bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathways of Change: Shifting Connectivities in the World City Network, 2000—08
Authors: Derudder Ben , Taylor Peter , Pengfei Ni  , De Vos Anneleen , Hoyler Michael , Hanssens Heidi , Bassens David , Jin Huang  , Witlox Frank , Wei Shen  , Xiaolan Yang
Published: July 2010

This is an empirical paper that measures and interprets changes in intercity relations at the global scale in the period 2000—08. It draws on the network model devised by the Globalization and World Cities (GaWC) research group to measure global connectivities for 132 cities across the world in 2000 and 2008. The measurements for both years are adjusted so that a coherent set of services/cities is used. A range of statistical techniques is used to explore these changes at the city level and the regional scale. The most notable changes are: the general rise of connectivity in the world city network; the loss of global connectivity of US and sub-Saharan African cities (Los Angeles, San Francisco and Miami in particular); and, the gain in global connectivity of south Asian, Chinese and eastern European cities (Shanghai, Beijing and Moscow in particular).
Economic Globalisation and the Structure of the World City System: The Case of Airline Passenger Data
Authors: Mahutga Matthew C. , Xiulian Ma  , Smith David A. , Timberlake Michael
Published: July 2010

This paper reports results from an analysis of the relationship between the structure of the city-to-city network of global airline passenger flows and the interstate world system. While many scholars suggest that the broader parameters of the world system structure the urban hierarchy embedded within or articulated to it, others argue that the urban hierarchy is decoupling from the world system. The analyses show that there has been some modest convergence in the distribution of power in the world city system. Moreover, they suggest that the mechanism for this convergence is the upward mobility of cities located in the semi-periphery and the east Asian region. The paper closes by considering the implication of these findings for a larger understanding of the relationship between globalisation, the structure of the world city system and its articulation with the world system.
The Geography of Internet Infrastructure: An Evolutionary Simulation Approach Based on Preferential Attachment
Authors: Vinciguerra Sandra , Frenken Koen , Valente Marco
Published: July 2010

In this paper, the evolution of infrastructure networks is modelled as a preferential attachment process. It is assumed that geographical distance and country borders provide barriers to link formation in infrastructure networks. The model is validated against empirical data on the European Internet infrastructure network covering 209 cities. The average path length and average clustering coefficient of the observed network are successfully simulated. Furthermore, the simulated network shows a significant correlation with the observed European Internet infrastructure network. The paper ends with a discussion on the future uses of preferential attachment models in the light of the literature on world cities and global cities.
Routes to Positive Interracial Interactions: Approaching Egalitarianism or Avoiding Prejudice
Authors: Plant E. Ashby , Devine Patricia G. , Peruche Michelle B.
Published: July 2010

The current work examined factors that contribute to positive interracial interactions. It argues that the source of people’s motivation to respond without prejudice and the goals and strategies they pursue in interracial interactions influence the quality of these interactions. Three studies show that non-Black participants who are highly internally motivated to respond without prejudice tend to focus on strategies and behaviors in interactions with Black people that approach a positive (i.e., egalitarian) outcome. As a result of engaging in these approach behaviors, their interracial interactions go more smoothly for both themselves and their interaction partners as compared to people less internally motivated. In contrast, externally motivated people tend to focus on avoiding negative (i.e., prejudiced) outcomes, which ironically results in their coming across to their partners as prejudiced. The implications of the findings for smoothing out the rocky road to positive intergroup interactions are discussed.
Necessary for Possession: How People Reason About the Acquisition of Ownership
Authors: Friedman Ori
Published: July 2010

