bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic Balance: Race against the tide
Authors: Harker Joseph
Published: April 2008

Harker, assistant comment editor at The Guardian, argues that progress towards proper ethnic diversified staffs within the media - the press, especially - has been slow. The number of racial minorities in editing positions across all Fleet Street is tiny, he claims, and most of the main desks on the nationals - home, foreign, city, features, sports - are run by entirely white teams. Harker concludes: 'As newspapers face more and more intense competition, both in print and online, surely they can't afford to ignore Britain's growing minority population. The assumption that things can continue as they always have, with a wealthy well-connected elite handing down news from above, expecting their underlings to try to imitate them, just doesn't fit our 21st century profile. Ultimately, what surely we all want is for all sections of society to feel they are properly represented in the range, variety and balance of stories written about them... But how many newspaper organisations will genuinely commit themselves to reaching that goal?'
Rogue elephant
Authors: Whitwell Tom
Published: April 2008

A new breed of editors has emerged with the development of web journalism. Tom Whitwell, communities editor of Times Online, is one of them and here describes life in the fast lane of the information super highway. He writes: "Traditional [media] power structures are unlikely to last for very much longer. I've never been a staff newspaper journalist, but I've always understood it to be a hierarchical, politically charged operation, where questions of right and wrong are answered by seniority. The online world is still as political as any office, but there's an elephant in the room that can't be ignored for long: In print, you often have no real idea what sells your newspaper. Online, you know exactly what's selling your site, live, 24 hours a day. So the editor can certainly pay his old school chum to write a jolly column about nothing much in particular. But it will be immediately obvious if nobody much in particular is reading it. Similarly, a youngster toiling in an unfashionable backwater who works hard and promotes his or her stuff online can find an audience. It doesn't matter that it's never promoted on the homepage, because traffic can be found elsewhere - from blogs or news aggregators or Google searches."
Truth values and truth-commitment in interdiscursive dating ads
Authors: Marley Carol
Published: April 2008

In this article, I explore issues of commitment to truth in dating ads that use apparently impossible categorizations to project identities for ad writers and their desired others. The article begins with a brief overview of relevant aspects of Text World Theory (especially Gavins's work on dating ads), Sinclair's model of fictional worlds and Routledge and Chapman's account of truth-commitment in discourse, and proposes the need for a framework that allows for a partial suspension of commitment to truth. I then draw on the work of Ivanič and Weldon on identity in writing, in order to develop an account that offers a discourse- and genre-based discussion of how the intertextual metaphors in such ads are interpreted in relation to truth values. I suggest the default stance is that of positive commitment to literal truth and that, when this is not possible, a fall-back mode of negative commitment to metaphorical truth is preferred over an interpretation in which questions of truth are truly suspended. Finally, I consider a related category, of apparently negative dating ad identities, in order to suggest a functional motivation for the inclusion of elements that cannot be interpreted in truth-committed mode.
Autonomy and Advocacy in Perinatal Nursing Practice
Authors: Simmonds Anne H
Published: April 2008

Advocacy has been positioned as an ideal within the practice of nursing, with national guidelines and professional standards obliging nurses to respect patients' autonomous choices and to act as their advocates. However, the meaning of advocacy and autonomy is not well defined or understood, leading to uncertainty regarding what is required, expected and feasible for nurses in clinical practice. In this article, a feminist ethics perspective is used to examine how moral responsibilities are enacted in the perinatal nurse—patient relationship and to explore the interaction between the various threads that influence, and are in turn affected by, this relationship. This perspective allows for consideration of contextual and relational factors that impact on the way perinatal nursing care is given and received, and provides a framework for exploring the ways in which patient autonomy, advocacy and choice are experienced by childbearing women and their nurses during labour and birth.
Just Green Iguanas?
Authors: Sementelli Arthur , Smith Henry T. , Meshaka Walter E. , Engeman Richard M.
Published: April 2008

Invasive exotic species have begun to emerge as a policy issue at the federal, state, and local levels. Although invasive species are often understood as a function of the damage they cause to localized ecosystems, this study diverges by discussing the infrastructural damage caused by an invasive exotic species, the green iguana ( Iguana iguana). Specifically, the authors discuss the magnitude and scope of damage caused by iguana burrows on canals in southern Florida and offer policy recommendations to move discussions of this potentially disastrous public works issue forward.
Integrating Adult Learning Principles Into Training for Public Health Practice
Authors: Bryan Rebecca L. , Kreuter Matthew W. , Brownson Ross C.
Published: April 2008

Providing training and planned learning experiences to practitioners and community partners is fundamental to effective public health. The extent to which principles of adult learning currently guide such training is unknown and likely varies widely. The purpose of this article is to introduce five principles of adult learning and discuss how each can be applied in assessing trainee needs, planning and delivering training, and evaluating training processes and outcomes. Training guided by these principles should facilitate adult learning, collaborative efforts, and mutual respect between agencies, practitioners, and community partners.
Are asymptomatic airway hyperresponsiveness and allergy risk factors for asthma? A longitudinal study
Authors: van den Nieuwenhof L. , Schermer T. , Heijdra Y. , Bottema B. , Akkermans R. , Folgering H. , van Weel C.
Published: April 2008

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but it is unclear whether asymptomatic AHR is associated with a higher risk of asthma. The present study assessed whether there is an association between asymptomatic AHR in adolescence and asthma in adulthood. The association between allergy and development of asthma was also investigated.

