bluuebunny/crossref_metadata_2025 huggingface dataset:
Peak Cardiac Power Output, Measured Noninvasively, Is a Powerful Predictor of Outcome in Chronic Heart Failure
Authors: Lang Chim C. , Karlin Paula , Haythe Jennifer , Lim Tiong K. , Mancini Donna M.
Published: January 2009

Background—

The cardiac output (CO) response to exercise and other invasively derived hemodynamic variables has been variably described to provide better prognostication than peak V
o
2
in patients with chronic heart failure. Using noninvasive measurements of CO during exercise, we compared the prognostic value of peak CO and cardiac power to peak V
o
2
in chronic heart failure patients.

Method and Results—

One hundred seventy-one consecutive patients with chronic heart failure underwent symptom limited bicycle exercise with noninvasive estimation of CO using an inert gas rebreathing method. An accurate measure of peak CO was obtained in 148 patients (85% of patients; mean age, 53�14 years; 80% male; left ventricular ejection fraction, 24�12%; ischemic etiology, 34%). Peak cardiac power was derived from the product of the peak mean arterial blood pressure and CO divided by 451. End points consisted of death, urgent heart transplant, or left ventricular assist device implantation. Duration of follow-up averaged 337�252 days (median, 295 days). Univariate and multivariate analysis were performed. The variables analyzed included peak V
o
2
, peak CO, peak cardiac power, V
e
/V
co
2
slope, and V
o
2
at anaerobic threshold. Event-free survival for the entire cohort was 83% with 5 deaths, 4 left ventricular assist device implants, and 16 urgent transplants. Peak V
o
2
was 12.9�4.5 mL/kg per min, and peak cardiac power was 1.7�0.9 W. Peak V
o
2
, peak CO, peak cardiac power, V
e
/V
co
2
slope, and V
o
2
at anaerobic threshold were predictive of outcome on univariate analysis. On multivariate analysis, peak cardiac power and peak CO were predictive of outcome with peak cardiac power being the most powerful independent predictor of outcome (
P
=0.01).

Conclusions—

Peak cardiac power, measured noninvasively, is an independent predictor of outcome that can enhance the prognostic power of peak V
o
2
in the evaluation of patients with heart failure.
Comparative Study of Vasodilators in an Animal Model of Chronic Volume Overload Caused by Severe Aortic Regurgitation
Authors: Plante Eric , Lachance Dominic , Beaudoin Jonathan , Champetier Serge , Roussel Élise , Arsenault Marie , Couet Jacques
Published: January 2009

Background—

Aortic regurgitation (AR) is a disease of chronic left ventricular (LV) volume overload. Over time, AR will lead to LV dilatation, hypertrophy, and loss of function. There is currently no medical treatment proven effective to slow the evolution of this cardiomyopathy. Vasodilators were once thought to have protective effects, but recent publications have cast some doubts about their effectiveness. We hypothesized that drugs targeting the renin-angiotensin system should be more effective than those having no direct effect on the renin-angiotensin system.

Methods and Results—

We designed a protocol comparing the effects of 3 vasodilators in a rat AR model (n=9 to 11 animals per group). The effects of a 6-month treatment of (1) nifedipine, (2) captopril, or (3) losartan were compared in male AR rats. Sham-operated and untreated AR animals were used as controls. Nifedipine-treated animals displayed hemodynamics, LV dilatation, hypertrophy, and loss of function similar to those of the untreated group. Both captopril and losartan were effective in improving hemodynamics, slow LV dilatation, hypertrophy, and dysfunction. Gene expression analysis confirmed the lack of effects of the nifedipine treatment at the molecular level.

Conclusions—

Using an animal model of severe AR, we found that vasodilators targeting the renin-angiotensin system were effective to slow the development of LV remodeling and to preserve LV function. As recently shown in the most recent human clinical trial, nifedipine was totally ineffective. Targeting the renin-angiotensin system seems a promising avenue in the treatment of this disease, and clinical trials should be carefully designed to re-evaluate the effectiveness of angiotensin I–converting enzyme inhibitors or angiotensin II receptor blockers in AR.
Association of Multiple Anthropometrics of Overweight and Obesity With Incident Heart Failure
Authors: Loehr Laura R. , Rosamond Wayne D. , Poole Charles , Marie McNeill Ann , Chang Patricia P. , Folsom Aaron R. , Chambless Lloyd E. , Heiss Gerardo
Published: January 2009

Background—

The association of central adiposity with incident heart failure (HF) has yet to be studied in a large population-based study.

