bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent Outpatient Nesiritide Infusion Reduces Hospital Admissions in Patients With Advanced Heart Failure
Authors: Schwarz Ernst R. , Najam Sabeen , Akel Rami , Sulimanjee Nasir , Bionat Susan , Rosanio Salvatore
Published: September 2007

Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 ± 0.8 vs 3.6 ± 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 ± 870 vs 1092 ± 978 pg/mL, P = .95), blood urea nitrogen levels (45 ± 28 vs 45 ± 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 ± 0.85 vs 1.1 ± 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.
Supernormal Conduction in the Anomalous Bundles of the Wolff-Parkinson-White Syndrome: An Overlooked Electrophysiologic Property With Potential Clinical Implications
Authors: Chiale Pablo A. , Albino Ernesto , Garro Hugo A. , Selva Horacio , Levi Raúl J. , Sánchez Rubén A. , Elizari Marcelo V. , Álvarez Carlos B.
Published: September 2007

The anterograde refractory period (RP) of the accessory pathway (AP) is the main determinant factor of ventricular rate during atrial fibrillation in the Wolff-Parkinson-White (WPW) syndrome. We describe 3 examples of anterograde supernormal conduction (SNC) and 1 of retrograde SNC in APs. The paradoxical early recovery of propagation due to SNC, well inside a prolonged anterograde RP in the AP, may play a relevant role to determine the rate of ventricular response during atrial fibrillation, eventually leading to extremely fast ventricular rates, syncope, and even ventricular fibrillation in patients with WPW syndrome supposed a priori to be exposed to a low risk of sudden cardiac death. This may require very precise conditions, including an enhanced adrenergic influence on the heart. Retrograde SNC in APs may also participate in the mechanism of paroxysmal supraventricular tachycardias that are not easily induced by programmed cardiac stimulation.
Implantable Cardioverter Defibrillator Therapy and the Need for Concomitant Antiarrhythmic Drugs
Authors: Singh Steven , Murawski Matthew M.
Published: September 2007

Implantable cardioverter defibrillators (ICDs) are increasingly used for the prevention of sudden cardiac death in patients with life-threatening ventricular arrhythmias (VAs); however, there is a potential for severe and debilitating anxiety caused by symptoms associated with ICD therapy and anticipation of shocks. Anxiety is a psycho-logic stressor, including physiologic components that may lead to adrenergic excitation triggering new arrhythmias and ICD therapies. This often requires concomitant antiarrhythmic medication to reduce the frequency of shocks and symptomatic arrhythmias treated by anti-tachycardia pacing. Although published studies have documented the efficacy of currently available antiarrhythmics, they have limitations in patients with heart failure, may affect the defibrillation threshold, and/or have been associated with major side-effects. In conclusion, for the patient with an ICD experiencing symptomatic ventricular tachycardia (VTs) episodes or ICD shocks, there is a need for pharmacologic therapy to reduce the incidence of such events without affecting the performance of the ICD or causing major side-effects.
Diabetes Health Disparities
Authors: Peek Monica E. , Cargill Algernon , Huang Elbert S.
Published: September 2007

Racial and ethnic minorities bear a disproportionate burden of the diabetes epidemic; they have higher prevalence rates, worse diabetes control, and higher rates of complications. This article reviews the effectiveness of health care interventions at improving health outcomes and/or reducing diabetes health disparities among racial/ethnic minorities with diabetes. Forty-two studies met inclusion criteria. On average, these health care interventions improved the quality of care for racial/ethnic minorities, improved health outcomes (such as diabetes control and reduced diabetes complications), and possibly reduced health disparities in quality of care. There is evidence supporting the use of interventions that target patients (primarily through culturally tailored programs), providers (especially through one-on-one feedback and education), and health systems (particularly with nurse case managers and nurse clinicians). More research is needed in the areas of racial/ethnic minorities other than African Americans and Latinos, health disparity reductions, long-term diabetes-related outcomes, and the sustainability of health care interventions over time.
The Media's Role in a Clash of Misconceptions: The Case of the Danish Muhammad Cartoons
Authors: Hussain Ali J.
Published: September 2007