A follow-up study of a general population cohort of adolescents was performed 14 yrs after baseline. Respiratory status was assessed at baseline in 1989 and at follow-up in 2003–2004 by a respiratory symptoms questionnaire, spirometry and histamine challenge. Allergy status was also assessed.

The respiratory status of 199 subjects was assessed twice. In total, 91 (46%) subjects had the same AHR status in combination with respiratory symptoms at follow-up as at baseline. Adjusted for age, sex, allergy, family history of asthma and smoking history, having asymptomatic AHR was not significantly related to having asthma 14 yrs later (odds ratio (OR) 2.15, 95% confidence interval (CI) 0.67–6.83). For subjects with allergy at baseline, the OR for developing asthma was 4.45 (95% CI 1.46–13.54).

Screening for asymptomatic airway hyperresponsiveness in adolescence does not identify subjects at risk of developing asthma. Conversely, the presence of allergy in adolescence does seem to be a risk factor for asthma development.
Asbestos induces doxorubicin resistance in MM98 mesothelioma cellsviaHIF-1α
Authors: Riganti C. , Doublier S. , Aldieri E. , Orecchia S. , Betta P. G. , Gazzano E. , Ghigo D. , Bosia A.
Published: April 2008

Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1α, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1α and an increased expression of Pgp.

After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1α activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect.

Crocidolite, dexrazoxane and hypoxia caused HIF-1α activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1.

Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1α activity, through an iron-sensitive mechanism.
Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure
Authors: Shovlin C. L. , Tighe H. C. , Davies R. J. , Gibbs J. S. R. , Jackson J. E.
Published: April 2008

Increasing evidence supports the use of embolisation to treat pulmonary arteriovenous malformations (AVMs). Most pulmonary AVM patients have hereditary haemorrhagic telangiectasia (HHT), a condition that may be associated with pulmonary hypertension.

The current authors tested whether pulmonary AVM embolisation increases pulmonary artery pressure (Ppa) in patients without baseline severe pulmonary hypertension.Ppawas measured at the time of pulmonary AVM embolisation in 143 individuals, 131 (92%) of whom had underlying HHT. Angiography/embolisation was not performed in four individuals with severe pulmonary hypertension, whose systemic arterial oxygen saturation exceeded levels usually associated with dyspnoea in pulmonary AVM patients.

In 143 patients undergoing pulmonary AVM embolisation,Ppawas significantly correlated with age, with the most significant increase occurring in the upper quartile (aged >58 yrs). In 43 patients with repeated measurements, there was no significant increase inPpaas a result of embolisation. In half, embolisation led to a fall inPpa. The maximum rise in meanPpawas 8 mmHg: balloon test occlusion was performed in one of these individuals, and did not predict the subsequent rise inPpafollowing definitive embolisation of the pulmonary AVMs.

In the present series of patients, which excluded those with severe pulmonary hypertension, pulmonary artery pressure was not increased significantly by pulmonary arteriovenous malformation embolisation.
Keratinocyte growth factor protects against Clara cell injury induced by naphthalene
Authors: Yildirim A. Ö. , Veith M. , Rausch T. , Müller B. , Kilb P. , Van Winkle L. S. , Fehrenbach H.
Published: April 2008

Airway epithelial cells are exposed to environmental toxicants that result in airway injury. Naphthalene (NA) causes site-selective damage to Clara cells in mouse distal airways. N-terminally truncated recombinant human keratinocyte growth factor (ΔN23-KGF) protects against acute lung injury. The present study investigated whether or not ΔN23-KGF protects against NA-induced acute Clara cell damage by measuring airway responses specifically and in order to identify underlying molecular mechanisms.

Mice were treated with ΔN23-KGF or PBS 33 h prior to injection of 200 mg·kg body weight−1NA. Lung function was analysed by head-out body plethysmography. Distal airways isolated by microdissection were assessed for cell permeability using ethidium homodimer-1. Immunohistochemistry of Clara cell-specific protein in conjunction with a physical dissector was used to quantify Clara cell numbers. RNA was isolated from frozen airways in order to analyse gene expression using quantitative RT-PCR.