Methods and Results—

The Atherosclerosis Risk in Communities study is an ongoing biracial population-based cohort of those aged 45 to 64 years from 4 US communities with 16 years’ median follow-up for incident, hospitalized, or fatal HF. Waist-hip ratio, waist circumference, and body mass index (BMI) were measured at baseline (1987–1989). After exclusions, the sample size was 14 641. BMI was categorized as <25, 25 to 29.9, and ≥30 kg/m
2
. Waist circumference and waist-hip ratio were divided into gender-specific tertiles. A first occurrence of
International Classification of Diseases, 9th Revision, Clinical Modification
, codes of HF, either hospital discharge (428.0 to 428.9; n=1451) or on a death certificate (428.0 to 428.9 or I50.0 to I50.9; n=77) was considered an HF event. Cox models were adjusted for alcohol use, smoking, age, center, and educational level. The adjusted hazard ratios for the highest category (obese) compared with the lowest were well above 1.0 for all 3 anthropometric measures (hazard ratio for 3rd versus 1st tertile of waist-hip ratio: 2.27 [1.71, 3.02] for white women; 3.24 [2.25, 4.65] for black women; 2.46 [1.95, 3.09] for white men; and 2.63 [1.90, 3.65] for black men). Hazard ratios for overweight were lower in magnitude, suggesting a graded response between body size and HF.

Conclusions—

Obesity and overweight, as measured by 3 different anthropometrics, were associated with incident HF in the Atherosclerosis Risk in Communities cohort. The current study does not support the superiority of waist-hip ratio and waist circumference over BMI for the prediction of incident HF.
Svalbard's Maritime Zones: The End of Legal Uncertainty?
Authors: Pedersen Torbjørn , Henriksen Tore
Published: January 2009

This paper argues that Norway, by fixing the extension of the continental shelf around the Svalbard archipelago according to criteria set by the Law of the Sea Convention, may see an end to some of the legal controversies regarding the maritime zones around Svalbard. The process of determining the outer limits of the continental shelf area adjacent to Svalbard is adduced as supporting the view that Norway is entitled to establish maritime zones around the archipelago, including an exclusive economic zone. It does not settle whether the provisions of the Svalbard Treaty apply to such zones, but is adduced as supporting the view that Norway may exercise coastal state jurisdiction in these areas.
Balancing a Child's Best Interests and a Child's Views
Authors: Archard David , Skivenes Marit
Published: January 2009

We consider the problem of reconciling the two commitments to hear a child and to promote a child's best interests by identifying the principal issues at stake and illustrating them by reference to legal decision-making in the domains of health in the United Kingdom and custody and child protection in Norway. We agree that a child's views are not authoritative but dispute Harry Brighouse's claim that they are only of consultative value, affirming the fundamental right of a child capable of expressing a view of doing so and of thereby participating in the procedures where decisions affecting his or her interests are made. In conclusion we offer a checklist of questions that need to be asked about the way in which jurisdictions combine their explicit commitments to the two principles of best interests and hearing the child's views.
The Other and the Beyond
Authors: Murray Donal
Published: January 2009

Only in recognizing others do I recognize myself and my identity. The knowledge involved is not of the kind revealed by chemical analysis. It involves being present to and indeed loving the other person as `another I.' This points me beyond my own goals and perspectives. It shows me that there are other, equally valid, perspectives that I can never fully know. Indeed I can never fully know myself. Knowing and loving another person opens up a longing for fulfilment and for immortality. `To love a being is to say you … will never die.' It also opens up the longing for a justice which no human effort can achieve. The Christian Gospel offers hope for all humanity, a hope which will fulfil all the deepest longings of people of every time and culture. It offers the fulfilment of Marcel's formulation of hope: `I hope in Thee for us.'
What is the Goal of Systematic Theology?
Authors: Ormerod Neil
Published: January 2009

Following on the recent publication by Robert Doran of What Is Systematic Theology? the article examines the goal of systematic theology through an examination of contrasting positions: is the goal the understanding of data (for example, the data of the Scriptures) or the understanding of truth (as mediated by the Scriptures)? It argues that current work by systematicians illustrates a confusion over these two positions and demonstrates this confusion by reference to the Trinitarian theology of David Coffey and Thomas Weinandy.
Theology as a Road to Sanctification?
Authors: Ryan Fáinche
Published: January 2009

This article utilizes the work of St Thomas Aquinas to consider the role theology plays in the sanctification of the human person. The theology in question is clearly defined as the theology included in sacred teaching (theologia quae ad sacram doctrinam pertinet), an activity identified by Thomas as `necessary for salvation.' Somewhat provocatively a certain parallelism is suggested between the `sacrament' of theology and the more formal sacraments of the Church, as all are involved in the sanctification of the People of God. The potential transformative nature of teaching is likened to the change that sacraments can effect. In both the sacraments of the Church and the theology which pertains to sacred teaching, faith is identified as foundational. The central thesis of the article is the claim that knowledge of God, the Holy One, which the activity of theology facilitates, can make the `knower' holy.
Analysis of errors in degree days for building energy analysis using Meteorological Office weather station data
Authors: Layberry RL
Published: January 2009

