bluuebunny/crossref_metadata_2025 huggingface dataset:
Data-parallel techniques for simulating a mega-scale agent-based model of systemic inflammatory response syndrome on graphics processing units
Authors: Alberts Samuel , Keenan Michael K , D’Souza Roshan M , An Gary
Published: November 2011

Agent-based modeling is increasingly being used for computer simulation of complex biological systems. An agent-based model (ABM) is a bottom-up simulation where the bulk dynamics of the model result from the local interactions of its individual constituents or agents. However, due to emergent qualities of ABMs, bulk behaviors may be sensitive to the size of the model as determined by the population of individuals. Therefore, in certain circumstances it may be critical to closely match the simulation size with the actual system. This may be particularly true in biological systems, where multiple large-scale heterogeneous populations can range into millions or even billions of individual cells/agents. Most existing ABM simulation toolkits are designed for serial computing and canno*t effectively simulate such mega-scale systems from a run-time standpoint. In this paper, we investigate data-parallel ABM implementations on graphics processing units to address the scalability issue of ABMs. As an example, we have implemented an abstracted version of the Systemic Inflammatory Response Syndrome ABM. We also implemented a serial version to confirm statistical accuracy. Our results show that parallelization on graphics processing units offers a substantial gain in performance without a loss in accuracy.
“In Forms That Are Familiar and Yet-to-Be Invented”
Authors: Powers Matthew
Published: November 2011

Changes in the technologies of news production do not simply modify journalistic practices; they also introduce what might be considered technologically specific forms of work. These work forms are rooted in the affordances of novel technical capacities while also making claims about the journalistic nature of such work. How do journalists discuss the emergence of these technologically specific forms? When are new work forms seen as contributing to the practices of journalism and when are they seen as threatening it? Drawing on archival research of industry discussions, this article argues that such work is discussed in three distinct ways: (1) as exemplars of continuity; (2) as threats to be subordinated; and (3) as possibilities for journalistic reinvention. Each mode, it is argued, points to different understandings of the relationship between journalistic work and technology and carries different implications about the changing nature of journalistic work in the digital age.
Karl-Otto Apel and the Study of Communication
Authors: Sikka Tina
Published: November 2011

In this article the author reads the German philosopher Karl-Otto Apel as a communication theorist. After a brief biographical introduction, the author examines five fields of significance pertinent to Apel’s thought and to the study of communication: First is Apel’s work on the so-called understanding and explanation controversy, or Erklaeren-verstehen (E-V) in German; second is Apel’s theory of discourse ethics; third, there are a series of essays through which the readers also get a fuller account of Apel’s use of Charles Sanders Peirce’s pragmatic approach to philosophy; and fourth, there are several articles’ that reflect Apel’s contributions to global politics based on his transcendental pragmatic framework. Finally, there is a lengthy discussion of a few other areas of significance that reveals Apel’s conceptual relationship to theories of communication. The first of these areas or fields consists of the way in which Apel takes up hermeneutics. The second is his definition and use of the “self-recuperative principle” while the third consists of his ongoing conversations with social philosophers Jürgen Habermas and Enrique Dussel.
Gender identities and practices: Interpreting women entrepreneurs’ narratives
Authors: García María-Cristina Díaz , Welter Friederike
Published: November 2011

Previous research has shown that the discourse on womanhood is in conflict with that of entrepreneurship. This qualitative study examines how women construct their identities differently, finding that some of them perceive dissonance between womanhood and entrepreneurship discourses whereas others do not. The results indicate specific ways of constructing gender identity which result in gendered practices: how women act as entrepreneurs by ‘doing’ and ‘redoing’ gender. Since identity construction is contextually produced, other variables intersect with gender in establishing women’s status position. Women with higher status, engage in ‘redoing’ gender, trying to add value to it. The results offer new insights for those interested in promoting women entrepreneurs, by illustrating how gendered practices are used as strategic devices in doing business. In this regard, we argue that stories concerning women’s repertoire of business practices allow us to challenge the taken-for-granted assumptions of gender neutrality regarding typical business behaviour and entrepreneurship.
Effect of welding sequence and direction on angular distortions in butt-welded plates
Authors: Seyyedian Choobi Mahsa , Haghpanahi Mohammad , Sedighi Mohammad
Published: November 2011