For property rights to be upheld, people need to be able to judge how ownership is established. Previous research suggests that people may judge that the first person to possess an object establishes ownership over it. This article proposes and tests an alternative account, which claims that people decide who owns an object by judging who was probably necessary for the object to be possessed. Participants read stories in which one character pursues an object (e.g., an animal being hunted, a gem jutting out of a high cliff), which a second character then captures. Judgments about which character owns the object depended on which character was plausibly necessary for capturing the object. The findings support the “necessary for possession” account and suggest that people’s judgments about ownership likely depend on counterfactual reasoning or on processes akin to those used to make judgments about causality.
Too Good to Be True? Understanding Change in Organizational Outcomes
Authors: Nye Christopher D. , Brummel Bradley J. , Drasgow Fritz
Published: July 2010

When evaluating organizational outcomes, strong experimental designs are often not practical. As a result, assessments of change may be confounded by a number of threats to their validity. Therefore, attempts have been made to detect or control for many of these artifacts. This article explores a method for detecting response artifacts, using measurement and relational equivalence techniques. The large drop in the reported levels of sexual harassment in the U.S. military between 1995 and 2002 provides the context for testing this method. The results suggest that at least part of the reported decrease in harassment was artifactual. The implications for evaluations of organizational change are discussed.
Enumeration and the Linguistic Identity Formation in Colonial North India
Authors: Sarangi Asha
Published: July 2010

A number of enumerative practices and discourses were instrumental in defining the politics of linguistic codification, quantification and gradually the shaping of the linguistic identity formation of various communities and groups in colonial north India. The British colonial state systematically pursued the ‘logic of numbers’ through regular census operations, data release in gazetteers, and linguistic survey reports and records of various kinds to standardize and construct new modes of ‘disciplining’ the linguistic diversity and its communicative rationale. It is important to critically engage with this genre of enumerative writings to further understand the politics of identity con-struction based on language in its dialogical relationship with other social categories of religion, caste, region, gender and class, etc.
Analytic Reviews: Managing the Agitated Patient in the ICU: Sedation, Analgesia, and Neuromuscular Blockade
Authors: Honiden Shyoko , Siegel Mark D.
Published: July 2010

Physical and psychological distress is exceedingly common among critically ill patients and manifests generically as agitation. The dangers of over- and undertreatment of agitation have been well described, and the intensive care unit (ICU) physician must strike a balance in the fast-paced, dynamic ICU environment. Identification of common reversible etiologies for distress may obviate the need for pharmacologic therapy, but most patients receive some combination of sedative, analgesic, and neuroleptic medications during the course of their critical illness. As such, understanding key pharmacologic features of commonly used agents is critical. Structured protocols and objective assessment tools can optimize drug delivery and may ultimately improve patient outcomes by reducing ventilator days, ICU length of stay, and by reducing cognitive dysfunction.
From Charity to Caring
Authors: Selanders Louise C. , Lake Karen , Crane Patrick
Published: July 2010

Florence Nightingale has been the subject of numerous biographies and topical studies since she became a public figure during the Crimean War of 1854-1856. However, both the biographical and the topical literature have given little emphasis to the fourteen months of Nightingale’s superintendency at The Establishment for Gentlewomen During Illness located on Harley Street, London. Thematic analysis of primary documents including Nightingale’s Quarterly Reports to the Governors of her Nursing Home and the recently identified found Minutes of the Ladies’ Committee of the Establishment of Gentlewomen During Illness were utilized to identify specific themes considered essential to Nightingale’s professional and philosophical development. Harley Street proved to be the catalyst of opportunity that later launched her into the public view as a visionary through which she was to develop nursing as a profession and promote nursing as a legitimate route for women’s education and employment.
The Economic Value of Volunteer Work
Authors: Sajardo Antonia , Serra Inmaculada
Published: July 2010

Despite the socioeconomic interest that is associated with volunteer work, the practice of valuing it is limited, and few scientific advances have been made. In this context, this study first analyses why these advances are scarce, paying special attention to the limitations of micro- and macro-accounting systems, including volunteer work accounts. It then proposes a method with heuristic capacity for valuing the various economic dimensions of volunteer work. The third part of this article applies this proposal to social and environmental volunteer work in the Spanish region of Valencia. The conclusions bring to focus the fact that whereas the technical obstacles faced in conducting empirical analysis are not insurmountable, obstacles of a sociopolitical nature and of scientific mindsets continue to hinder the advance of research in this field of the social sciences.
Organ economy: organ trafficking in Moldova and Israel
Authors: Lundin Susanne
Published: July 2010