Heating degree days are widely used in building energy management for weather normalization of energy use. Degree days are normally calculated at Meteorological Office weather stations sited some distance from the building of interest and this can introduce errors between the degree days used in the calculations and the actual degree days at the building. This paper analyses the major sources of errors in the degree days derived from a newly available data set of Met. Office stations supplied by the British Atmospheric Data Survey (BADC) and compares these errors against those from other available data sets. The BADC data set consists of hourly temperatures for 242 weather stations in the UK from January 2001 until November 2007 and has been converted to monthly degree days for the analysis. The errors have been analysed in terms of measurement and recording errors, errors due to altitude and errors due to spatial separation between weather station and building. The largest error is due to spatial separation between building and weather station. It is therefore important to use data sets with high numbers of weather stations. The data set used in this analysis has been made available on the internet at http:// www.eci.ox.ac.uk/research/energy/degreedays.php and consists of daily, weekly and monthly degree days for over 200 UK weather stations at a range of building base temperatures for the years 1987—2006. Also included is the 20-year mean for the 55 stations with unbroken records for benchmarking purposes.

Practical application: The paper discusses how errors arise in degree day data when using Met. Office weather stations sited some distance from the building of interest. The paper discusses both the method and the extent of reductions in errors that are possible by using spatially rich weather station degree day data sets. The paper makes the data set used — the best for UK degree day monitoring of buildings — available through a website, daily, weekly and monthly, over a range of building base temperatures, back to 1986.
Performance evaluation of dual-flush WC cistern in a multifamily building in Brazil
Authors: Oliveira LH , Gonçalves OM , Uchida C.
Published: January 2009

The performance assessment as to water consumption in WC cisterns has contributed to the development of flushing system technologies, which allow smaller flushing volumes. The purpose of this work is to assess the performance of the the low water consumption requirement of WC cisterns with dual flushing system (6/3 L), when compared to 6 L flushing volume WC cisterns in multifamily buildings. The research methodology consisted of a case study in a multifamily residential building with submetering system, by monitoring the total water consumption and the two flushing systems using water meters installed in WC cisterns. By means of a mathematical model, a comparison of the design flowrate in the main branch was carried out considering the two types of WC cisterns. The results indicated that the water consumption in the 6 L WC cistern was 20% in relation to the total domestic consumption, whereas the water consumption observed in the dual-flush WC cistern (6/3 L) was 16%. The dual flushing system (6/3 L) presented about 18% consumption reduction impact as compared to the 6 L system. The design flowrate values in the main branch, obtained by the mathematical model, were 0.35 L/s for systems with 6 L WC cistern and 0.34 L/s with dual-flush WC cistern (6/3 L), that is, a reduction of ~3%.

Practical application: The knowledge of the performance in field of dual-flush WC cistern contributes to industry to improve this system and to users to aid their choice of technologies aimed at water conservation, and so assisting to the development of sustainable buildings.
Morphologic and Immunohistochemical Features of the Cynomolgus Macaque Cervix
Authors: Wood Charles E.
Published: January 2009

Female macaques serve as an important model for the study of reproductive diseases in women. Here we summarize characteristics of the macaque cervix, with a particular emphasis on the cynomolgus macaque. Key anatomic features include a stratified squamous exocervix, squamocolumnar junction and transformation zone, and glandular endocervix with prominent colliculi. Endocervical eversion occurs with onset of ovarian cycling and regresses to varying degrees based on age, hormonal status, and individual conformation. The cervical epithelium in macaques is highly responsive to estrogens, which induce marked squamous epithelial maturation and glandular hypertrophy. Progestogen effects include further induction of endocervical secretory activity and release of viscous mucus, which functions in both mucosal immunity and fertility regulation. On immunohistochemistry, the squamous cervix shows strong expression of estrogen receptor α, the proliferation marker Ki67/MIB1, and cytokeratin 14, whereas endocervical epithelium strongly expresses estrogen and progesterone receptors and cytokeratins 18 and 19. These patterns of expression are altered in cervical intraepithelial neoplasia, which is a common spontaneous lesion of the macaque cervix associated with specific types of oncogenic papillomaviruses. This report highlights important similarities with human cervix that should be useful for future studies of genital infection, neoplasia, and immunity in the macaque model.