During arc welding process, non-uniform heating and cooling lead to non-uniform expansion and contraction of the weld and surrounding base metal which result in undesirable residual stresses and distortions in the welded joint. Among different types of welding distortions, angular distortions produced by butt welding of plates are of major concern in industry. Various methods are currently being used to control and reduce angular distortions. Among different types of distortion control methods the ones which can also reduce residual stresses are preferred. In this paper, the effect of welding sequence and direction on reduction of welding-induced angular distortions in single-pass butt-welded 304 stainless plates and also their effect on residual stresses are investigated by numerical simulation. Welding simulation has been performed using a three-dimensional thermo-elastic–plastic finite element model. In order to verify the numerical model, experiments have also been carried out and temperature histories, angular distortions and residual stresses have been measured. The results of this study showed that welding sequence and direction have a great influence on angular distortions. The results revealed that welding symmetrically from center towards the edges of the plate not only decreases angular distortions but also reduces residual stresses. Thus, welding symmetrically from center towards the edges of the plate can be used as a cost-effective method for mitigating angular distortions in butt-welded plates.
Atypical Antipsychotic Drugs in the Treatment of Parkinson’s Disease
Authors: Friedman Joseph H.
Published: November 2011

Parkinson’s disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.
Targeting Treatment-Resistant Depression
Authors: Mathys Monica , Mitchell Brian G.
Published: November 2011

Only 50% of depressed patients achieve remission of symptoms after 2 trials of antidepressants. Therefore one half of patients are considered treatment resistant. Studies have shown that with each failed antidepressant, chances of remission continue to decline. Untreated depressive symptoms lead to impaired social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization. Clinicians recognize there is an urgent need to find an efficacious treatment, but it becomes more difficult to decide on an appropriate therapy once a patient has failed 2 to 3 trials of antidepressants. An evidence-based review was performed to assess the efficacy and safety of several different antidepressant strategies to help the clinician decide which may be beneficial for specific patients.
If They Were to Vote, They Would Vote for Us
Authors: Koudenburg Namkje , Postmes Tom , Gordijn Ernestine H.
Published: November 2011

In two field studies, we examined whether voters overestimate support for their political party among nonvoters. In Study 1, voters estimated the percentage of votes their party would receive in an upcoming election, and this percentage increased when voters estimated the percentage of votes their party would receive if nonvoters also were to vote. In Study 2, participants overestimated support for their party even when we made them explicitly aware of current levels of this support by presenting them with poll-based forecasts of election results. Furthermore, Study 2 demonstrated that commitment to vote for a specific party predicted the degree of overestimation. Our results imply that highly committed voters are particularly likely to project support for their party onto nonvoters. Implications for the literature on social projection and social identity are discussed.
Piezoelectric wind energy harvester for low-power sensors
Authors: Sirohi Jayant , Mahadik Rohan
Published: November 2011

There has been increasing interest in wireless sensor networks for a variety of outdoor applications including structural health monitoring and environmental monitoring. Replacement of batteries that power the nodes in these networks is maintenance intensive. A wind energy–harvesting device is proposed as an alternate power source for these wireless sensor nodes. The device is based on the galloping of a bar with triangular cross section attached to a cantilever beam. Piezoelectric sheets bonded to the beam convert the mechanical energy into electrical energy. A prototype device of size approximately 160 × 250 mm was fabricated and tested over a range of operating conditions in a wind tunnel, and the power dissipated across a load resistance was measured. A maximum power output of 53 mW was measured at a wind velocity of 11.6 mph. An analytical model incorporating the coupled electromechanical behavior of the piezoelectric sheets and quasi-steady aerodynamics was developed. The model showed good correlation with measurements, and it was concluded that a refined aerodynamic model may need to include apparent mass effects for more accurate predictions. The galloping piezoelectric energy-harvesting device has been shown to be a viable option for powering wireless sensor nodes in outdoor applications.
Moving to Opportunity
Authors: Gay Claudine
Published: November 2011

In 1994, the U.S. Department of Housing and Urban Development launched the Moving to Opportunity for Fair Housing Demonstration Program (MTO), a lottery that offered poor families vouchers to move out of public housing into private apartments. Drawing on recently collected vote history data, this study reveals that MTO has had the unintended consequence of reducing voter turnout among participating adults. The low turnout may be due to the loss of social ties that accompanied mobility. The findings suggest that residential mobility, a popular tool in the fight against poverty, may strain poor Americans’ weak ties to the political system.
Sir Harold Gillies CBE, FRCS: The father of modern plastic surgery
Authors: Shastri-Hurst N
Published: November 2011

The Hippocratic dictum states that war is the best school for surgeons. A perfect exemplar of this is the life of Sir Harold Gillies, who pioneered the techniques of plastic surgery and, in particular, the pedicle flap during World War I. His work and tutelage not only encouraged an entire cadre of future surgeons but also played a vital role in the recovery, both mental and physical, of a great number of patients. His legacy of meticulous planning and preparation stands firm today.
Outcomes of Shared Mental Models of Team Members in Cross Training and High-Intensity Simulations
Authors: Espevik Roar , Johnsen Bjørn Helge , Eid Jarle
Published: November 2011