ΔN23-KGF prevented NA-induced airflow limitation and Clara cell permeability, and resulted in twice as many Clara cells compared with PBS pre-treatment. ΔN23-KGF-pre-treated mice exhibited increased expression of proliferating cell nuclear antigen mRNA. Cytochrome P450isoform 2F2, which converts NA into its toxic metabolite, was reduced by ∼50%.

The present results demonstrate that pre-treatment with N-terminally truncated recombinant human keratinocyte growth factor protects against naphthalene-induced injury. This suggests that N-terminally truncated recombinant human keratinocyte growth factor exerts its beneficial effect through a decrease in the expression of cytochrome P450isoform 2F2.
Appropriateness of antibiotic treatment in intravenous drug users, a retrospective analysis
Authors: Mertz Dominik , Viktorin Nina , Wolbers Marcel , Laifer Gerd , Leimenstoll Bernd , Fluckiger Ursula , Battegay Manuel
Published: April 2008

Background

Infectious disease is often the reason for intravenous drug users being seen in a clinical setting. The objective of this study was to evaluate the appropriateness of treatment and outcomes for this patient population in a hospital setting.

Methods

Retrospective study of all intravenous drug users hospitalized for treatment of infectious diseases and seen by infectious diseases specialists 1/2001–12/2006 at a university hospital. Treatment was administered according to guidelines when possible or to alternative treatment program in case of patients for whom adherence to standard protocols was not possible. Outcomes were defined with respect to appropriateness of treatment, hospital readmission, relapse and mortality rates. For statistical analysis adjustment for multiple hospitalizations of individual patients was made by using a generalized estimating equation.

Results

The total number of hospitalizations for infectious diseases was 344 among 216 intravenous drug users. Skin and soft tissue infections (n = 129, 37.5% of hospitalizations), pneumonia (n = 75, 21.8%) and endocarditis (n = 54, 15.7%) were most prevalent. Multiple infections were present in 25%. Treatment was according to standard guidelines for 78.5%, according to an alternative recommended program for 11.3%, and not according to guidelines or by the infectious diseases specialist advice for 10.2% of hospitalizations. Psychiatric disorders had a significant negative impact on compliance (compliance problems in 19.8% of hospitalizations) in multiple logistic regression analysis (OR = 2.4, CI 1.1–5.1, p = 0.03). The overall readmission rate and relapse rate within 30 days was 13.7% and 3.8%, respectively. Both non-compliant patient behavior (OR = 3.7, CI 1.3–10.8, p = 0.02) and non-adherence to treatment guidelines (OR = 3.3, CI 1.1–9.7, p = 0.03) were associated with a significant increase in the relapse rate in univariate analysis. In 590 person-years of follow-up, 24.6% of the patients died: 6.4% died during hospitalization (1.2% infection-related) and 13.6% of patients died after discharge.

Conclusion

Appropriate antibiotic therapy according to standard guidelines in hospitalized intravenous drug users is generally practicable and successful. In a minority alternative treatments may be indicated, although associated with a higher risk of relapse.
Sex-specific incidence and temporal trends in solid tumours in young people from Northern England, 1968–2005
Authors: Magnanti Brooke L , Dorak M Tevfik , Parker Louise , Craft Alan W , James Peter W , McNally Richard JQ
Published: April 2008

Background

This study examined sex-specific patterns and temporal trends in the incidence of solid tumours in the Northern Region of England from 1968 to 2005. This updates earlier analyses from the region where sex was not considered in depth. Sex-specific analyses were carried out to determine whether sex differences might provide clues to aetiology.

Methods

Details of 3576 cases, aged 0–24 years, were obtained from a specialist population-based cancer registry. There were 1843 males (886 aged 0–14 years and 957 aged 15–24 years) and 1733 females (791 aged 0–14 years and 942 aged 15–24 years). Age-standardized incidence rates (per million population) were calculated. Linear regression was used to analyze temporal trends in incidence and annual percentage changes were estimated. Analyses were stratified by sex and by age-group.

Results

There were marked differences in incidence patterns and trends between males and females and also between age-groups. For males central nervous system (CNS) tumours formed the largest proportion of under-15 cases and germ cell tumours was the largest group in the 15–24's, whilst for females CNS tumours dominated in the under-15's and carcinomas in the older group. For 0–14 year olds there were male-specific increases in the incidence of rhabdomyosarcoma (2.4% per annum; 95% CI: 0.2%–4.5%) and non-melanotic skin cancer (9.6%; 95% CI: 0.0%–19.2%) and female-specific increases for sympathetic nervous system tumours (2.2%; 95% CI: 0.4%–3.9%), gonadal germ cell tumours (8.6%; 95% CI: 4.3%–12.9%) and non-gonadal germ cell tumours (5.4%; 95% CI: 2.8%–7.9%). For 15–24 year olds, there were male-specific increases in gonadal germ cell tumours (1.9%; 95% CI: 0.3%–3.4%), non-gonadal germ cell tumours (4.4%; 95% CI: 1.1%–7.7%) and non-melanotic skin cancer (4.7%; 95% CI: 0.5%–8.9%) and female-specific increases for osteosarcoma (3.5%; 95% CI: 0.5%–6.5%), thyroid cancer (2.8%; 95% CI: 0.1%–5.6%) and melanoma (4.6%; 95% CI: 2.2%–7.1%).