Competing Interests: This article was sponsored by Covance Inc. and Schering-Plough. The author did not declare any other competing interests.
The Macaque Endometrium, with Special Reference to the Cynomolgus Monkey (Macaca fascicularis)
Authors: van Esch Eric , Cline J. Mark , Buse Eberhard , Weinbauer Gerhard F.
Published: January 2009

The macaque endometrium undergoes dramatic morphologic and functional changes during the menstrual cycle that are nearly identical to those of the human endometrium. The sequential events that take place in the endometrium are mainly driven by the ovarian steroids and their respective receptors. To be able to interpret the changes and effects induced by mammalian or synthetic hormones and other compounds that could have influence on the hormonal status of the animal, a thorough knowledge of the anatomy, physiology, and histology of the cyclic hormone-mediated processes within the endometrium is indispensable. In this paper we give an overview of uterine growth and development, anatomy, basic histology, aging, spontaneous pathology, and the techniques to study the endometrium in-life. In addtion, a comprehensive description of the receptor-mediated, hormone-driven morphological changes during the menstrual cycle in the cynomolgus monkey (Macaca fascicularis) is given. Where possible, differences between the macaque and human endometria are discussed.

Competing Interests: This article was sponsored by Covance Inc. and Schering-Plough. Gerhard F. Weinbauer and Eberhard Buse are employed by Covance Inc. Eric Van Esch is employed by Schering-Plough. No other competing interests were declared.
Girls make sense
Authors: Duits Linda , van Romondt Vis Pauline
Published: January 2009

Combining intertextual, audience and feminist perspectives, this article investigates how young girls make meaning from celebrities. Based on focus group interviews with Dutch girls aged 12—13, it argues that girls' talk about celebrities functions as an identity tool in the reflexive project of the self. Alternating three repertoires (identification, makeability and authenticity), the girls appropriated narratives of celebrities to themselves and others in their everyday lives. The article adds knowledge about the reception of celebrities in Dutch multicultural society, intervenes in feminist discussions about girls and their agency, and contributes empirically to the literature about audiences and celebrities, more specifically to the notions of reflexivity and identification.
Intramuscular Electrical Stimulation for Upper Limb Recovery in Chronic Hemiparesis: An Exploratory Randomized Clinical Trial
Authors: Chae John , Harley Mary Y. , Hisel Terri Z. , Corrigan Catherine M. , Demchak Jeffrey A. , Wong Yu-Tung , Fang Zi-Ping
Published: January 2009

Background. Surface electrical stimulation (ES) has been shown to improve the motor impairment of stroke survivors. However, surface ES can be painful and motor activation can be inconsistent from session to session. Percutaneous intramuscular ES may be an effective alternative. Objective. Evaluate the effectiveness of percutaneous intramuscular ES in facilitating the recovery of the hemiparetic upper limb of chronic stroke survivors. Methods. A total of 26 chronic stroke survivors were randomly assigned to percutaneous intramuscular ES for hand opening (n = 13) or percutaneous ES for sensory stimulation only (n = 13). The intramuscular ES group received cyclic, electromyography (EMG)-triggered or EMG-controlled ES depending on baseline motor status. All participants received 1 hour of stimulation per day for 6 weeks. After completion of ES, participants received 18 hours of task-specific functional training. The primary outcome measure was the Fugl-Meyer Motor Assessment. Secondary measures included the Arm Motor Ability Test and delay and termination of EMG activity. Outcomes were assessed in a blinded manner at baseline, at the end of ES, at the end of functional training, and at 1, 3, and 6 months follow-up. Results. Repeated measure analysis of variance did not yield any significant treatment, or time by treatment interaction effects for any of the outcome measures. Conclusion. Percutaneous intramuscular ES does not appear to be any more effective than sensory ES in enhancing the recovery of the hemiparetic upper limb among chronic stroke survivors. However, because of the exploratory nature of the study and its inherent limitations, conclusions must be drawn with caution.
Identification of novel Bach2 transcripts and protein isoforms through tagging analysis of retroviral integrations in B-cell lymphomas
Authors: Liu Jinghua , Sørensen Annette Balle , Wang Bruce , Wabl Matthias , Nielsen Anders Lade , Pedersen Finn Skou
Published: January 2009

Background

The Bach2 gene functions as a transcriptional repressor in B-cells, showing high expression level only before the plasma cell stage. Several lines of evidence indicate that Bach2 is a B-cell specific tumor suppressor. We here address patterns of insertional mutagenesis and expression of Bach2 is a murine retroviral model of B-cell lymphoma induction.

Results

We report that the Bach2 gene is a target of proviral integrations in B-cell lymphomas induced by murine leukemia virus. An alternative Bach2 promoter was identified within intron 2 and this promoter was activated in one of the tumors harboring proviral integration. The alternative promoter was active in both normal and tumor tissue and the tissue specificity of the two Bach2 promoters was similar. Three different alternatively used Bach2 terminal exons were identified to be located in intron 4. The inclusion of these exons resulted in the generation of Bach2 mRNA with open reading frames lacking the bZIP DNA binding domain present in the normal Bach2 protein, but retaining a partial BTB protein dimerization domain. Such Bach2 protein was excluded from the cell nucleus.