The present study examined whether shared mental models of team members’ characteristics were associated with team outcomes (i.e., performance, communication, and physical arousal) in cross training and a high-intensity simulation requiring coordinated team action. In a quasi-experimental design, 36 Navy officer cadets were randomly assigned to 12 newly formed tactical teams in the no shared mental modal condition (NoSMM). In contrast, 33 Navy officer cadets in 11 seasoned teams were included in the shared mental model condition (TMSMM). All teams were exposed to the same naval scenarios in their cross training and simulation exercise. The results showed that teams with TMSMM had superior performance and communication patterns characterized by updates and confirmations compared to the NoSMM teams during cross training and simulation. During cross training, TMSMM teams provided more backup than NoSMM teams. These findings suggest that shared mental models of team member are transferable through tasks and enhance the effects of cross training. The present study extends previous research indicating that shared mental models of team members represent an independent, adaptive asset at the group level that enhances team efficiency.
Friend or Foe, Champ or Chump? Social Conformity and Superiority Goals Activate Warmth-Versus Competence-Based Social Categorization Schemas
Authors: Cohrs J. Christopher , Asbrock Frank , Sibley Chris G.
Published: November 2011

Evaluations of individuals and social groups refer to two basic dimensions of social judgment: warmth and competence. Although previous research has explored the antecedents and consequences of these evaluations, there is a lack of understanding of the conditions under which warmth and competence information is used for social categorization in the first place. The present research developed a novel measure of individuals’ tendencies to categorize persons in terms of competence versus warmth and tested whether these tendencies are predicted by chronic (Study 1, N = 301) and experimentally induced (Study 2, N = 69) social conformity and superiority goals. Social conformity goals predicted greater relative use of warmth information, while superiority goals predicted greater relative use of competence information in categorizing persons. These findings attest to the relevance of chronic as well as contextually induced goals at an early stage of social information processing related to social categorization.
Effect of annealing on tensile properties of electrodeposited nanocrystalline Ni with broad grain size distribution
Authors: Zheng Y D , Dai P Q , Xu W C , Hu S R
Published: November 2011

The microstructures and tensile properties of electrodeposited nanocrystalline Ni (nc-Ni) with a broad grain size distribution after annealing at 150, 200 and 300°C for 500 s were investigated. The as deposited broad grain size distribution nc-Ni sample exhibited a moderate strength σUTS of ∼1107 MPa but a markedly enhanced ductility ϵTEF of ∼10, compared with electrodeposited nc-Ni with a narrow grain size distribution. Annealing below 200°C increased the strength but caused a considerably reduction in tensile elongation. This behaviour is attributed to the grain boundary relaxation and the increased order of grain boundaries after annealing, which can make the grain boundary activities, such as the grain boundary sliding and grain rotations, more difficult. Further annealing at 300°C decreased both the yield strength and tensile elongation significantly due to significant grain growth.
Bending properties and fracture mechanisms of ZnO and ZnAl2O4 coated aluminium borate whisker reinforced aluminium composites
Authors: Wang L P , Yue H Y , Guo E J , Fei W D , Kang F W , Yu Z M
Published: November 2011

ZnO and ZnAl2O4 coated aluminium borate whisker (ABOw) reinforced pure aluminium composites were fabricated by squeeze casting. The effects of the coatings on the bending properties of the composites were investigated. On the analysis of fractographs, the fracture mechanisms of the composites under bending were also investigated. The results show that both ZnO and ZnAl2O4 coatings of ABOw can significantly increase the bending properties of ABOw reinforced aluminium composite. In ABOw/Al, ABOw/ZnO/Al and ABOw/ZnAl2O4/Al composites, the interface debonding, near interface fracture and near interface fracture and ABOw fracture dominate the fracture of each composite during bending respectively.
Mechanical properties of undercooled aluminium alloys and their implementation in quenching simulation
Authors: Reich M , Kessler O
Published: November 2011

The mechanical properties of aluminium alloys with non-equilibrium microstructures necessary for heat treatment simulation are not available. Therefore, compression tests of undercooled aluminium alloys such as AlSi1MgMn and AlZn4·5Mg1 have been performed in a quenching and deformation dilatometer with varying quenching rates and quenching finish temperatures. The compressive load on quenching finish temperature was applied immediately after quenching. The mechanical properties such as yield strength and strain hardening are strongly dependent on quenching rates and finish temperatures of quenching. Flow curves depending on quenching rates and quenching finish temperatures have been implemented in a quenching simulation by the finite element method. For the cooling process of extrusion profiles in water and in a gas nozzle field, the simulation results are presented.
Identification of VLDLR as a novel endothelial cell receptor for fibrin that modulates fibrin-dependent transendothelial migration of leukocytes
Authors: Yakovlev Sergiy , Mikhailenko Irina , Cao Chunzhang , Zhang Li , Strickland Dudley K. , Medved Leonid
Published: November 2011