The Danish cartoon furor of early 2006 was only the most recent episode cited as evidence of a “clash of civilizations.” Although the subject was extensively reported by the global media, the media's framing of the debate as being between free speech and religious sensitivities was inherently flawed and contributed to further confusion rather than clarification. Moreover, the framework established and perpetuated by the media, that of a debate between freedom of speech and religious sensitivities, obscured the root cause of this conflict: the fact that both the Muslim world and the Western world suffer from gross misconceptions of the other. Although the misconceptions held by the Muslim world are phenomena that are, in relative terms, both more recent and more easily resolved, their counterparts in the Western world have been deeply embedded in the consciousness of Western society for more than a thousand years.This study examines the role of centuries of European media self-censorship on the subject of Muhammad in the most recent episode in this ongoing clash of misconceptions.
Specialist health promotion as a career choice in public health
Authors: Coen Caroline , Wills Jane
Published: September 2007

Aims: Health promotion is a young discipline and area of practice that has struggled to establish a discrete identity but which is becoming consolidated as a specialist field of practice through the establishment of occupational standards, a voluntary register (UKVR) and a multidisciplinary public health career framework. This study sought to explore current health promotion managers' career pathways into health promotionand their perceptions of their career future within a public health workforce.

Methods: This exploratory study used semi-structured interviews, a stimulus vignette and a standardized questionnaire to explore the career pathways and motivations of specialist health promotion managers at this time of considerable change in the professional project of public health and health promotion in the United Kingdom.

Results: Specialist health promotion managers express a lack of role clarity and loss of control over the developments of their profession. This is compounded by a perceived lack of external credibility of health promotion and by the difficulties health promotion has in justifying itself in modern economic evaluative frameworks and establishing its legitimacy as an equal partner service within public health organizations. Recent moves to professionalize health promotion within the regulation of the public health workforce were not embraced by these participants for whom the consequent occupational closure was seen as restricting role independence and autonomy, and not necessarily enhancing occupational status.

Conclusions: This study revealed that, currently, health promotion managers experience a lack of role clarity in their work and are uncertain about future career pathways in public health. Health promotion managers (not working at assistant level) do not readily identify with public health as a profession, or with the UKVR's `defined health promotion specialist' accreditation process. The career choices and motivations of health promotion managers shed some light on the future of the `specialist health promotion' workforce and how this may be structured.
Becoming a Music Student Investigating the skills and attitudes of students beginning a Music degree
Authors: Burland Karen , Pitts Stephanie
Published: September 2007

This article reports a project designed to foster first-year music students' academic study skills and to investigate their expectations and experiences of starting at university. Data gathered through questionnaires, diaries and in-class tasks reveal the change in learning strategies and musical identity the students experience in their first semester of the music degree course. Academic work and anxieties about workload and assessment challenge the focus on performing which has previously been the students' main source of musical involvement, necessitating a redefinition of what it means to be musically successful. These findings are discussed in the broader context of musicians' life-span development, and the article concludes with some implications for practice in higher education and beyond.
The Rights of Others and the Boundaries of Democracy
Authors: Bauböck Rainer
Published: September 2007

Benhabib argues that the tension between universal human rights and democratic self-determination cannot be resolved. Distinguishing between the principle of rights, on the one hand, and context-specific `schedules of rights', on the other hand, helps, however, to specify the scope of both norms. I show that applying this idea to questions of citizenship requires further elaboration in three respects: (1) Benhabib's argument for porous rather than open borders, which does not fully address the challenge of global distributive justice; (2) norms for access to citizenship, which need to cover also transnational affiliations between sending states and their external populations; and (3) necessary constraints on democratic self-determination. I suggest replacing the principle of self-determination with a principle of self-government that does not include a unilateral right to determine the territorial or membership boundaries of the polity.
An Implementation of the Method of Aperture Meridians for the ISO/CIE Standard General Sky
Authors: Roy GG , Kittler R. , Darula S.
Published: September 2007

The use of the new ISO/CIE Standard General Sky offers some new challenges for lighting designers. The MAMmodeller package described in this study provides a user-friendly tool for visualizing each of the SSLD 15 models in simple design contexts. The method of aperture meridians (MAM) provides a relatively simple geometric framework to estimate the appearance of the sky as a luminance map in the window opening, as seen from a point of interest inside the room. In addition, the total horizontal illuminance at the same point is estimated. This provides the user or designer with a quick tool for undertaking preliminary design investigations. MAMmodeller is not a complete lighting design tool, it considers only sunlight and the diffuse light component from the sky entering through the window opening. It does not account for internal reflections, artificial lighting, or external reflections.
Accelerated atherogenesis and neointima formation in heparin cofactor II–deficient mice
Authors: Vicente Cristina P. , He Li , Tollefsen Douglas M.
Published: September 2007

Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin when bound to dermatan sulfate or heparin. HCII-deficient mice are viable and fertile but rapidly develop thrombosis of the carotid artery after endothelial injury. We now report the effects of HCII deficiency on atherogenesis and neointima formation. HCII-null or wild-type mice, both on an apolipoprotein E–null background, were fed an atherogenic diet for 12 weeks. HCII-null mice developed plaque areas in the aortic arch approximately 64% larger than wild-type mice despite having similar plasma lipid and glucose levels. Neointima formation was induced by mechanical dilation of the common carotid artery. Thrombin activity, determined by hirudin binding or chromogenic substrate hydrolysis within 1 hour after injury, was higher in the arterial walls of HCII-null mice than in wild-type mice. After 3 weeks, the median neointimal area was 2- to 3-fold greater in HCII-null than in wild-type mice. Dermatan sulfate administered intravenously within 48 hours after injury inhibited neointima formation in wild-type mice but had no effect in HCII-null mice. Heparin did not inhibit neointima formation. We conclude that HCII deficiency promotes atherogenesis and neointima formation and that treatment with dermatan sulfate reduces neointima formation in an HCII-dependent manner.
Immunotherapy of B-cell malignancies: first MABs, now SMIPs
Authors: Furman Richard R. , Leonard John P.
Published: September 2007

Zhao and colleagues report on a novel small modular immunopharmaceutical (SMIP) directed against CD37 in chronic lymphocytic leukemia (CLL). This agent offers several potential design advantages, and demonstrates interesting preclinical activity through mechanisms of action different from standard therapies.
Tissue factor needs a “complement”
Authors: McCrae Keith R.
Published: September 2007

Redecha and colleagues demonstrate a requirement for both tissue factor and complement in this elegant investigation into the mechanisms of aPL-associated fetal loss.
OX40 costimulation and regulatory T cells
Authors: Kupiec-Weglinski Jerzy W.
Published: September 2007

The OX40 T-cell costimulatory molecule, critical for both survival and proliferation of activated T cells, has now been identified as a key negative regulator of Foxp3+ T regulatory cells (Tregs).
Progression risk for MGUS and SMM
Authors: Greipp Philip
Published: September 2007

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at continuous risk of progression. Each year, 1% progress, usually to active multiple myeloma (MM).1 Such patients must be monitored for life. Asymptomatic smoldering multiple myeloma (SMM) has an even greater risk of progression to MM. Recently reported strategies improve our ability to estimate the risk of MM in these patients.
Lef-1: NOTCHed up in T-cell lymphomas
Authors: Gounari Fotini , Dose Marei
Published: September 2007

In this issue of Blood, Spaulding and colleagues show that Lef-1, one of the transcription factors mediating Wnt signaling, is a transcriptional target of Notch in T-cell lymphomas. Notch-activating mutations are commonly found in human T-lineage acute lymphoblastic leukemia (T-ALL) cases, while activation of Wnt/β-catenin signaling has recently been shown to induce T-cell leukemia in mice. The proposed regulation of Lef-1 transcription by Notch suggests the intriguing possibility that the Notch and Wnt pathways are closely intertwined in the etiology of T-cell leukemia.
Tortoise and hare win for SCD
Authors: Tisdale John F.
Published: September 2007

Bernaudin and colleagues report, in this issue of Blood, the long-term results of the largest study of related myeloablative stem-cell transplantation for sickle cell disease (SCD). Their results show that slow, steady improvements over time, along with the addition of rabbit anti–thymocyte globulin (ATG) to the conditioning regimen, combine to produce an event-free survival (EFS) of 95.3%. They argue that for children with a suitable sibling-matched donor, myeloablative transplantation should be considered the standard of care in those at high risk for stroke.
A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study
Authors: Hwang Shih-Jen , Yang Qiong , Meigs James B , Pearce Elizabeth N , Fox Caroline S
Published: September 2007

Background

Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP) set and measures of kidney function and endocrine traits.

Methods

Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981) were measured at the seventh examination cycle (1998–2001); GFR (n = 1010) was estimated via the Modification of Diet in Renal Disease (MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle (1995–1998) and was indexed to urinary creatinine (n = 822). Thyroid stimulating hormone (TSH) was measured at the third and fourth examination cycles (1981–1984; 1984–1987) and mean value of the measurements were used (n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE) and family-based association tests (FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value ≥ 0.001, and call rates of at least 80%.