Organ trafficking is an illegal means of meeting the shortage of transplants. The activity flourishes for several interacting reasons, such as medical needs, poverty and criminality. Other factors are fundamental conceptual structures such as the dream of the regenerative body as well as the view of the body as an object of utility and an object of value. The article aims to go behind the normative discussions that usually surround organ trafficking. Why this is happening, and what the societal consequences are, is examined through ethnographic fieldwork. The focus is on the shadow economies that govern existence and in which people, goods, weapons, money, bodies, etc. constitute components of the global market.
Teaching Management in the Slovak Republic: Lessons Learned and Encouragement for Potential Fulbright Scholars
Authors: Meyer-Emerick Nancy
Published: July 2010

This story of a Fulbright scholar’s experience is designed to help future Fulbrighters and those interested in teaching in more culturally diverse environments. Although each Fulbright teaching experience is unique, the majority of challenging situations can be resolved by adequate preparation before the assignment and by the willingness to be flexible once abroad. This article provides guidance for those contemplating applying for a Fulbright, preparing to teach abroad, living and teaching in another culture, and strategies for teaching cross-cultural competence without going abroad.
Predicting Values and Beliefs: Learning That Can Last
Authors: Chavez Carolyn I. , Ferris William P. , Gibson Lindsey A.
Published: July 2010

The authors developed this experiential exercise to aid students in learning how others perceive them as well as how they perceive others and, ultimately, to begin to help them identify the origins of such perceptions. The exercise’s goal is to explore how participants may make inaccurate perceptions of others and how they might pierce through these misperceptions to develop a new way of valuing others. Ultimately, it seeks to help learners identify common biases such as confirmation/disconfirmation bias, stereotyping, projection, and halo effects and to practice active, nonjudgmental listening and empathy as well as receptivity to differences they may have with others. It is especially useful as a structured student experience when studying perception and individual differences in organizational behavior classes, in some of which the authors have used it multiple times. They have also used different iterations to open conferences, as an icebreaker, in executive training, and in self-development courses. Detailed instructions, description of the authors’ debriefing experiences, and student evaluations are provided.
General Model for Molecular Interactions in a Benzene Dimer
Authors: Tran-Duc Thien , Thamwattana Ngamta , Cox Barry J. , Hill James M.
Published: July 2010

Modelling molecular interactions in a benzene dimer is a typical example of a class of problems involving aromatic molecules. Although many studies on the benzene dimer have been carried out both theoretically and experimentally and energetically favorable structures of a benzene dimer have been found, an investigation of all equilibrium structures of a benzene dimer has not so far been done. Previously, the present authors investigated the interaction energy and geometries of a benzene dimer for the special case in which only one rotational angle is used to describe the relative position between two benzene molecules. In general, two rotational angles are necessary to describe the most general relative orientation. Here, we apply the same approach in which the discrete atomic structure of a benzene molecule is replaced by two continuous rings of atoms, namely an inner carbon ring and an outer hydrogen ring with average constant atomic densities and the molecular interaction forces are calculated from the Lennard-Jones potential function. An analytical expression for the interaction energy is obtained which we use to determine all equilibrium structures of a benzene dimer as well as to determine those domains in which certain configurations are more favorable than others. Our results show that parallel, T-shaped, parallel displaced and tilted structures are all possible configurations of a benzene dimer and they exist at different regions of vertical and offset distances at different energy levels.
Adaptive-Compi: Enhancing Mpi-Based Applications’ Performance and Scalability by using Adaptive Compression
Authors: Filgueira Rosa , Singh David E. , Carretero Jesús , Calderón Alejandro , García Félix
Published: July 2010