While testing the effect of the (β15-66)2 fragment, which mimics a pair of fibrin βN-domains, on the morphology of endothelial cells, we found that this fragment induces redistribution of vascular endothelial–cadherin in a process that is inhibited by the receptor-associated protein (RAP). Based on this finding, we hypothesized that fibrin may interact with members of RAP-dependent low-density lipoprotein (LDL) receptor family. To test this hypothesis, we examined the interaction of (β15-66)2, fibrin, and several fibrin-derived fragments with 2 members of this family by ELISA and surface plasmon resonance. The experiments showed that very LDL (VLDL) receptor (VLDLR) interacts with high affinity with fibrin through its βN-domains, and this interaction is inhibited by RAP and (β15-66)2. Furthermore, RAP inhibited transendothelial migration of neutrophils induced by fibrin-derived NDSK-II fragment containing βN-domains, suggesting the involvement of VLDLR in fibrin-dependent leukocyte transmigration. Our experiments with VLDLR-deficient mice confirmed this suggestion by showing that, in contrast to wild-type mice, fibrin-dependent leukocyte transmigration does not occur in such mice. Altogether, the present study identified VLDLR as a novel endothelial cell receptor for fibrin that promotes fibrin-dependent leukocyte transmigration and thereby inflammation. Establishing the molecular mechanism underlying this interaction may result in the development of novel inhibitors of fibrin-dependent inflammation.
Transcriptome analysis of Bupleurum chinense focusing on genes involved in the biosynthesis of saikosaponins
Authors: Sui Chun , Zhang Jie , Wei Jianhe , Chen Shilin , Li Ying , Xu Jiesen , Jin Yue , Xie Caixiang , Gao Zhihui , Chen Hongjiang , Yang Chengmin , Zhang Zheng , Xu Yanhong
Published: November 2011

Background

Bupleurum chinenseDC. is a widely used traditional Chinese medicinal plant. Saikosaponins are the major bioactive constituents ofB. chinense, but relatively little is known about saikosaponin biosynthesis. The 454 pyrosequencing technology provides a promising opportunity for finding novel genes that participate in plant metabolism. Consequently, this technology may help to identify the candidate genes involved in the saikosaponin biosynthetic pathway.

Results

One-quarter of the 454 pyrosequencing runs produced a total of 195, 088 high-quality reads, with an average read length of 356 bases (NCBI SRA accession SRA039388). Ade novoassembly generated 24, 037 unique sequences (22, 748 contigs and 1, 289 singletons), 12, 649 (52.6%) of which were annotated against three public protein databases using a basic local alignment search tool (E-value ≤1e-10). All unique sequences were compared with NCBI expressed sequence tags (ESTs) (237) and encoding sequences (44) from theBupleurumgenus, and with a Sanger-sequenced EST dataset (3, 111). The 23, 173 (96.4%) unique sequences obtained in the present study represent novelBupleurumgenes. The ESTs of genes related to saikosaponin biosynthesis were found to encode known enzymes that catalyze the formation of the saikosaponin backbone; 246 cytochrome P450 (P450s) and 102 glycosyltransferases (GTs) unique sequences were also found in the 454 dataset. Full length cDNAs of 7P450s and 7 uridine diphosphateGTs (UGTs) were verified by reverse transcriptase polymerase chain reaction or by cloning using 5' and/or 3' rapid amplification of cDNA ends. TwoP450s and threeUGTs were identified as the most likely candidates involved in saikosaponin biosynthesis. This finding was based on the coordinate up-regulation of their expression withβ-ASin methyl jasmonate-treated adventitious roots and on their similar expression patterns withβ-ASin variousB. chinensetissues.