Conclusion

This study has highlighted notable differences between the sexes in incidence patterns and trends for solid tumours. Some of these sex-specific differences could have been obscured if males and females had been analysed together. Furthermore, they suggest aetiological differences or differential susceptibility to environmental factors between males and females.
Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice
Authors: Williams Jason H , Schray Rebecca C , Sirsi Shashank R , Lutz Gordon J
Published: April 2008

Background

Exon skipping oligonucleotides (ESOs) of 2'O-Methyl (2'OMe) and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from themdxmouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD). However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) are regarded as effective agents for enhanced delivery of nucleic acids in various applications.

Results

We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA) muscles ofmdxmice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG) or adsorbtion of colloidal gold (CG), respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal levels were found at 6 weeks after 10 twice-weekly injections of the NG-PEI2K-PEG550 copolymer complexed with 5 μg of ESO per injection. This injection and dosing regimen showed over 1000 dystrophin-positive fibers. H&E staining of all treated muscle groups revealed no overt signs of cytotoxicity.

Conclusion

We conclude that PEGylated PEI2K copolymers are efficient carriers for local delivery of 2'OMe ESOs and warrant further development as potential therapeutics for treatment of DMD.
Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans
Authors: Hu Guanggan , Liu Iris , Sham Anita , Stajich Jason E , Dietrich Fred S , Kronstad James W
Published: April 2008

Background

Genome variability can have a profound influence on the virulence of pathogenic microbes. The availability of genome sequences for two strains of the AIDS-associated fungal pathogen Cryptococcus neoformans presented an opportunity to use comparative genome hybridization (CGH) to examine genome variability between strains of different mating type, molecular subtype, and ploidy.

Results

Initially, CGH was used to compare the approximately 100 kilobase MATa and MATα mating-type regions in serotype A and D strains to establish the relationship between the Log2 ratios of hybridization signals and sequence identity. Subsequently, we compared the genomes of the environmental isolate NIH433 (MATa) and the clinical isolate NIH12 (MATα) with a tiling array of the genome of the laboratory strain JEC21 derived from these strains. In this case, CGH identified putative recombination sites and the origins of specific segments of the JEC21 genome. Similarly, CGH analysis revealed marked variability in the genomes of strains representing the VNI, VNII, and VNB molecular subtypes of the A serotype, including disomy for chromosome 13 in two strains. Additionally, CGH identified differences in chromosome content between three strains with the hybrid AD serotype and revealed that chromosome 1 from the serotype A genome is preferentially retained in all three strains.

Conclusion

The genomes of serotypes A, D, and AD strains exhibit extensive variation that spans the range from small differences (such as regions of divergence, deletion, or amplification) to the unexpected disomy for chromosome 13 in haploid strains and preferential retention of specific chromosomes in naturally occurring diploids.
A pathway sensor for genome-wide screens of intracellular proteolytic cleavage
Authors: Ketteler Robin , Sun Zairen , Kovacs Karl F , He Wei-Wu , Seed Brian
Published: April 2008

Protein cleavage is a central event in many regulated biological processes. We describe a system for detecting intracellular proteolysis based on non-conventional secretion of Gaussia luciferase (GLUC). GLUC exits the cell without benefit of a secretory leader peptide, but can be anchored in the cell by fusion to β-actin. By including protease cleavage sites between GLUC and β-actin, proteolytic cleavage can be detected. Using this assay, we have identified regulators of autophagy, apoptosis and β-actin cleavage.
Dynamic regulation of the expression of neurotrophin receptors by Runx3
Authors: Nakamura Souichiro , Senzaki Kouji , Yoshikawa Masaaki , Nishimura Mika , Inoue Ken-ichi , Ito Yoshiaki , Ozaki Shigeru , Shiga Takashi
Published: April 2008