This paper presents an optimization of MPI communication, called Adaptive-CoMPI, based on runtime compression of MPI messages exchanged by applications. The technique developed can be used for any application, because its implementation is transparent for the user, and integrates different compression algorithms for both MPI collective and point-to-point primitives. Furthermore, compression is turned on and off and the most appropriate compression algorithms are selected at runtime, depending on the characteristics of each message, the network behavior, and compression algorithm behavior, following a runtime adaptive strategy. Our system can be optimized for a specific application, through a guided strategy, to reduce the runtime strategy overhead. Adaptive-CoMPI has been validated using several MPI benchmarks and real HPC applications. Results show that, in most cases, by using adaptive compression, communication time is reduced, enhancing application performance and scalability.
Review: The antidepressant agomelatine improves the quality of life of depressed patients: implications for remission
Authors: Llorca Pierre-Michel
Published: July 2010

One of the ongoing clinical challenges associated with the management of major depressive disorder is the fact that many patients do not achieve complete remission and even fewer patients remain in remission. Residual symptoms and poor treatment adherence are two of the main risk factors for relapse with current therapies. In order to face these challenges, clinicians need new treatment strategies that can provide more sustained, longer-term efficacy and adherence. Agomelatine, an innovative antidepressant, is a melatonergic MT1/MT2 agonist with 5HT2C receptor antagonist activity. Randomized, controlled studies have shown that agomelatine reduces depression symptoms and is well tolerated during short-term and long-term treatment strategies. Low relapse rates (21.7% for agomelatine versus 46.6% for placebo after 6 months of continuation treatment; p < 0.0001) have been reported and are believed to be the result of the cumulative effect of agomelatine at all stages of depression. In particular, specific residual symptoms, such as anxiety and sleep disturbances, which increase the rate of relapse, are significantly improved with agomelatine treatment. Furthermore, quality of life during remission, which can affect adherence rates, is likely to be improved because sexual function and weight are preserved. The combination of these unique properties suggests that treatment with agomelatine will provide more sustained, longer-term remission because antidepressant efficacy is combined with fewer residual symptoms and better tolerability and adherence.
Review: The importance of early symptom relief in antidepressant treatment: focus on agomelatine
Authors: Lam Raymond W
Published: July 2010

Antidepressants were traditionally considered to have delayed onset of action, and clinical opinion often stated that patients may not experience noticeable improvement for 4—6 weeks. Recent studies have shown, however, that antidepressants have more rapid onset of effect, within 1—2 weeks, and that this early response may be associated with later sustained response. Moreover, there is emerging evidence that some medications may have faster onset of therapeutic effect than others. The new antidepressant agomelatine, with its novel pharmacological profile as an agonist at melatonergic (MT1 and MT2) receptors and antagonist at 5-HT2C receptors, has in several studies produced earlier symptom improvement than comparator selective serotonin reuptake inhibitors and serotonin—noradrenaline reuptake inhibitors. In particular, beneficial effects on sleep and daytime functioning are noticeable as early as the first week of treatment. These therapeutic benefits may, in part, be related to its regulatory effects on circadian and sleep— wake cycles. Agomelatine therefore combines early symptom relief with a favorable side-effect profile and short-term and long-term antidepressant efficacy. These properties suggest that agomelatine can be considered a first-line treatment for patients with major depression.
Review: Clock genes at the heart of depression
Authors: Kennaway David J
Published: July 2010