Conclusions

A collection of high-quality ESTs forB. chinenseobtained by 454 pyrosequencing is provided here for the first time. These data should aid further research on the functional genomics ofB. chinenseand otherBupleurumspecies. The candidate genes for enzymes involved in saikosaponin biosynthesis, especially theP450s andUGTs, that were revealed provide a substantial foundation for follow-up research on the metabolism and regulation of the saikosaponins.
Integration of a laterally acquired gene into a cell network important for growth in a strain of Vibrio rotiferianus
Authors: Labbate Maurizio , Boucher Yan , Chowdhury Piklu Roy , Stokes Hatch W
Published: November 2011

Background

Lateral Gene Transfer (LGT) is a major contributor to bacterial evolution and up to 25% of a bacterium's genome may have been acquired by this process over evolutionary periods of time. Successful LGT requires both the physical transfer of DNA and its successful incorporation into the host cell. One system that contributes to this latter step by site-specific recombination is the integron. Integrons are found in many diverse bacterial Genera and is a genetic system ubiquitous in vibrios that captures mobile DNA at a dedicated site. The presence of integron-associated genes, contained within units of mobile DNA called gene cassettes makes up a substantial component of the vibrio genome (1-3%). Little is known about the role of this system since the vast majority of genes in vibrio arrays are highly novel and functions cannot be ascribed. It is generally regarded that strain-specific mobile genes cannot be readily integrated into the cellular machinery since any perturbation of core metabolism is likely to result in a loss of fitness.

Results

In this study, at least one mobile gene contained within the Vibrio rotiferianus strain DAT722, but lacking close relatives elsewhere, is shown to greatly reduce host fitness when deleted and tested in growth assays. The precise role of the mobile gene product is unknown but impacts on the regulation of outermembrane porins. This demonstrates that strain specific laterally acquired mobile DNA can be integrated rapidly into bacterial networks such that it becomes advantageous for survival and adaptation in changing environments.

Conclusions

Mobile genes that are highly strain specific are generally believed to act in isolation. This is because perturbation of existing cell machinery by the acquisition of a new gene by LGT is highly likely to lower fitness. In contrast, we show here that at least one mobile gene, apparently unique to a strain, encodes a product that has integrated into central cellular metabolic processes such that it greatly lowers fitness when lost under those conditions likely to be commonly encountered for the free living cell. This has ramifications for our understanding of the role mobile gene encoded products play in the cell from a systems biology perspective.
Secondhand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of cerebrovascular endothelin ETA receptors
Authors: Cao Lei , Xu Cang-Bao , Zhang Yaping , Cao Yong-Xiao , Edvinsson Lars
Published: November 2011

Background

Cigarette smoking enhances the risk of stroke. However, the underlying molecular mechanisms are largely unknown. The present study established an in vivo rat secondhand cigarette smoking (SHS) model and examined the hypothesis that SHS upregulates endothelin receptors with increased cerebrovascular contraction via the Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway.

Results

Rats were exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was recorded by a sensitive myograph. The mRNA and protein expressions for endothelin receptors in cerebral arteries were studied by real-time PCR and Western blot. Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited stronger contractile responses (P < 0.05) mediated by endothelin type A (ETA) receptors. The expressions of mRNA and protein for ETA receptors in the cerebral arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not affect endothelin type B (ETB) receptor-mediated contractions, mRNA or protein levels. The results suggest that SHS upregulates ETA, but not ETB receptors in vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05). Raf-1 inhibitor, GW5074 suppressed the enhanced ETA receptor-mediated contraction, mRNA and protein levels induced by SHS. In addition, GW5074 inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf-1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway.

Conclusions

SHS upregulates cerebrovascular ETA receptors via the Raf/ERK/MAPK pathway, which provides novel understanding of mechanisms involved in SHS-associated stroke.
Considerations on the use of nucleic acid-based amplification for malaria parasite detection
Authors: Proux Stéphane , Suwanarusk Rossarin , Barends Marion , Zwang Julien , Price Ric N , Leimanis Mara , Kiricharoen Lily , Laochan Natthapon , Russell Bruce , Nosten François , Snounou Georges
Published: November 2011

Background

Nucleic acid amplification provides the most sensitive and accurate method to detect and identify pathogens. This is primarily useful for epidemiological investigations of malaria because the infections, often with two or more Plasmodium species present simultaneously, are frequently associated with microscopically sub-patent parasite levels and cryptic mixed infections. Numerous distinct equally adequate amplification-based protocols have been described, but it is unclear which to select for epidemiological surveys. Few comparative studies are available, and none that addresses the issue of inter-laboratory variability.

Methods

Blood samples were collected from patients attending malaria clinics on the Thai-Myanmar border. Frozen aliquots from 413 samples were tested independently in two laboratories by nested PCR assay. Dried blood spots on filter papers from the same patients were also tested by the nested PCR assay in one laboratory and by a multiplex PCR assay in another. The aim was to determine which protocol best detected parasites below the sensitivity level of microscopic examination.

Results

As expected PCR-based assays detected a substantial number of infected samples, or mixed infections, missed by microscopy (27 and 42 for the most sensitive assay, respectively). The protocol that was most effective at detecting these, in particular mixed infections, was a nested PCR assay with individual secondary reactions for each of the species initiated with a template directly purified from the blood sample. However, a lesser sensitivity in detection was observed when the same protocol was conducted in another laboratory, and this significantly altered the data obtained on the parasite species distribution.

