon was deflated, ventilation resumed, and rats were weaned from CPB and recovered. To rule out any evidence of cerebral ischemia due to right carotid artery ligation, animals were neurologically tested on postoperative day 14, and their brains histologically assessed.

Results

Thirty minutes of cardioplegic arrest was successfully established in all animals. Functional assessment revealed no neurologic deficits, and histology demonstrated no gross neuronal damage.

Conclusion

This novel small animal CPB model with cardioplegic arrest allows for both the study of myocardial ischemia-reperfusion injury as well as new cardioprotective strategies. Major advantages of this model include its overall feasibility and cost effectiveness. In future experiments long-term echocardiographic outcomes as well as enzymatic, genetic, and histologic characterization of myocardial injury can be assessed. In the field of myocardial protection, rodent models will be an important avenue of research.
Trichinella spiralis: nurse cell formation with emphasis on analogy to muscle cell repair
Authors: Wu Zhiliang , Sofronic-Milosavljevic Lj , Nagano Isao , Takahashi Yuzo
Published: August 2008

Trichinella infection results in formation of a capsule in infected muscles. The capsule is a residence of the parasite which is composed of the nurse cell and fibrous wall. The process of nurse cell formation is complex and includes infected muscle cell response (de-differentiation, cell cycle re-entry and arrest) and satellite cell responses (activation, proliferation and differentiation). Some events that occur during the nurse cell formation are analogous to those occurring during muscle cell regeneration/repair. This article reviews capsule formation with emphasis on this analogy.
Lateral dislocation of the knee joint after total knee arthroplasty: a case report
Authors: Ugutmen Ender , Ozkan Korhan , Unay Koray , Mahirogullari Mahir , Eceviz Engin , Taser Omer
Published: August 2008

Background

Total knee arthroplasty (TKA) is a successful therapy for functional improvement and pain relief in advanced symptomatic degeneration of the knee joint. But it can be associated with many complications, one of which is instability.

Case presentation

A 70-year-old woman was referred to our hospital because of right knee dislocation after TKA was performed on her right knee due to severe varus deformity and flexion contracture. This instability was caused by persistent MCL tightness and iatrogenic lateral collateral, arcuate ligament, and popliteus tendon injury.

The torn lateral collateral ligament and arcuate ligament were sutured with no. 2 non-absorbable (Ethibond) sutures with plication of the posterolateral knee capsule. A deep-dish liner was inserted to optimize soft tissue tension.

Conclusion

This is a very severe complication, and surgeons must be cautious about ligament balancing and soft tissue resection during TKA for severe varus and valgus deformities.
Ball and socket ankle joint in connection with bilateral tarsal synostosis in a boy with congenital absence of the portal vain: a novel malformation complex
Authors: Zandieh Shahin , Vakil-Adli Anosheh , Hochreiter Josef , Grill Franz , Klaushofer Klaus , Al Kaissi Ali
Published: August 2008

Background

Contracted valgus flat foot in the adolescent is frequently caused by tarsal synostosis or synchondrosis. These synostoses are prevalently symptomatic during adolescence, when by ossifying they block the subtalar joint in valgus. Careful and detailed examinations might reveal additional abnormalities.

Case presentation

A 16-year-old boy of Austrian origin presented with contracted valgus foot associated with tarsal hypomobility and pain. Talonavicular synostosis with ball and socket ankle joint was detected via lateral radiographs and 3 DCT scan. Preoperative laboratory investigations revealed leucocytopenia, and thrombopenia. Computerised abdominal tomography showed portal vein atresia and portopulmonary hypertension.

Conclusion

Clinical research is the corner stone to elucidate the aetiological understandings in patients with malformation complex. The latter is a critical task for the development of scientific bases for preventive strategies. Careful examination for these abnormalities should lead the clinician to earlier referral of patients for additional examination by a specialised medical team. This often enables more focused care for the individual and better characterisation/documentation of the malformation complex. The association of tarsal synostosis and the previously unreported associated occurrences of congenital absence of the portal vein, portopulmonary hypertension, cardiomegaly and splenomegaly have been encountered. We stress that our present patient illustrates and supports the pathophysiological hypotheses that have previously proposed for the concurrent existence of absent portal vein, hepatic nodular hyperplasia and portopulmonary hypertension. Nevertheless, no previous single report signifies the existence of tarsal synostosis in connection with the above-mentioned abnormalities.
TH-17 cells in rheumatoid arthritis
Authors: Shahrara Shiva , Huang QiQuan , Mandelin Arthur M , Pope Richard M
Published: August 2008

Introduction

The aim of this study was to quantify the number of T-helper (TH)-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-γ.

Methods

Peripheral blood (PB) mononuclear cells from normal and RA donors and mononuclear cells from RA SF were examined either without stimulation or after pretreatment with IL-23 followed by stimulation with phorbol myristate acetate (PMA) plus ionomycin (P/I). The abundance of TH-17 cells in RA SF was determined by flow cytometry. IL-17 levels were quantified in synovial tissue from RA, OA and normal individuals by ELISA and IL-23 was identified in SFs by ELISA. RA SF and control in vitro differentiated macrophages were either untreated or treated with the toll-like receptor (TLR) 2 ligand peptidoglycan, and then IL-23, IL-27 and IFN-γ mRNA levels were quantified by real-time polymerase chain reaction (RT-PCR).