Results

The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10-05), rs1158167 with cysC (p-value 8.5*10-09), rs1712790 with UAE (p-value 1.9*10-06), and rs6977660 with TSH (p-value 3.7*10-06), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10-5), rs563754 with cysC (p-value 4.7*10-5), rs1243400 with UAE (p-value 4.8*10-6), and rs4128956 with TSH (p-value 3.6*10-5), respectively. Detailed association test results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Four SNPs in or near the CST3 gene were highly associated with cysC levels (p-value 8.5*10-09 to 0.007).

Conclusion

Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
Temperature effect on tert-butyl alcohol (TBA) biodegradation kinetics in hyporheic zone soils
Authors: Greenwood Mark H , Sims Ronald C , McLean Joan E , Doucette William J
Published: September 2007

Background

Remediation of tert-butyl alcohol (TBA) in subsurface waters should be taken into consideration at reformulated gasoline contaminated sites since it is a biodegradation intermediate of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-butyl formate (TBF). The effect of temperature on TBA biodegradation has not been not been published in the literature.

Methods

Biodegradation of [U 14C] TBA was determined using hyporheic zone soil microcosms.

Results

First order mineralization rate constants of TBA at 5°C, 15°C and 25°C were 7.84 ± 0.14 × 10-3, 9.07 ± 0.09 × 10-3, and 15.3 ± 0.3 × 10-3 days-1, respectively (or 2.86 ± 0.05, 3.31 ± 0.03, 5.60 ± 0.14 years-1, respectively). Temperature had a statistically significant effect on the mineralization rates and was modelled using the Arrhenius equation with frequency factor (A) and activation energy (Ea) of 154 day-1 and 23,006 mol/J, respectively.

Conclusion

Results of this study are the first to determine mineralization rates of TBA for different temperatures. The kinetic rates determined in this study can be used in groundwater fate and transport modelling of TBA at the Ronan, MT site and provide an estimate for TBA removal at other similar shallow aquifer sites and hyporheic zones as a function of seasonal change in temperature.
Translational methods in biostatistics: linear mixed effect regression models of alcohol consumption and HIV disease progression over time
Authors: Finucane Mariel M , Samet Jeffrey H , Horton Nicholas J
Published: September 2007

Longitudinal studies are helpful in understanding how subtle associations between factors of interest change over time. Our goal is to apply statistical methods which are appropriate for analyzing longitudinal data to a repeated measures epidemiological study as a tutorial in the appropriate use and interpretation of random effects models. To motivate their use, we study the association of alcohol consumption on markers of HIV disease progression in an observational cohort. To make valid inferences, the association among measurements correlated within a subject must be taken into account.

We describe a linear mixed effects regression framework that accounts for the clustering of longitudinal data and that can be fit using standard statistical software. We apply the linear mixed effects model to a previously published dataset of HIV infected individuals with a history of alcohol problems who are receiving HAART (n = 197). The researchers were interested in determining the effect of alcohol use on HIV disease progression over time. Fitting a linear mixed effects multiple regression model with a random intercept and random slope for each subject accounts for the association of observations within subjects and yields parameters interpretable as in ordinary multiple regression. A significant interaction between alcohol use and adherence to HAART is found: subjects who use alcohol and are not fully adherent to their HIV medications had higher log RNA (ribonucleic acid) viral load levels than fully adherent non-drinkers, fully adherent alcohol users, and non-drinkers who were not fully adherent.

Longitudinal studies are increasingly common in epidemiological research. Software routines that account for correlation between repeated measures using linear mixed effects methods are now generally available and straightforward to utilize. These models allow the relaxation of assumptions needed for approaches such as repeated measures ANOVA, and should be routinely incorporated into the analysis of cohort studies.
Monitoring of oxidative and metabolic stress during cardiac surgery by means of breath biomarkers: an observational study
Authors: Pabst Florian , Miekisch Wolfram , Fuchs Patricia , Kischkel Sabine , Schubert Jochen K
Published: September 2007

Background

Volatile breath biomarkers provide a non-invasive window to observe physiological and pathological processes in the body. This study was intended to assess the impact of heart surgery with extracorporeal circulation (ECC) onto breath biomarker profiles. Special attention was attributed to oxidative or metabolic stress during surgery and extracorporeal circulation, which can cause organ damage and poor outcome.

Methods

24 patients undergoing cardiac surgery with extracorporeal circulation were enrolled into this observational study. Alveolar breath samples (10 mL) were taken after induction of anesthesia, after sternotomy, 5 min after end of ECC, and 30, 60, 90, 120 and 150 min after end of surgery. Alveolar gas samples were withdrawn from the circuit under visual control of expired CO2. Inspiratory samples were taken near the ventilator inlet. Volatile substances in breath were preconcentrated by means of solid phase micro extraction, separated by gas chromatography, detected and identified by mass spectrometry.