The rhythms of life are ever pervasive, touching almost every aspect of our lives. We are finely tuned to the cycle of light and dark, so that we normally sleep during the night and are active during the day. Physiological rhythms are, however, not just slaves to the solar day, but are actually generated endogenously within the suprachiasmatic nuclei in the hypothalamus and are entrained via the retina. The circadian timing system is organized hierarchically with the suprachiasmatic nuclei providing neural and/or hormonal cues to the various organ systems, allowing them to express their own rhythmic physiological output. There is now a substantial body of evidence emerging that disruption of rhythmicity through altered sleep/wake patterns and exposure to light, or through endogenous disruption of key determinants of endogenous rhythms, can be detrimental to health. Circadian rhythm disturbances have long been associated with mood disorders, especially delayed sleep onset, and evidence is accumulating that alterations to the cellular timing system may underpin some aspects of the disorders. For example, mice carrying mutations in either Clock or per2 spend less time immobile in swim tests, which has been suggested as mimicking mania. In humans, single nucleotide polymorphisms in Clock and other clock genes have been associated with depression. With this increasing knowledge we may predict that new antidepressant drugs will emerge that, as a primary or secondary mechanism of action, target and correct abnormalities in the circadian timing system.
Review: Restoring circadian rhythms: a new way to successfully manage depression
Authors: Gorwood Philip
Published: July 2010

For many patients suffering from major depressive disorder, available treatments are unsatisfactory due to long delays before the onset of effects, low response rates, poor tolerability, and high recurrence rates. Evidence now suggests that major depressive disorder is a complex syndrome fed by multiple pathways and therefore that modulating serotonergic and noradrenergic neurotransmission, while important, is insufficient. To this effect, data have shown consistently over the last 50 years that patients suffering from depression experience a wide range of circadian rhythm disturbances, and that temporary remission of symptoms can be reached with chronotherapeutic interventions. Agomelatine, a melatonergic antidepressant with an innovative pharmacological profile, is both a melatonergic receptor agonist and a 5HT2C receptor antagonist. Its antidepressant activity has been demonstrated in animal models and placebo-controlled trials as well as in comparator studies. Clinically and statistically significant improvements in the core symptoms of depression, as well as a rapid onset of benefits, low relapse rates upon discontinuation, and high tolerability have been noted. It is likely that the antidepressant activity of agomelatine results, at least in part, from the resynchronization of the circadian rhythms that are disturbed in many depressed patients. In a recent study, for example, treatment with agomelatine significantly improved the amplitude of the circadian rest—activity/ sleep—wake cycle and decreased depression and anxiety symptoms compared with treatment with sertraline. Together, these data suggest that agomelatine, through its innovative mechanism of action, may result in a more complete and sustained remission for chronically depressed patients.
Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension
Authors: Enseleit Frank , Lüscher Thomas F. , Ruschitzka Frank
Published: July 2010

Resistant hypertension is defined as failure to lower blood pressure to target when a patient adheres to the maximum tolerated doses of three antihypertensive drugs including a diuretic. Notwithstanding the wide availability of several antihypertensive agents and the continued recommendation of dietary and lifestyle modifications, the prevalence of resistant hypertension remains high and is expected to increase thus underscoring the need for potential new treatment modalities in resistant hypertension. Endothelin-1 is a long-lasting potent vasoconstrictor and plays a key role in cardiovascular haemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension are reviewed. The leading journals that publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. While results from early clinical studies suggested that darusentan might emerge as new treatment option in patients with resistant hypertension, results from recent studies suggests that darusentan appears unlikely to find its way in the armamentarium for treatment of resistant hypertension.
The International Two-Step Flow in Foreign News: Canadian and U.S. Television News Coverage of U.S. Affairs
Authors: Farnsworth Stephen , Soroka Stuart , Young Lori
Published: July 2010

Content analysis of U.S. and Canadian television news from 2004 to 2006 reveals considerable similarities in the volume of news coverage of President George W. Bush and the Iraq War on both sides of the border. Indeed, these data suggest the possibility of an international two-step news flow, where changes in the volume of coverage on NBC frequently were reflected in the news coverage on CBC and CTV during the following days. It is suggested here that this may be attributable to the limitations faced by international reporters, resulting in a “two-step flow” that should be relevant not just for Canadian reporters in the United States, but also for many international reporters elsewhere.
An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas
Authors: Pham Lan V. , Tamayo Archito T. , Li Changping , Bueso-Ramos Carlos , Ford Richard J.
Published: July 2010