Results

Treatment with P/I alone or combined with IL-23 significantly increased the number of TH-17 cells in normal, RA PB and RA SF. With or without P/I plus IL-23, the percentage of TH-17 cells was higher in RA SF compared with normal and RA PB. IL-17 levels were comparable in OA and normal synovial tissues, and these values were significantly increased in RA synovial tissue. Although IL-17 was readily detected in RA SFs, IL-23 was rarely identified in RA SF. However, IL-23 mRNA was significantly increased in RA SF macrophages compared with control macrophages, with or without TLR2 ligation. IL-27 mRNA was also significantly higher in RA SF compared with control macrophages, but there was no difference in IL-27 levels between RA and control macrophages after TLR2 ligation. IFN-γ mRNA was also detectable in RA SF macrophages but not control macrophages and the increase of IFN-γ mRNA following TLR2 ligation was greater in RA SF macrophages compared with control macrophages.

Conclusion

These observations support a role for TH-17 cells in RA. Our observations do not strongly support a role for IL-23 in the generation of TH-17 cells in the RA joint, however, they suggest strategies that enhance IL-27 or IFN-γ might modulate the presence of TH-17 cells in RA.
Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis
Authors: Zhao Xiaoyan , Okeke Nwora Lance , Sharpe Orr , Batliwalla Franak M , Lee Annette T , Ho Peggy P , Tomooka Beren H , Gregersen Peter K , Robinson William H
Published: August 2008

Introduction

There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised.

Methods

We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue.

Results

C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen.

Conclusion

Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients.
Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro
Authors: Otto Natalie M , Schindler Ralf , Lun Andreas , Boenisch Olaf , Frei Ulrich , Oppert Michael
Published: August 2008

Introduction

Hyperglycemia is associated with negative outcomes in various settings of critical illness; infectious complications, especially, seem to be increased. On the other hand, intensive insulin therapy (IIT) has been shown to improve outcome in clinical trials. Whether normoglycemia itself or the application of insulin is responsible for the observed findings is unknown. We therefore tested the effect of glucose and insulin on various immune functions in vitro.

Methods

Human peripheral blood mononuclear cells (PBMCs) were incubated ex vivo with low doses of lipopolysaccharide (LPS). PBMCs were incubated with various osmotic agents, insulin, or a combination of both. Interleukin (IL)-6 and IL-1 cytokine response was measured by enzyme-linked immunosorbent assay. In addition, we investigated the effects of glucose on phagocytosis and oxidative burst in human granulocytes.

Results

Increasing concentrations of both glucose and mannitol significantly enhanced LPS-induced cytokine production. Insulin alone did not alter cytokine production and had only a minor influence in combination with glucose. Phagocytosis and oxidative burst were significantly reduced with increasing concentrations of glucose and mannitol.

Conclusion

Hyperglycemia may lead to inflammation by enhancing cytokine production via the direct effects of hyperosmotic stress. Impaired phagocytosis and oxidative burst under hyperglycemia may weaken defense mechanisms of the host. Our in vitro findings may help to explain the beneficial effects of IIT not only in diabetic but also in critically ill patients.
Allogeneic Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic Leukemia With 17p Deletion: A Retrospective European Group for Blood and Marrow Transplantation Analysis
Authors: Schetelig Johannes , van Biezen Anja , Brand Ronald , Caballero Dolores , Martino Rodrigo , Itala Maija , García-Marco José A. , Volin Liisa , Schmitz Norbert , Schwerdtfeger Rainer , Ganser Arnold , Onida Francesco , Mohr Brigitte , Stilgenbauer Stephan , Bornhäuser Martin , de Witte Theo , Dreger Peter
Published: August 2008

Purpose

Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p–) have a poor prognosis. Although allogeneic hematopoietic stem-cell transplantation (HCT) has the potential to cure patients with advanced CLL, it is not known whether this holds true for patients with 17p–CLL.

Patients and Methods

Baseline data from patients, for whom information on the presence of 17p–CLL was available, were downloaded from the European Group for Blood and Marrow Transplantation database. Additional information on the course of CLL and follow-up was collected with a questionnaire.

Results

A total of 44 patients with 17p–CLL received allogeneic HCT between March 1995 and July 2006 from a matched sibling (n = 24) or an alternative donor (n = 20). 17p–CLL had been diagnosed by fluorescent in situ hybridization in 82% of patients and by conventional banding in 18% of patients. The median age was 54 years. Before HCT, a median of three lines of chemotherapy had been administered. At HCT, 53% of patients were in remission. Reduced-intensity conditioning was applied in 89% of patients. Acute, grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19 patients were alive, with a median observation time of 39 months (range, 18 to 101 months). Three-year overall survival and progression-free survival rates were 44% and 37%, respectively. The cumulative incidence of progressive disease at 4 years was 34%. No late relapse occurred in nine patients with a follow-up longer than 4 years.

Conclusion

Allogeneic HCT has the potential to induce long-term disease-free survival in patients with 17p–CLL.