Results

Mean exhaled concentrations of acetone, pentane and isoprene determined in this study were in accordance with results from the literature. Exhaled substance concentrations showed considerable inter-individual variation, and inspired pentane concentrations sometimes had the same order of magnitude than expired values. This is the reason why, concentrations were normalized by the values measured 120 min after surgery. Exhaled acetone concentrations increased slightly after sternotomy and markedly after end of ECC. Exhaled acetone concentrations exhibited positive correlation to serum C-reactive protein concentrations and to serum troponine-T concentrations. Exhaled pentane concentrations increased markedly after sternotomy and dropped below initial values after ECC. Breath pentane concentrations showed correlations with serum creatinine (CK) levels. Patients with an elevated CK-MB (myocardial&brain)/CK ratio had also high concentrations of pentane in exhaled air. Exhaled isoprene concentrations raised significantly after sternotomy and decreased to initial levels at 30 min after end of ECC. Exhaled isoprene concentrations showed a correlation with cardiac output.

Conclusion

Oxidative and metabolic stress during cardiac surgery could be assessed continuously and non-invasively by means of breath analysis. Correlations between breath acetone profiles and clinical conditions underline the potential of breath biomarker monitoring for diagnostics and timely initiation of life saving therapy.
Exploration of the omics evidence landscape: adding qualitative labels to predicted protein-protein interactions
Authors: van Noort Vera , Snel Berend , Huynen Martijn A
Published: September 2007

Background

In the post-genomic era various functional genomics, proteomics and computational techniques have been developed to elucidate the protein interaction network. While some of these techniques are specific for a certain type of interaction, most predict a mixture of interactions. Qualitative labels are essential for the molecular biologist to experimentally verify predicted interactions.

Results

Of the individual protein-protein interaction prediction methods, some can predict physical interactions without producing other types of interactions. None of the methods can specifically predict metabolic interactions. We have constructed an 'omics evidence landscape' that combines all sources of evidence for protein interactions from various types of omics data for Saccharomyces cerevisiae. We explore this evidence landscape to identify areas with either only metabolic or only physical interactions, allowing us to specifically predict the nature of new interactions in these areas. We combine the datasets in ways that examine the whole evidence landscape and not only the highest scoring protein pairs in both datasets and find specific predictions.

Conclusion

The combination of evidence types in the form of the evidence landscape allows for qualitative labels to be inferred and placed on the predicted protein interaction network of S. cerevisiae. These qualitative labels will help in the biological interpretation of gene networks and will direct experimental verification of the predicted interactions.
The Dam1/DASH complex is required for the retrieval of unclustered kinetochores in fission yeast
Authors: Franco Alejandro , Meadows John C. , Millar Jonathan B. A.
Published: September 2007

In fission yeast centromeres cluster at the nuclear envelope in a region underlying the spindle pole body during interphase, an arrangement known as a Rabl configuration. We have identified a strain in which one pair of sister kinetochores is unclustered from the others and binds the nuclear envelope at a point distal to the spindle pole body. We show that during mitosis unclustered kinetochores are captured by intranuclear spindle microtubules which then pull the kinetochores back to one of the two spindle poles before they are bi-oriented on the mitotic spindle. We find that kinetochore retrieval occurs at the depolymerising microtubule plus end and is dependent on the non-essential Dam1/DASH complex. In the absence of Dam1 unclustered kinetochores are captured on the lateral surface of spindle microtubule bundles but poleward kinetochore movement does not occur. These data provide the first direct evidence that the Dam1/DASH complex can couple the force generated by microtubule depolymerisation to direct chromosome movement in vivo.
Stator-clocking effects on the unsteady interaction of secondary flows in a 1.5-stage unshrouded turbine
Authors: Behr T , Kalfas A. I. , Abhari R. S.
Published: September 2007

Effects of stator clocking on the unsteady interaction of stator and rotor secondary flows and performance are investigated in a 1.5-stage, high-pressure turbine. Due to the low aspect ratio design of the blade rows, vortical structures dominate the inlet flow field of the second stator row. Therefore the interaction of first stator and rotor secondary flows in relation to the stator-clocking position must be considered in order to achieve an optimized multi-stage performance.

Four different stator-clocking positions are studied in this experimental investigation. The data comprise unsteady and steady probe measurements, which are acquired downstream of the rotor and the second stator blade row of a 1.5-stage, unshrouded turbine. A two-sensor fast response aerodynamic probe technique is used in the measurement campaign.