Sensory neurons in the dorsal root ganglion (DRG) specifically project axons to central and peripheral targets according to their sensory modality. However, the molecular mechanisms that govern sensory neuron differentiation and the axonal projections remain unclear. The Runt-related transcription factors, Runx1 and Runx3, are expressed in DRG neuronal subpopulations,suggesting that they might regulate the cell specification and the trajectories of specific axons. Here, we show that parvalbumin-positive DRG neurons fail to differentiate from the onset in Runx3-/-mice. By contrast, TrkC-positive DRG neurons differentiate normally at embryonic day (E) 11.5, but disappear by E13.5 in Runx3-/-mice. Subsequently, TrkC-positive DRG neurons reappear but in smaller numbers than in the wild type. In Runx3-/- mice, central axons of the TrkC-positive DRG neurons project to the dorsal spinal cord but not to the ventral and intermediate spinal cord, whereas the peripheral axons project to skin but not to muscle. These results suggest that Runx3 controls the acquisition of distinct proprioceptive DRG neuron identities, and that TrkC-positive DRG neurons consist of two subpopulations: Runx3-dependent early-appearing proprioceptive neurons that project to the ventral and intermediate spinal cord and muscle; and Runx3-independent late-appearing cutaneous neurons that project to the dorsal spinal cord and skin. Moreover,we show that the number of TrkA-positive DRG neurons is reduced in Runx3-/- mice, as compared with the wild type. These results suggest that Runx3 positively regulates the expression of TrkC and TrkA in DRG neurons.
Cell polarity and cancer – cell and tissue polarity as a non-canonical tumor suppressor
Authors: Lee Minhui , Vasioukhin Valeri
Published: April 2008

Correct establishment and maintenance of cell polarity is required for the development and homeostasis of all metazoans. Cell-polarity mechanisms are responsible not only for the diversification of cell shapes but also for regulation of the asymmetric cell divisions of stem cells that are crucial for their correct self-renewal and differentiation. Disruption of cell polarity is a hallmark of cancer. Furthermore, recent evidence indicates that loss of cell polarity is intimately involved in cancer: several crucial cell-polarity proteins are known proto-oncogenes or tumor suppressors, basic mechanisms of cell polarity are often targeted by oncogenic signaling pathways, and deregulation of asymmetric cell divisions of stem or progenitor cells may be responsible for abnormal self-renewal and differentiation of cancer stem cells. Data from in vivo and three-dimensional (3D) cell-culture models demonstrate that tissue organization attenuates the phenotypic outcome of oncogenic signaling. We suggest that polarized 3D tissue organization uses cell-cell and cell-substratum adhesion structures to reinforce and maintain the cell polarity of pre-cancerous cells. In this model, polarized 3D tissue organization functions as a non-canonical tumor suppressor that prevents the manifestation of neoplastic features in mutant cells and, ultimately, suppresses tumor development and progression.
SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2
Authors: Shin Narae , Ahn Namhui , Chang-Ileto Belle , Park Joohyun , Takei Kohji , Ahn Sang-Gun , Kim Soo-A , Di Paolo Gilbert , Chang Sunghoe
Published: April 2008

Dynamic membrane remodeling during intracellular trafficking is controlled by the intricate interplay between lipids and proteins. BAR domains are modules that participate in endocytic processes by binding and deforming the lipid bilayer. Sorting nexin 9 (SNX9), which functions in clathrin-mediated endocytosis, contains a BAR domain, however, the properties of this domain are not well understood. Here we show that SNX9 shares many properties with other BAR domain-containing proteins, such as amphiphysin and endophilin. SNX9 is able to deform the plasma membrane, as well as liposomes, into narrow tubules and recruit N-WASP and dynamin 2 to these tubules via its SH3 domain. SNX9-induced tubulation is antagonized by N-WASP and dynamin 2 while it is enhanced by perturbation of actin dynamics. However, SNX9 also has several unique properties. The tubulating activity requires the BAR and PX domains, as well as the low-complexity (LC) domain, which binds the Arp2/3 complex. SNX9 also binds to PtdIns(4)P-5-kinases via its PX domain and its tubulating activity is regulated by phosphoinositides. In addition, the kinase activity of PtdIns(4)P-5-kinases is stimulated by interaction with SNX9, suggesting a positive feedback interaction between SNX9 and PtdIns(4)P-5-kinases. These results suggest that SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes.
Influence of irofulven, a transcription-coupled repair-specific antitumor agent, on RNA polymerase activity, stability and dynamics in living mammalian cells
Authors: Escargueil Alexandre E. , Poindessous Virginie , Soares Daniele Grazziotin , Sarasin Alain , Cook Peter R. , Larsen Annette K.
Published: April 2008

Transcription-coupled repair (TCR) plays a key role in the repair of DNA lesions induced by bulky adducts and is initiated when the elongating RNA polymerase II (Pol II) stalls at DNA lesions. This is accompanied by alterations in Pol II activity and stability. We have previously shown that the monofunctional adducts formed by irofulven (6-hydroxymethylacylfulvene) are exclusively recognized by TCR, without involvement of global genome repair (GGR), making irofulven a unique tool to characterize TCR-associated processes in vivo. Here, we characterize the influence of irofulven on Pol II activity, stability and mobility in living mammalian cells. Our results demonstrate that irofulven induces specific inhibition of nucleoplasmic RNA synthesis, an important decrease of Pol II mobility, coupled to the accumulation of initiating polymerase and a time-dependent loss of the engaged enzyme, associated with its polyubiquitylation. Both proteasome-mediated degradation of the stalled polymerase and new protein synthesis are necessary to allow Pol II recycling into preinitiating complexes. Together, our findings provide novel insights into the subsequent fate of the stalled RNA polymerase II and demonstrate the essential role of the recycling process for transcriptional reinitiation and viability of mammalian cells.
CCAAT/enhancer binding protein β deficiency provides cerebral protection following excitotoxic injury
Authors: Cortes-Canteli Marta , Luna-Medina Rosario , Sanz-SanCristobal Marina , Alvarez-Barrientos Alberto , Santos Angel , Perez-Castillo Ana
Published: April 2008