Conclusion

We have identified an alternative promoter and new protein isoforms of Bach2. Our data imply that activation of an alternative promoter by proviral integration serves as a possible mechanism of up-regulation of the Bach2 gene with a potential role in B-cell lymphomagenesis. The finding of novel Bach2 transcripts and protein isoforms will facilitate a better insight into the normal and pathophysiological regulation of the Bach2 gene.
Evidence for separate translocation pathways in determining cadmium accumulation in grain and aerial plant parts in rice
Authors: Kashiwagi Takayuki , Shindoh Kumiko , Hirotsu Naoki , Ishimaru Ken
Published: January 2009

Background

Cadmium (Cd) translocation and accumulation in the grain and aerial plant parts of rice (Oryza sativa L.) is an important aspect of food safety and phytoextraction in areas with contaminated soil. Because control of Cd translocation and accumulation is likely to be determined by the plants genetics, the Cd contents of grain and the aerial parts of rice may be manipulated to improve food safety and for phytoextraction ability. This study studied Cd translocation and accumulation and their genetic control in aerial parts of rice to provide a starting point for improving food safety and phytoextraction in Cd-contaminated soils.

Results

In the japonica rice cultivar "Nipponbare", Cd accumulated in leaves and culms until heading, and in culms and ears after heading. Two quantitative trait loci (QTLs) from indica cv. "Kasalath", qcd4-1 and qcd4-2, affect Cd concentrations in upper plant parts just before heading. Three near-isogenic lines (NILs) with qcd4-1 and qcd4-2 were selected from the "Nipponbare" background, and were analyzed for the effects of each QTL, and for interactions between the two QTLs. From the results compared between "Nipponbare" and each NIL, neither QTL influenced total Cd accumulation in aerial parts at 5 days after heading, but the interaction between two QTLs increased Cd accumulation. At 35 days after heading, qcd4-2 had increased Cd accumulation in the aerial plant parts and decreased translocation from leaves other than flag leaf, but interaction between the two QTLs increased translocation from leaves. NILqcd4-1,2 accumulated higher concentrations of Cd in brown rice than "Nipponbare".

Conclusion

Three types of Cd translocation and accumulation patterns demonstrated by NILs suggested that the accumulation of Cd in leaves and culms before heading, and translocation from them after heading are responsible for Cd accumulation in grain. Cd translocation from roots to culms and ears after heading may direct Cd to the aerial organs without influencing brown rice accumulation.
n3 and n6 polyunsaturated fatty acids differentially modulate prostaglandin E secretion but not markers of lipogenesis in adipocytes
Authors: Wortman Patrick , Miyazaki Yuko , Kalupahana Nishan S , Kim Suyeon , Hansen-Petrik Melissa , Saxton Arnold M , Claycombe Kate J , Voy Brynn H , Whelan Jay , Moustaid-Moussa Naima
Published: January 2009

A dramatic rise in the incidence of obesity in the U.S. has accelerated the search for interventions that may impact this epidemic. One recently recognized target for such intervention is adipose tissue, which secretes a variety of bioactive substances including prostaglandins. Prostaglandin E2 (PGE2) has been shown to decrease lipolysis in adipocytes, but limited studies have explored alternative mechanisms by which PGE2 might impact obesity, such as adipogenesis or lipogenesis. Studies conducted on Apc
Min/+ mice indicated that selective inhibition of the cyclooxygenase (COX)-2 enzyme led to significant reductions in fatty acid synthase (FAS) activity in adipose tissue suggesting lipogenic effects of PGE2. To further investigate whether these lipid mediators directly regulate lipogenesis, we used 3T3-L1 adipocytes to determine the impact of eicosapentaenoic acid (EPA) and celecoxib on PGE2 formation and FAS used as a lipogenic marker. Both arachidonic acid (AA) and EPA dose-dependently increased PGE secretion from adipocytes. AA was expectedly more potent and exhibiting at 150 uM dose a 5-fold increase in PGE2 secretion over EPA. Despite higher secretion of PGE by EPA and AA compared to control, neither PUFA significantly altered FAS activity. By contrast both AA and EPA significantly decreased FAS mRNA levels. Addition of celecoxib, a selective COX-2 inhibitor, significantly decreased PGE2 secretion (p < 0.05) versus control, and also significantly decreased FAS activity (p < 0.05). Unexpectedly, the combination of exogenous PGE2 and celecoxib further decreased the FAS activity compared to PGE2 alone or untreated controls. In conclusion, EPA-mediated inhibition of AA metabolism did not significantly alter FAS activity while both AA and EPA significantly decreased FAS mRNA expression. COX-2 inhibition significantly decreased PGE2 production resulting in a decrease in FAS activity and expression that was not reversed with the addition of exogenous PGE2, suggesting an additional mechanism that is independent of COX-2.
Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory
Authors: Ko Hyoung-Gon , Jang Deok-Jin , Son Junehee , Kwak Chuljung , Choi Jun-Hyeok , Ji Young-Hoon , Lee Yun-Sil , Son Hyeon , Kaang Bong-Kiun
Published: January 2009