The nuclear factor of activated T cells (NFAT) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for cell growth and survival in hematopoietic cells. Recent experimental evidence has implicated the calcineurin/NFAT signaling pathway in the pathogenesis of various malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the molecular mechanism(s) underlying NFATc1 regulation of genes controlling lymphoma cell growth and survival is still unclear. In this study, we demonstrate that the transcription factor NFATc1 regulates gene expression in DLBCL cells through a chromatin remodeling mechanism that involves recruitment of the SWItch/Sucrose NonFermentable chromatin remodeling complex ATPase enzyme SMARCA4 (also known as Brahma-related gene 1) to NFATc1 targeted gene promoters. The NFATc1/Brahma-related gene 1 complex induces promoter DNase I hypersensitive sites and recruits other transcription factors to the active chromatin site to regulate gene transcription. Targeting NFATc1 with specific small hairpin RNA inhibits DNase I hypersensitive site formation and down-regulates target gene expression. Our data support a novel epigenetic control mechanism for the transcriptional regulation of growth and survival genes by NFATc1 in the pathophysiology of DLBCL and suggests that targeting NFATc1 could potentially have therapeutic value.
Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington's disease
Authors: Sari Youssef , Prieto Anne L , Barton Scott J , Miller Benjamin R , Rebec George V
Published: July 2010

Background

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a β-lactam antibiotic that increases GLT1 expression. Only at advanced ages (> 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s.

Results

Western blots were used to assess GLT1 expression in both striatum and cerebral cortex in R6/2 and corresponding wild-type (WT) mice at 9 and 13 weeks of age. Mice were euthanized for immunoblotting 24 hr after five consecutive days of once daily injections (ip) of ceftriaxone (200 mg/kg) or saline vehicle. Despite a significant GLT1 reduction in saline-treated R6/2 mice relative to WT at 13, but not 9, weeks of age, ceftriaxone treatment increased cortical and striatal GLT1 expression relative to saline in all tested mice.

Conclusions

The ability of ceftriaxone to up-regulate GLT1 in R6/2 mice at an age when GLT1 expression is significantly reduced suggests that the mechanism for increasing GLT1 expression is still functional. Thus, ceftriaxone could be effective in modulating glutamate transmission even in late-stage HD.
CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies
Authors: Nakamura Yoji , Komiyama Tomoyoshi , Furue Motoki , Gojobori Takashi , Akiyama Yasuto
Published: July 2010

Background

Immunoglobulin (IG or antibody) and the T-cell receptor (TR) are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]).

Description

This database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I) and 1,470 on hematological tumors (Group II). Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration athttp://www.scchr-cigdb.jp/, and the search results are freely downloadable.

Conclusions

The CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting annotation on IG, TR, and their epitopes. This database contains IG and TR data classified into two cancer-related groups and is able to automatically classify accumulating entries into these groups. The entries in Group I are particularly crucial for cancer immunotherapy, providing supportive information for genetic engineering of novel antibody medicines, tumor-specific TR, and peptide vaccines.
Global transcriptome profiling of wild soybean (Glycine soja) roots under NaHCO3treatment
Authors: Ge Ying , Li Yong , Zhu Yan-Ming , Bai Xi , Lv De-Kang , Guo Dianjing , Ji Wei , Cai Hua
Published: July 2010

Background

Plant roots are the primary site of perception and injury for saline-alkaline stress. The current knowledge of saline-alkaline stress transcriptome is mostly focused on saline (NaCl) stress and only limited information on alkaline (NaHCO3) stress is available.