The CCAAT/enhancer-binding protein β (C/EBPβ, also known as CEBPB) was first identified as a regulator of differentiation and inflammatory processes in adipose tissue and liver. Although C/EBPβ was initially implicated in synaptic plasticity, its function in the brain remains largely unknown. We have previously shown that C/EBPβ regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have demonstrated that the expression of C/EBPβ is notably increased in the hippocampus in a murine model of excitotoxicity. Mice lacking C/EBPβ showed a reduced inflammatory response after kainic acid injection, and exhibited a dramatic reduction in pyramidal cell loss in the CA1 and CA3 subfields of the hippocampus. These data reveal an essential function for C/EBPβ in the pathways leading to excitotoxicity-mediated damage and suggest that inhibitors of this transcription factor should be evaluated as possible neuroprotective therapeutic agents.
Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors
Authors: Mishra Sanjay K. , Jha Anupma , Steinhauser Amie L. , Kokoza Vladimir A. , Washabaugh Charles H. , Raikhel Alexander S. , Foster Woodbridge A. , Traub Linton M.
Published: April 2008

In the anautogenous disease vector mosquitoes Anopheles gambiae and Aedes aegypti, egg development is nutritionally controlled. A blood meal permits further maturation of developmentally repressed previtellogenic egg chambers. This entails massive storage of extraovarian yolk precursors by the oocyte, which occurs through a burst of clathrin-mediated endocytosis. Yolk precursors are concentrated at clathrin-coated structures on the oolemma by two endocytic receptors, the vitellogenin and lipophorin receptors. Both these mosquito receptors are members of the low-density-lipoprotein-receptor superfamily that contain FxNPxY-type internalization signals. In mammals, this tyrosine-based signal is not decoded by the endocytic AP-2 adaptor complex directly. Instead, two functionally redundant phosphotyrosine-binding domain adaptors, Disabled 2 and the autosomal recessive hypercholesterolemia protein (ARH) manage the internalization of the FxNPxY sorting signal. Here, we report that a mosquito ARH-like protein, which we designate trephin, possess similar functional properties to the orthologous vertebrate proteins despite engaging AP-2 in an atypical manner, and that mRNA expression in the egg chamber is strongly upregulated shortly following a blood meal. Temporally regulated trephin transcription and translation suggests a mechanism for controlling yolk uptake when vitellogenin and lipophorin receptors are expressed and clathrin coats operate in previtellogenic ovaries.
Three-dimensional finite element method simulation of sheet metal single-point incremental forming and the deformation pattern analysis
Authors: Ma L-W , Mo J-H
Published: April 2008

Further research of the sheet metal single-point incremental forming (SPIF), which is a flexible sheet metal numerical forming method without dedicated dies, has used finite element method (FEM) simulation to analyse the forming principle and the effect of process parameters on the forming. In SPIF, the located region of the blank in contact with the forming tool is formed incrementally along the trajectory. There is no symmetric load and geometry condition, so the FEM model could not be simplified to a symmetrical model and the efficiency of simulation is bad. In this paper, brick elements are used to establish the whole three-dimensional FEM model and a simplified three-dimensional FEM model of a truncated cone and truncated pyramid. Comparison of the simulation results from the two models indicates that both models fit the simulation of SPIF but the simplified model is more efficient. Therefore, based on the simplified FEM model of a truncated pyramid, the SPIF process with different parameters was simulated to study the incremental forming principle. It was found that the deformed blank could be divided into three regions with different deformation patterns and the main character of the deformation could be conceded as a combination of bending and stretching.
An expression of stress concentration factor for a circular hole eccentrically located in a tensile finite-width strip of orthotropic material
Authors: Wang Q Z. , Song X L.
Published: April 2008