Conclusions

The sensitivity of a given PCR assay varies between laboratories. Although, the variations are relatively minor, they primarily diminish the ability to detect low-level and mixed infections and are sufficient to obviate the main rationale to use PCR assays rather than microscopy or rapid diagnostic tests. The optimal approach to standardise methodologies is to provide PCR template standards. These will help researchers in different settings to ensure that the nucleic acid amplification protocols they wish to use provide the requisite level of sensitivity, and will permit comparison between sites.
Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients
Authors: Smid Bouwien E , Rombach Saskia M , Aerts Johannes MFG , Kuiper Symen , Mirzaian Mina , Overkleeft Hermen S , Poorthuis Ben JHM , Hollak Carla EM , Groener Johanna EM , Linthorst Gabor E
Published: November 2011

Background

Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients.

Methods

The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed.

Results

All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5 - 29.2) after 1 year of shortage (p = 0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases.

Conclusions

No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activity.
Recent progress in the study of brown adipose tissue
Authors: Yao Xuan , Shan Shifang , Zhang Ying , Ying Hao
Published: November 2011

Brown adipose tissue in mammals plays a critical role in maintaining energy balance by thermogenesis, which means dissipating energy in the form of heat. It is held that in mammals, long-term surplus food intake results in energy storage in the form of triglyceride and may eventually lead to obesity. Stimulating energy-dissipating function of brown adipose tissue in human body may counteract fat accumulation. In order to utilize brown adipose tissue as a therapeutic target, the mechanisms underlying brown adipocyte differentiation and function should be better elucidated. Here we review the molecular mechanisms involved in brown adipose tissue development and thermogenesis, and share our thoughts on current challenges and possible future therapeutic approaches.
Pyrosequencing of 16S rRNA gene amplicons to study the microbiota in the gastrointestinal tract of carp (Cyprinus carpio L.)
Authors: van Kessel Maartje AHJ , Dutilh Bas E , Neveling Kornelia , Kwint Michael P , Veltman Joris A , Flik Gert , Jetten Mike SM , Klaren Peter HM , Op den Camp Huub JM
Published: November 2011

The microbes in the gastrointestinal (GI) tract are of high importance for the health of the host. In this study, Roche 454 pyrosequencing was applied to a pooled set of different 16S rRNA gene amplicons obtained from GI content of common carp (Cyprinus carpio) to make an inventory of the diversity of the microbiota in the GI tract. Compared to other studies, our culture-independent investigation reveals an impressive diversity of the microbial flora of the carp GI tract. The major group of obtained sequences belonged to the phylum Fusobacteria. Bacteroidetes, Planctomycetes and Gammaproteobacteria were other well represented groups of micro-organisms. Verrucomicrobiae, Clostridia and Bacilli (the latter two belonging to the phylum Firmicutes) had fewer representatives among the analyzed sequences. Many of these bacteria might be of high physiological relevance for carp as these groups have been implicated in vitamin production, nitrogen cycling and (cellulose) fermentation.
Impact of grain-coating iron minerals on dielectric response of quartz sand and implications for ground-penetrating radar
Authors: Josh Matthew , Lintern Melvyn J. , Kepic Anton W. , Verrall Mike
Published: November 2011

An unexpected result of ground-penetrating radar (GPR) surveys in the Great Victoria Desert (South Australia) was the lack of returning signal in what appeared to be a favorable environment for GPR, with dry silica sand and calcrete aggregates in the near surface. We found that the dielectric response of the dry sand samples had much higher dielectric losses than comparable sands from Western Australia and that the dielectric losses are controlled by the presence of iron oxide minerals, although iron concentrations themselves are only around 0.4%. The samples contained over 90% quartz, with subsidiary amounts of carbonates, kaolin, and smectite occurring with the iron oxide minerals as a coating on the quartz grains. An acid washing procedure removed the reducible iron oxide minerals from the clay coating but left the clays substantially unaltered. Subsequent dielectric and magnetic analysis of the samples indicates that the iron oxide minerals removed during the washing process are responsible for the reduction of GPR penetration at 250 MHz from approximately 10 m to only 1 m.
Dynamic interactions of high Cdt1 and geminin levels regulate S phase in earlyXenopusembryos
Authors: Kisielewska Jolanta , Blow J. Julian
Published: November 2011