Results

Using Affymetrix® Soybean GeneChip®, we conducted transcriptional profiling on Glycine soja roots subjected to 50 mmol/L NaHCO3 treatment. In a total of 7088 probe sets, 3307 were up-regulated and 5720 were down-regulated at various time points. The number of significantly stress regulated genes increased dramatically after 3 h stress treatment and peaked at 6 h. GO enrichment test revealed that most of the differentially expressed genes were involved in signal transduction, energy, transcription, secondary metabolism, transporter, disease and defence response. We also detected 11 microRNAs regulated by NaHCO3 stress.

Conclusions

This is the first comprehensive wild soybean root transcriptome analysis under alkaline stress. These analyses have identified an inventory of genes with altered expression regulated by alkaline stress. The data extend the current understanding of wild soybean alkali stress response by providing a set of robustly selected, differentially expressed genes for further investigation.
Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery
Authors: Abdelmalak Basem , Maheshwari Ankit , Mascha Edward , Srivastava Sunita , Marks Theodore , Tang WH Wilson , Kurz Andrea , Sessler Daniel I
Published: July 2010

Background

The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia.

Methods/Design

The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment.

Discussion

The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three.

Trial registration

This trial is registered at Clinicaltrials.gov #: NTC00433251
Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions
Authors: Shiraishi Takehiko , Eysturskarð Jonhard , Nielsen Peter E
Published: July 2010

Background

Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human cancer gene in JAR cells.

Methods

We screened 10 different 15 mer PNAs targeting intron2 at both the 5' - and the 3'-splice site for their effects on the splicing of mdm2 using RT-PCR analysis. We also tested a PNA (2512) targeting the 3'-splice site of intron3 with a complementarity of 4 bases to intron3 and 11 bases to exon4 for its splicing modulation effect. This PNA2512 was further tested for the effects on the mdm2 protein level as well as for inhibition of cell growth in combination with the DNA damaging agent camptothecin (CPT).

Results

We show that several of these PNAs effectively inhibit the splicing thereby producing a larger mRNA still containing intron2, while skipping of exon3 was not observed by any of these PNAs. The most effective PNA (PNA2406) targeting the 3'-splice site of intron2 had a complementarity of 4 bases to intron2 and 11 bases to exon3. PNA (2512) targeting the 3'-splice site of intron3 induced both splicing inhibition (intron3 skipping) and skipping of exon4. Furthermore, treatment of JAR cells with this PNA resulted in a reduction in the level of MDM2 protein and a concomitant increase in the level of tumor suppressor p53. In addition, a combination of this PNA with CPT inhibited cell growth more than CPT alone.

Conclusion

We have identified several PNAs targeting the 5'- or 3'-splice sites in intron2 or the 3'-splice site of intron3 of mdm2 pre-mRNA which can inhibit splicing. Antisense targeting of splice junctions of mdm2 pre-mRNA may be a powerful method to evaluate the cellular function of MDM2 splice variants as well as a promising approach for discovery of mdm2 targeted anticancer drugs.
Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia
Authors: Youn You-Sook , Lee Kyung-Yil , Hwang Ja-Young , Rhim Jung-Woo , Kang Jin-Han , Lee Joon-Sung , Kim Ji-Chang
Published: July 2010

Background

M. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns.

Methods

The diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients).

Results

Eighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge.

Conclusions

In MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.
Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells
Authors: Tang Rining , Li Qing , Lv Linli , Dai Houyong , Zheng Min , Ma Kunling , Liu Bicheng
Published: July 2010

Background

Substantial evidence suggests that high glucose (HG) causes endothelial cell damage; however, the potential mechanism therein has yet to be clarified. The aim of this study was to investigate the influence of HG on the endothelial-to-mesenchymal transition (EndMT) and its relevance to the activation of the renin-angiotensin system.

Methods

Primary human aortic endothelial cells (HAECs) were divided into three groups: a normal glucose (NG) group, HG group, and irbesartan (1 μM)-treated (HG+irbesartan) group. The concentration of angiotensin II in the supernatant was detected by radioimmunoassay. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of CD31 and fibroblast markers, such as fibroblast-specific protein 1 (FSP1). The expressions of FSP1 and α-SMA were detected by RT-PCR and Western blot.