An explicit expression of stress concentration factor (SCF) for a circular hole eccentrically located in a finite-width strip of orthotropic material subjected to remote tension is derived using an approximate and analytical method. The eccentricity of the hole and the ratio of the diameter to strip width are two governing geometric parameters, and their effect to the SCF is shown clearly in the expression. The formulation for the expression is consisted of two steps, first, the derivation is based on section method using balance of force and moment, respectively, second, improvement is done by empirical modification of the related coefficients based on asymptotic matching of good results obtained for some special cases. The accuracy of the final SCF expressions is adequate except the extreme case where the eccentricity of the circular hole is very large, i.e. when the hole is located very near to one side of the strip. On the other hand, when the eccentricity is taken as zero, i.e. for the simplified case of a central circular hole in a finite-width strip, the corresponding SCF expression has good accuracy. The present work is an extension of previous work for central circular hole of orthotropic material and an eccentric circular hole for isotropic material.
Economic Forecasting
Authors: Elliott Graham , Timmermann Allan
Published: April 2008

Forecasts guide decisions in all areas of economics and finance and their value can only be understood in relation to, and in the context of, such decisions. We discuss the central role of the loss function in helping determine the forecaster's objectives. Decision theory provides a framework for both the construction and evaluation of forecasts. This framework allows an understanding of the challenges that arise from the explosion in the sheer volume of predictor variables under consideration and the forecaster's ability to entertain an endless array of forecasting models and time-varying specifications, none of which may coincide with the “true” model. We show this along with reviewing methods for comparing the forecasting performance of pairs of models or evaluating the ability of the best of many models to beat a benchmark specification.
A Case of Severe Caries and Demineralisation in a Patient Wearing an Essix-Type Retainer
Authors: Birdsall Jo , Robinson Stephen
Published: April 2008

This case report presents a patient who developed significant caries and demineralisation due to consumption of large quantities of cariogenic drinks while he was wearing an Essix retainer. The risks to dental health during orthodontic retention and the responsibilities of general dental practitioners, orthodontists and patients are highlighted.
Denture Cleansers, Soft Lining Materials and Water Temperature: What is the Effect?
Authors: Handa Rajesh K , Jagger Daryll C , Vowles Richard W
Published: April 2008

Aim

To investigate the effect of water temperature, in association with four denture cleansers, on the colour and surface roughness of five soft lining materials.

Method

Two silicone soft lining materials (Molloplast B and Sofreliner) represented the heat-cured, laboratory-based and chairside materials that are available. The wide range of chairside, acrylic resin-based, temporary soft lining materials was represented by Coe-Soft, Viscogel and Eversoft. An alkaline hypochlorite (Dentural) and three effervescent peroxide solutions with a range of active pH values (Steradent Active Plus, pH 6; Steradent Extra Strength, pH 3; Superdrug Fresh, pH 11) were selected as the cleansers. The denture cleansers were used at two temperatures: 55 °C (manufacturers’ recommended temperature) and 80 °C. The colour of the specimens was evaluated using a colorimeter and the surface roughness was assessed using a three-dimensional, non-contact surface profilometer. This study reported on the effect of using both the higher temperatures and the recommended temperature on the colour and roughness of permanent and temporary soft lining materials.

Results and Conclusion

The results of the study showed that the temperature of the water used with denture cleansers might have a detrimental effect on the colour and surface roughness of some permanent and temporary soft lining materials.
Training less than full-time in surgery
Authors: Walls Janet
Published: April 2008

To quote the chapter on 'Women in Medicine' in the chief medical officer's annual report, 'Today the problem is not access to medical school but rather how we ensure that the female medical workforce is able to fulfil its potential once in employment.' I would go further than this and extend the premise to all medical graduates entering a career in surgery. One of the main obstacles to career progression in surgery is the perceived poor quality of life while training. More latterly and more worryingly, this has extended to the belief that life as a consultant surgeon in the future will afford horizons no further than the theatre walls within which we work. One of the possible ways to try and improve work–life balance is to extend the period of time taken for training, such that surgical competency is achieved at an individual rate.
The Baha'i Faith and the Perennial Mystical Quest: A Western Perspective
Authors: Savi Julio
Published: April 2008

The author analyses a definition of mysticism formulated by William Ralph Inge and western ideas on mystical experience. Then he proceeds to discuss mysticism as an intrinsic aspect of the Baha'i Faith and mystical experience as expounded in the Baha'i writings. The latter pay greater
attention to the practical and logical aspects of mysticism than to the visionary and illogical ones. The author examines some of the reasons for Baha'i and non-Baha'i criticism of mysticism and suggests a Baha'i definition of mysticism. He then attempts to describe the Baha'i mystical path,
as expounded by the Universal House of Justice.
Open the social sciences: To whom and for what?, by Michael Burawoy
Authors: Pinto Jos Madureira
Published: April 2008

This text tries to demonstrate that Portuguese sociology has been built on a set of virtuous relations between four poles of sociological activity: the theoretical problematisation pole, the observational research pole, the reflexivity pole and the professionalisation pole. It is suggested
that this specific dynamic was favoured by a series of political-institutional and organisational conditions (the dominance of a critical/applied rationalism in university training, the active role of the Portuguese Sociological Association in the promotion of a creative interaction between
academics and field professionals, the political engagement of Portuguese sociologists, the relatively successful opening-up of the labour market to professionally trained sociologists, etc.) The text is, of course, punctuated with comments largely concordant, but sometimes critical on Michael
Burawoy's theses about the evolution and specificity of Portuguese sociology and the need to re-invent public sociology and reformulate the scientific agenda of the discipline.
Review
Authors: Castillo Francisco Javier Luque
Published: April 2008