Cdt1 plays a key role in licensing DNA for replication. In the somatic cells of metazoans, both Cdt1 and its natural inhibitor geminin show reciprocal fluctuations in their protein levels owing to cell cycle-dependent proteolysis. Here, we show that the protein levels of Cdt1 and geminin are persistently high during the rapid cell cycles of the early Xenopus embryo. Immunoprecipitation of Cdt1 and geminin complexes, together with their cell cycle spatiotemporal dynamics, strongly supports the hypothesis that Cdt1 licensing activity is regulated by periodic interaction with geminin rather than its proteolysis. Overexpression of ectopic geminin slows down, but neither arrests early embryonic cell cycles nor affects endogenous geminin levels; apparent embryonic lethality is observed around 3-4 hours after mid-blastula transition. However, functional knockdown of geminin by ΔCdt1_193-447, which lacks licensing activity and degradation sequences, causes cell cycle arrest and DNA damage in affected cells. This contributes to subsequent developmental defects in treated embryos. Our results clearly show that rapidly proliferating early Xenopus embryonic cells are able to regulate replication licensing in the persistent presence of high levels of licensing proteins by relying on changing interactions between Cdt1 and geminin during the cell cycle, but not their degradation.
Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model
Authors: To Thuy Thanh , Witten P. Eckhard , Renn Joerg , Bhattacharya Dipanjan , Huysseune Ann , Winkler Christoph
Published: November 2011

Osteoclasts are macrophage-related bone resorbing cells of hematopoietic origin. Factors that regulate osteoclastogenesis are of great interest for investigating the pathology and treatment of bone diseases such as osteoporosis. In mammals, receptor activator of NF-κB ligand (Rankl) is a regulator of osteoclast formation and activation: its misexpression causes osteoclast stimulation and osteoporotic bone loss. Here, we report an osteoporotic phenotype that is induced by overexpression of Rankl in the medaka model. We generated transgenic medaka lines that express GFP under control of the cathepsin K promoter in osteoclasts starting at 12 days post-fertilization (dpf), or Rankl together with CFP under control of a bi-directional heat-shock promoter. Using long-term confocal time-lapse imaging of double and triple transgenic larvae, we monitored in vivo formation and activation of osteoclasts, as well as their interaction with osteoblasts. Upon Rankl induction, GFP-positive osteoclasts are first observed in the intervertebral regions and then quickly migrate to the surface of mineralized neural and haemal arches, as well as to the centra of the vertebral bodies. These osteoclasts are TRAP (tartrate-resistant acid phosphatase) and cathepsin K positive, mononuclear and highly mobile with dynamically extending protrusions. They are exclusively found in tight contact with mineralized matrix. Rankl-induced osteoclast formation resulted in severe degradation of the mineralized matrix in vertebral bodies and arches. In conclusion, our in vivo imaging approach confirms a conserved role of Rankl in osteoclastogenesis in teleost fish and provides new insight into the cellular interactions during bone resorption in an animal model that is useful for genetic and chemical screening.
Role of ST2 in Non–ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial
Authors: Kohli Payal , Bonaca Marc P , Kakkar Rahul , Kudinova Anastacia Y , Scirica Benjamin M , Sabatine Marc S , Murphy Sabina A , Braunwald Eugene , Lee Richard T , Morrow David A
Published: November 2011

OBJECTIVE

We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.

BACKGROUND

Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.

METHODS

We measured ST2 with a high-sensitivity assay in all available baseline samples (N = 4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non–ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.

RESULTS

Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P < 0.0001) and 1 year (12.2% vs 5.2%, P < 0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15–3.13 at 30 days, P = 0.012; 1.51, 95% CI 1.15–1.98 at 1 year, P = 0.003), with a significant integrated discrimination improvement (P < 0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction = 0.15).

CONCLUSIONS

ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.
Pindar und der „Protz“ Xenophon (fr. 122 M.). Von der Positionierung im politischen und im literarischen Feld
Authors: Stenger Jan
Published: November 2011

Pindar’s skolion for the Olympic victor Xenophon of Corinth (fr. 122) has received considerable attention for its subject rather than its poetic quality. For it celebrates a dedication of prostitutes to Aphrodite which scholars have considered a subject inappropriate for a choral ode. So they detected traces of a tension between the poet and Xenophon within the text. In this article it is argued that, quite the reverse, Pindar is drawing a parallel between himself and the victor and his family. If we reconsider the pragmatic aspects of the skolion, its relation to Olympian 13 and the context Athenaeus provides for the fragment, we are able to see that Pindar links sport, ritual and politics, thereby serving Xenophon’s ambitions as well as his own. By practising conspicuous consumption Xenophon aims at detaching himself from Corinth’s egalitarian aristocracy, and at the same time the poet promotes himself in the literary field as a poetic innovator and authority. So, both transgress expectations and boundaries.
“As I thought that the speakers most likely might have spoken”. Thukydides Hist. 1. 22. 1 on Composing Speeches
Authors: Schütrumpf Eckart
Published: November 2011