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.
Recent advances of novel targeted therapy in non-small cell lung cancer
Authors: Katzel Jed A , Fanucchi Michael P , Li Zujun
Published: January 2009

Lung cancer is the leading cause of cancer deaths world-wide. Recent advances in cancer biology have led to the identification of new targets in neoplastic cells and the development of novel targeted therapies. At this time, two targeted agents are approved by the FDA in advanced non-small cell lung cancer (NSCLC): the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib, and the anitangiogenic bevacizumab. A third agent, cetuximab, which was recently shown to enhance survival when used with cisplatin and vinorelbine as first line therapy for advanced NSCLC, will likely be approved by regulatory agencies. With more than 500 molecularly targeted agents under development, the prospects of identifying novel therapies that benefit individual patients with lung cancer are bright.
Prognostic value of metastin expression in human pancreatic cancer
Authors: Nagai Kazuyuki , Doi Ryuichiro , Katagiri Fumihiko , Ito Tatsuo , Kida Atsushi , Koizumi Masayuki , Masui Toshihiko , Kawaguchi Yoshiya , Tomita Kenji , Oishi Shinya , Fujii Nobutaka , Uemoto Shinji
Published: January 2009

Background

KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood.

Methods

We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay.

Results

Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02). Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03), and the patients with a high plasma metastin level (n = 6) did not die after surgical resection.

Conclusion

Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.
Professional indemnity insurance and the uninsured practitioner
Authors: Holl-Allen Jonathan
Published: January 2009

The obligation on medical and dental professionals to be insured or adequately protected against claims is currently a professional obligation only. It will however shortly become a statutory obligation under amendments to the Medical Act 1983 and the Dentists Act 1984. Under existing arrangements protection against claims is provided by defence organizations on both contractual and discretionary bases. The uncooperative or uninsured practitioner may cause real difficulty to a Claimant with a valid claim. In some circumstances it will be possible to identify another person or body which is insured or protected and which bears responsibility in law for the acts and omissions of the uninsured practitioner, but in the primary care context, practitioners tend to be independent contractors and not employees. It is arguable that practice principals owe a duty to patients to ensure that locums and associates are adequately insured.
Characterization of a heat-stable enzyme possessing GTP-dependent RNA ligase activity from a hyperthermophilic archaeon,Pyrococcus furiosus
Authors: Kanai Akio , Sato Asako , Fukuda Yoko , Okada Kiyoshi , Matsuda Takashi , Sakamoto Taiichi , Muto Yutaka , Yokoyama Shigeyuki , Kawai Gota , Tomita Masaru
Published: January 2009

Using an expression protein library of a hyperthermophilic archaeon,Pyrococcus furiosus, we identified a gene (PF0027) that encodes a protein with heat-stable cyclic nucleotide phosphodiesterase (CPDase) activity. ThePF0027gene encoded a 21-kDa protein and an amino acid sequence that showed ∼27% identity to that of the 2′-5′ tRNA ligase protein, ligT (20 kDa), fromEscherichia coli. We found that the purified PF0027 protein possessed GTP-dependent RNA ligase activity and that synthetic tRNA halves bearing 2′,3′-cyclic phosphate and 5′-OH termini were substrates for the ligation reaction in vitro. GTP hydrolysis was not required for the reaction, and GTPγS enhanced the tRNA ligation activity of PF0027 protein, suggesting that the ligation step is regulated by a novel mechanism. In comparison to the strong CPDase activity of the PF0027 protein, the RNA ligase activity itself was quite weak, and the ligation product was unstable during in vitro reaction. Finally, we used NMR to determine the solution structure of the PF0027 protein and discuss the implications of our results in understanding the role of the PF0027 protein.
Splicing of designer exons reveals unexpected complexity in pre-mRNA splicing
Authors: Zhang Xiang H.-F. , Arias Mauricio A. , Ke Shengdong , Chasin Lawrence A.
Published: January 2009