Who governs southern Europe? Regime change and ministerial recruitment, 18502000, Almeida, P.T. de, Pinto, A.C. and Bermeo, N. (2003) London and Portland, OR: Frank Cass, 242 pp., ISBN 0714682772 (pbk), 75
Neosentience a new branch of scientific and poetic inquiry related to artificial intelligence
Authors: Seaman Bill , Rossler Otto
Published: April 2008

Neosentience, a potentially new branch of scientific inquiry related to artificial intelligence, was first suggested in a paper by Bill Seaman as part of a new embodied robotic paradigm, arising out of ongoing theoretical research with Otto E. Rossler. Seaman, artist-researcher, and Rossler, theoretical biologist and physicist, have been examining the potential of generating an intelligent, embodied, multimodal sensing and computational robotic system. Although related to artificial intelligence the goal of this system is the creation of an entity exhibiting a new form of sentience. Its unique qualities will be discussed. Sentience is not yet used in the formal languages of either cognitive science or artificial intelligence. Two related approaches are (1) the generation of artificial minds via parallel processing, in a robotic system; (2) an alternative approach is the generation of an electrochemical computer as a robotic system. Biomimetics, along with state-of-the-art computer visualization is employed. The electrochemical paradigm has a complexity that exceeds standard computational means. The scientific and the poetic elements of the project are motivated by human sentience. The sentient entity is initially modelled on our functional definition of human sentience. The system involves synthetic drives as a new element. We seek to articulate the differences to living brains. This transdisciplinary approach necessitates different forms of inquiry to inform this project such as cognitive science including psychology, education/learning, neuroscience, linguistics, philosophy, anthropology, biology and the arts. We believe that this area of research to be of importance.
Integrative art education in a metaverse: ground
Authors: Ayiter Elif
Published: April 2008

Virtual learning environments (VLEs) present us with unprecedented opportunities in bringing together students and educators from widely disparate geographical locations, as well as diverse cultures and backgrounds to participate in a learning experience that should take into cognizance the affordances of these novel arenas in the design of both content and the environment(s) in which this content is to be implemented/enacted. While VLEs do seem to address the requirements of well-structured learning endeavours, the boundaries of which are clearly defined, they are challenged where complex learning material in which boundaries are less easily defined, as is the case in art/creativity education, are concerned. Given that the learning content of the creative fields is open ended by its very nature and as such does not seem to readily lend itself to an implementation within the structure of present-day, two-dimensional virtual learning environments, can such an environment/methodology be developed in the open-ended three-dimensional structure of a metaverse, based upon the critical examination of a real-life, historic precedent?
Is premature induced labour justified in case of fetal urinary tract dilatation?
Authors: Merksz Miklós , Kiss András , Réti Gyula , Szabó László
Published: April 2008

There is a decreasing trend in the number of intrauterine interventions performed due to urinary tract dilatations of the foetus diagnosed ultrasonographically. This is due to the low efficacy of the interventions, the high rate of complications and a better knowledge of the foetal physiology. However, the demand for early corrective surgery is still present. In Hungary pre-term caesarean section is performed in many institutions in order to enable the operation of the neonate, despite the fact that the benefits of this intervention have not been established. Aim: In order to test the correctness of this practice, the authors conducted a retrospective analysis of the patients of two large case-volume paediatric institutions. Patients: In a period of 5 years, 329 neonates were followed due to intrauterine diagnosis of urinary tract dilatations (197 at the Department of Urology, Heim Pál Children’s Hospital in Budapest, whereas in Miskolc 132), including 13 cases where the urological anomaly was the indication for pre-term induction of labour. Results: Of the 13 neonates who had been delivered prematurely, none were operated before the postconceptional age of 40 weeks, and 3 subsequently required no surgical intervention. Two neonates developed life-threatening conditions that presumably could have been avoided without the premature caesarean section. Conclusions: The authors conclude that there are several arguments against pre-term delivery: 1. Prenatal diagnostics does not always yield as accurate information as the diagnostic procedures performed in infancy; 2. Intrauterine urinary tract dilatation often resolve spontaneously, superseding the need for both pre- and post-natal surgical interventions. 3. Scientific observations have confirmed that there is no difference between the efficacy of postnatal and pre-term interventions. Based on the above-mentioned, authors emphasize that this outdated practice can no longer be accepted, and call for good cooperation between the obstetrician, the paediatric urologist and nephrologist, to coordinate the management of the case.