Results

The treatment of HAECs in the HG group resulted in significant increases in the expressions of FSP1 and angiotensin II in dose-and time-dependent manners. The incubation of HAECs exposure to HG resulted in a fibroblast-like phenotype, wherein increased microfilamentation and a roughened endoplasmic reticulum structure were observed in the cytoplasm. The expressions of FSP1 and α-SMA were significantly increased in the HG group, and these changes were inhibited by irbesartan treatment (P < 0.05). Double staining of the HAECs indicated a co-localization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining; however, treatment with irbesartan attenuated the expression of EndMT (P < 0.05).

Conclusions

These findings suggest a novel mechanism in HG-induced endothelial damage via the mediation of the EndMT by angiotensin II, which was inhibited by Irbesartan.
First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia
Authors: Tang Thuy-Huong Ta , Salas Ana , Ali-Tammam Marwa , Martínez María del Carmen , Lanza Marta , Arroyo Eduardo , Rubio Jose Miguel
Published: July 2010

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old.
Plasmodium falciparum parasites causing cerebral malaria share variant surface antigens, but are they specific?
Authors: Kheliouen Nabila , Viwami Firmine , Lalya Francis , Tuikue-Ndam Nicaise , Moukoko Else C Eboumbou , Rogier Christophe , Deloron Philippe , Aubouy Agnès
Published: July 2010

Background

Variant surface antigens (VSA) expressed on the surface of Plasmodium falciparum-infected red blood cells constitute a key for parasite sequestration and immune evasion. In distinct malaria pathologies, such as placental malaria, specific antibody response against VSA provides protection. This study investigated the antibody response specifically directed against VSA expressed by parasites isolated from individuals presenting a given type of clinical presentation.

Methods

Plasma and isolates were obtained from four groups of Beninese subjects: healthy adults, patients presenting uncomplicated malaria (UM), cerebral malaria (CM), or pregnancy-associated malaria (PAM). The reactivity of plasma samples from each clinical group was measured by flow cytometry against parasites isolated from individuals from each clinical group.

Results

Antibody responses against VSAUM were predominant in CM, UM and HA plasmas. When analysed according to age in all plasma groups, anti-VSACM and -VSAUM antibody levels were similar until six years of age. In older groups (6-18 and >19 years of age), VSAUM antibody levels were higher than VSACM antibody levels (P = .01, P = .0008, respectively). Mean MFI values, measured in all plasmas groups except the PAM plasmas, remained low for anti-VSAPAM antibodies and did not vary with age. One month after infection the level of anti-VSA antibodies able to recognize heterologous VSACM variants was increased in CM patients. In UM patients, antibody levels directed against heterologous VSAUM were similar, both during the infection and one month later.

Conclusions

In conclusion, this study suggests the existence of serologically distinct VSACM and VSAUM. CM isolates were shown to share common epitopes. Specific antibody response to VSAUM was predominant, suggesting a relative low diversity of VSAUM in the study area.
MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation
Authors: Yu Jun , Ohuchida Kenoki , Mizumoto Kazuhiro , Sato Norihiro , Kayashima Tadashi , Fujita Hayato , Nakata Kouhei , Tanaka Masao
Published: July 2010

Background

Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of miR-200c has been shown to be associated with upregulating the expression of E-cadherin, a gene known to be involved in pancreatic cancer behavior. However, the significance of miR-200c in pancreatic cancer is unknown.

Methods

In the present study, we investigated the relationship between E-cadherin and miR-200c expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of miR-200c on the proliferation and invasion of pancreatic cancer cells.

Results

We found that patients with high levels of miR-200c expression had significantly better survival rates than those with low levels of miR-200c expression. We also found a remarkably strong correlation between the levels of miR-200c and E-cadherin expression.

Conclusions

These data indicate that miR-200c may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.