Pre-messengerRNA (mRNA) splicing requires the accurate recognition of splice sites by the cellular RNA processing machinery. In addition to sequences that comprise the branchpoint and the 3′ and 5′ splice sites, the cellular splicing machinery relies on additional information in the form of exonic and intronic splicing enhancer and silencer sequences. The high abundance of these motifs makes it difficult to investigate their effects using standard genetic perturbations, since their disruption often leads to the formation of yet new elements. To lessen this problem, we have designed synthetic exons comprised of multiple copies of a single prototypical exonic enhancer and a single prototypical exonic silencer sequence separated by neutral spacer sequences. The spacer sequences buffer the exon against the formation of new elements as the number and order of the original elements are varied. Over 100 such designer exons were constructed by random ligation of enhancer, silencer, and neutral elements. Each exon was positioned as the central exon in a 3-exon minigene and tested for exon inclusion after transient transfection. The level of inclusion of the test exons was seen to be dependent on the provision of enhancers and could be decreased by the provision of silencers. In general, there was a good quantitative correlation between the proportion of enhancers and splicing. However, widely varying inclusion levels could be produced by different permutations of the enhancer and silencer elements, indicating that even in this simplified system splicing decisions rest on complex interplays of yet to be determined parameters.
Local government and structural crisis: an interpretive approach
Authors: Orr Kevin
Published: January 2009

This article examines ideas of local government crisis in the UK aiming to apply macrolevel political economy debates to this sector. Two observations underpin its rationale. The first concerns structuralism's neglect of local government and the disconnection from its lively history of crisis discourses. Crisis discourses are a key frame through which local government actors have come to understand their environment. The second is that the fast-growing literature on crisis leadership says little about the underlying causes of crises. The article synthesises a political-sociological interest in crisis with the grounded focus of interpretivism to offer insights about context and practice.
"Wait for the Next Pictures": Intertextuality and Cliffhanger Continuity in Early Cinema and Comic Strips
Authors: Lambert Josh
Published: January 2009

Harry Hershfield's "Desperate Desmond" exemplifies the intertextuality of sensational melodrama in the 1910s, especially between motion pictures and comic strips. Documenting Hershfield's sources and analyzing the narrative strategies of his strip and its motion picture adaptations, this essay theorizes "cliffhanger continuity" as a special, commercially expedient feature of serial publication.
Down and Out in Negishi: Reclusion and Struggle in an Edo Suburb
Authors: Brecher W. Puck
Published: January 2009

As administratively ambiguous zones, suburbs in early modern Japan (1600–1868) became favored as secluded sites conducive to self-reinvention. The community occupying Negishi in the eighteenth and nineteenth centuries provides an apt case study of how, in violation of segregation laws, individuals from all status groups came to live together in privatized outlying aesthetic spaces. The result was the emergence of a comparatively horizontal, egalitarian, and self-sustaining community that embraced and challenged contemporary utopian representations of meisho (celebrated spots). Documents produced by Negishi residents reveal an array of living experiences that complicate, and occasionally subvert, our view of suburban spaces and lifestyles.
A Revolution in Military Cartography?: Europe 1650-1815
Authors: Black Jeremy
Published: January 2009

Military cartography is studied in order to approach the role of information in war. This serves as an opportunity to reconsider the Military Revolution and in particular changes in the eighteenth century. Mapping is approached not only in tactical, operational and strategic terms, but also with reference to the mapping of war for public interest. Shifts in the latter reflect changes in the geography of European conflict.
The Danger of Militarization in an Endless "War" on Terrorism
Authors: Kohn Richard H.
Published: January 2009

Since the early 1930s, the United States has become significantly militarized in government, economy, society, and culture. While never quite slipping over the edge into militarism either in behaviors, policies, or norms and values, the American people's identification with and use of war images and thinking, and a belief in the primacy of standing military forces for American safety, have become normalized. The danger of an endless "war" on terrorism is that the militarization common to America society in wartime will become permanent, infecting the country with militarism, and transforming the United States incrementally, over time, into a nation its founders would recognize, but abhor.
From Yuanqi (Primal Energy) to Wenqi (Literary Pneuma): A Philosophical Study of a Chinese Aesthetic
Authors: Gu Ming Dong
Published: January 2009

Wenqi 文氣 (literary pneuma) is a foundational idea in Chinese aesthetics. It has remained elusive since its initial formulation, however. This is so largely because previous scholars did not examine its ontological and epistemological conditions in analytic terms, still less explore its implications in a conceptual framework of artistic creation. Here, it is proposed to explore its general as well as specific implications against the larger background of Chinese intellectual thought and in relation to contemporary theories of literature and aesthetics. Through a philosophical inquiry, wenqi is here reconceived as an integration of the primal energy of the universe, the creative energy of human beings, and the totalizing force that animates an artistic work. Wenqi is viewed not as a substance or a product but as a creative and shaping force that flows from the writer into his writing, gives it a distinct shape, and makes it different from any other writing. The theory of wenqi is a system of aesthetic principles that govern the creative and shaping force operating in the space of three intertwined entities: the macrocosm of the universe including human society, the microcosm of the writer, and the microcosm of his writing.
Prolonged Treatments With Antiresorptive Agents and PTH Have Different Effects on Bone Strength and the Degree of Mineralization in Old Estrogen-Deficient Osteoporotic Rats
Authors: Cheng Zhiqiang , Yao Wei , Zimmermann Elizabeth A , Busse Cheryl , Ritchie Robert O , Lane Nancy E
Published: January 2009

Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. We hypothesize that bone active agents improve bone strength in osteoporotic bone by altering different material properties of the bone. Eighteen-month-old female Fischer rats were ovariectomized (OVX) or sham-operated and left untreated for 60 days to induce osteopenia before they were treated with single doses of either risedronate (500 μg/kg, IV), zoledronic acid (100 μg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1–34) (25 μg/kg, SC, three times per week), or vehicle (NS; 1 ml/kg, three times per week). Groups of animals were killed after days 60 and 180 of treatment, and either the proximal tibial metaphysis or lumbar vertebral body were studied. Bone volume and architecture were assessed by μCT and histomorphometry. Measurements of bone quality included the degree of bone mineralization (DBM), localized elastic modulus, bone turnover by histomorphometry, compression testing of the LVB, and three-point bending testing of the femur. The trabecular bone volume, DBM, elastic modulus, and compressive bone strength were all significantly lower at day 60 post-OVX (pretreatment, day 0 study) than at baseline. After 60 days of all of the bone active treatments, bone mass and material measurements agent were restored. However, after 180 days of treatment, the OVX + PTH group further increased BV/TV (+30% from day 60, p < 0.05 within group and between groups). In addition, after 180 days of treatment, there was more highly mineralized cortical and trabecular bone and increased cortical bone size and whole bone strength in OVX + PTH compared with other OVX + antiresorptives. Treatment of estrogen-deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength. However, prolonged treatment for 180 days with PTH resulted in additional gains in bone quality and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.
Photoreceptor Neurons Find New Synaptic Targets When Misdirected by OverexpressingruntinDrosophila
Authors: Edwards Tara N. , Meinertzhagen Ian A.
Published: January 2009

As a neuron differentiates, it adopts a suite of features specific to its particular type. Fly photoreceptors are of two types: R1–R6, which innervate the first optic neuropile, the lamina; and R7–R8, which innervate the second, the medulla. Photoreceptors R1–R6 normally have large light-absorbing rhabdomeres, express Rhodopsin1, and have synaptic terminals that innervate the lamina. InDrosophila melanogaster, we used the yeastGAL4/UASsystem to drive exogenous expression of the transcription factor Runt in subsets of photoreceptors, resulting in aberrant axonal pathfinding and, ultimately, incorrect targeting of R1–R6 synaptic terminals to the medulla, normally occupied by terminals from R7 and R8. Even when subsets of their normal R1–R6 photoreceptor inputs penetrate the lamina, to terminate in the medulla, normal target cells within the lamina persist and maintain expression of cell-specific markers. Some R1–R6 photoreceptors form reciprocal synaptic inputs with their normal lamina targets, whereas supernumerary terminals targeted to the medulla also form synapses. At both sites, tetrad synapses form, with four postsynaptic elements at each release site, the usual number in the lamina. In addition, the terminals at both sites are invaginated by profiles of glia, at organelles called capitate projections, which in the lamina are photoreceptor sites of vesicle endocytosis. The size and shape of the capitate projection heads are identical at both lamina and medulla sites, although those in the medulla are ectopic and receive invaginations from foreign glia. This uniformity indicates the cell-autonomous determination of the architecture of its synaptic organelles by the presynaptic photoreceptor terminal.
Calcium Current Diversity in Physiologically Different Local Interneuron Types of the Antennal Lobe
Authors: Husch Andreas , Paehler Moritz , Fusca Debora , Paeger Lars , Kloppenburg Peter
Published: January 2009

Behavioral and physiological studies show that neuronal interactions among the glomeruli in the insect antennal lobe (AL) take place during the processing of odor information. These interactions are mediated by a complex network of inhibitory and excitatory local interneurons (LNs) that restructure the olfactory representation in the AL, thereby regulating the tuning profile of projection neurons. InPeriplaneta americana, we characterized two LN types with distinctive physiological properties: (1) type I LNs that generated Na+-driven action potentials on odor stimulation and exhibited GABA-like immunoreactivity (GLIR) and (2) type II LNs, in which odor stimulation evoked depolarizations, but no Na+-driven action potentials (APs). Type II LNs did not express voltage-dependent transient Na+currents and accordingly would not trigger transmitter release by Na+-driven APs. Ninety percent of type II LNs did not exhibit GLIR. The distinct intrinsic firing properties were reflected in functional parameters of their voltage-activated Ca2+currents (ICa). Consistent with graded synaptic release, we found a shift in the voltage for half-maximal activation ofICato more hyperpolarized membrane potentials in the type II LNs. These marked physiological differences between the two LN types imply consequences for their computational capacity, synaptic output kinetics, and thus their function in the olfactory circuit.