This paper addresses the scholarly controversies surrounding the succinct remark Thucydides makes at Hist. 1. 22. 1 on composing speeches. It argues for the understanding of the “ἂν εἰπεῖν” expression not as contrary-to-fact, as most scholars assume, but as potential of the past, to be translated: “as in his judgment the speakers most likely might have spoken.” The paper proposes that Thucydides indicates a historical method similar to the strategy used in contemporary rhetoric in order to show on the basis of probability considering all the conditions given that certain things were said. The paper scrutinizes every important term used by Thucydides at 1. 22. 1 (ἐδόκουν, τὰ δέοντα, ξύμπασα γνώμη) and the various modern interpretations and translations proposed.
Beobachtungen zu den Thukydidesscholien III. 3. Kodikologische Nachlese
Authors: Kleinlogel Alexander
Published: November 2011

Der Aufsatz ist die Fortsetzung von „Beobachtungen zu den Thukydidesscholien I“ (Philologus 108, 1964, 233–246) und „Beobachtungen zu den Thukydidesscholien II“ (Philologus 142, 1998, 11–40). Im ersten Abschnitt (3. 1) wird gezeigt, dass durch genauere Dokumentation der Marginalien im Vatic. gr. 126 (B), als es auch in neuen kritischen Ausgaben geschehen ist, mit unterschiedlicher Sicherheit abweichende Lesarten in Ω erschlossen werden können. In 3. 2 wird nachgewiesen, dass die Hand jenes Theodoros, der im Codex Paris. suppl. gr. 255 (A) eine vieldiskutierte Marginalnotiz eingetragen hat, auch – was bisher nicht beachtet worden ist – im Monac. graec. 430 (F) einen ähnlichen Marginaleintrag vorgenommen hat, woraus sich weitreichende Konsequenzen für eine Reihe von Handschriftenkomponenten ergeben. Die Identität jenes Theodoros lässt sich nicht ermitteln, die von Hemmerdinger vorgenommene Identitifikation mit Theodoros Metochites wird widerlegt. Abschnitt 3. 3 untersucht die Wolfenbütteler Handschrift Gud. gr. 35 (Gu) hinsichtlich ihrer Stellung im Stemma der Familie ψ und zeigt, dass Gu nicht zusammen mit μ2 und μ1 eine Abschrift von μ ist, sondern dass Gu selbst die Vorlage von μ2 und μ1 war, also mit μ identisch ist. Dadurch wird eine Vermutung D. Harlfingers bestätigt, dass der Codex Gu, der jetzt nur noch die Markellinosvita und die Anonymusvita des Thukydides enthält, der Rest einer kompletten Thukydideshandschrift ist. Da Gu der Schrift des Maximos Planudes bzw. der seiner Schreiber ähnelt, darf vermutet werden, dass im Gelehrtenkreis um Planudes eine Thukydidesausgabe geschaffen worden ist.
Meorum periculorum rationes utilitas rei publicae vincat. Zur Historizität der vierten Catilinaria
Authors: Martin Gunther
Published: November 2011

This paper proposes a reading of Cicero’s Fourth Catilinarian as a consistent and historically realistic attempt at urging the senate to punish the conspirators. Cicero struggles against the senators’ inclination to postpone a decision out of fear of the consequences which a severe sentence might have. The speech does not show signs of substantial revision or even contamination of several addresses Cicero made at different stages of the meeting on 5 December 63; nor may the extended passages in which Cicero talks about himself be read as subsequent additions in the light of Clodius’ assaults. They rather fit into the exhortative strategy of the speech, forming part of the refutation of any grounds which would allow for a delay of the decision. The extended space they take up is to be explained as a strategy that prevents further discussion of dangers by an argumentum a maiore.
Zum Autor der Schrift ,Über die Kriegsführung gegen die Parther‘
Authors: Schulze Christian
Published: November 2011

Johannes Lydos quotes a passage from a lost military work on warfare against the Parthers in De magistratibus 3, 34. The author of this work, which dates from 63 AD, is said to be Κέλσος ὁ Ῥωμαῖος τακτικός, who has repeatedly been identified as Marius Celsus in several research studies. This article, however, depicts the encyclopedist and medical practitioner Aulus Cornelius Celsus as the author of this military writing. It first provides a retrospective of the research done. Secondly it shows that two military writings are likely to exist in the works of Celsus and in a third step it puts forward a decisive argument against Marius Celsus. Finally, some further reflections on his interests and lifetime hint at Aulus Cornelius Celsus being the author.