It is found that multi-row interaction effects of vortical secondary flow features dominate the loss creation in turbine stages having low aspect ratio geometries. The periodic interaction of shed passage vortices of the first stator with secondary flow structures of the rotor creates regions characterized by reduced total pressure and increased turbulence, and entropy at fixed locations relative to the subsequent stator. Circumferential position of these interaction regions defines the spanwise distribution of total pressure loss in the downstream stator. Stator-clocking controls the spanwise distribution of loss in high-pressure turbines. However, the potential of reducing the loss is limited due to the three-dimensional nature of the flow, and hence, the non-uniform effect of a clocking position on the spanwise performance of a downstream stator.
Predicted and measured performance and stability of two variants of a military fan
Authors: Ginder R. B. , Calvert W. J. , Emmerson P. R.
Published: September 2007

Adequate stability margin is a key issue in the design of compact, highly loaded transonic fans needed for future combat engines, especially for operation with high levels of inlet distortion. Stability prediction is difficult, and modern three-dimensional multi-row flow calculation methods are being increasingly applied. Following a fairly comprehensive review of previous such applications, this paper describes studies on baseline and redesigned versions of an advanced fan stage. The predictions capture the main features of the test results, including the increased stability margin of the revised design. The results indicate that whereas the critical region affecting surge for the baseline case is the rotor tip, the stability of the revised stage design can be affected by the stator, and a mechanism for this is suggested. Further insight is gained from solutions using a closely-coupled, choked-nozzle exit boundary condition and from calculations with radial total pressure distortion at inlet, including its development from an upstream generating screen.
Protein Adsorption is Dependent on Substrate Polymer Polymorphs
Authors: Matsuno Hisao , Nagasaka Yuya , Kurita Kimio , Serizawa Takeshi
Published: September 2007

Adhesion force, quartz crystal microbalance (QCM), and attenuated total reflection infrared (ATR-IR) measurements revealed that native proteins weakly adsorbed onto poly(lactide) (PLA) stereocomplexes with 31 helical (β-form) crystals when compared with poly(l-lactide) (PLLA) homogeneous crystals with 103 helical (α-form) crystals. These observations suggest that substrate polymer polymorphs can be significant factors that determine protein-adsorptive properties.
Dispersion of Layered Hexaniobate in Organic Solvents through Silylation and Liquid Crystalline Behavior of the Colloidal Suspension
Authors: Nakato Teruyuki , Hashimoto Sachika
Published: September 2007

Layered niobate K4Nb6O17 became compatible to organic solvents through grafting octadecyltrimethoxysilane onto the niobate layers. The silylated niobate was stably dispersed in chloroform and finitely swelled in toluene whereas the niobate intercalated with dodecylammonium ions was settled out in both the solvents. Colloids of the silylated niobate dispersed in chloroform exhibited lyotropic liquid crystallinity at high niobate concentrations.
Elimination of Isocyanate and Isothiocyanate Molecules at the Electrospray Ionization Ion Trap, Electrospray Ionization Quadrupole Time-of-Flight and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectrometry Fragmentation of Sodium Cationized Brassitin, Brassinin and Their Glycosides
Authors: Bekešová Slávka , Kováčik Vladimír , Tvaroška Igor , Čurillová Zuzana , Škultéty Ľudovít , Řehulka Pavel
Published: September 2007

Fragmentation mechanisms of phytoalexin analogs, including brassitin and brassinin and their glucosylated analogs, have been studied by electrospray (ESI) ion trap (IT) multistage (MS n, n = 1–4) mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF/ToF) and ESI-Q/ToF tandem mass spectrometry techniques. At the fragmentation of sodium adducts a hitherto not described process has been elucidated The proposed mechanism of this process includes cyclization of the brassitin and brassinin cationized adducts through a six-membered cycle of the molecules and the elimination of isocyanate or isothiocyanate from the thio- or dithiocarbamate moiety, giving rise to [M + Na – 43]+ or [M + Na – 59]+ adducts. The elimination of NH=C=O or NH=C=S molecules has been confirmed by the high resolution measurement of the elemental composition of the ions produced and quantum-chemical calculations of the six-membered transition state. Other fragmentation routes include cleavage of an alkane linker, while numerous characteristic hexopyranose pathways are taking place in the glucosylated compounds. The presented theoretical data on the ESI and MALDI behavior of the saccharidic, as well as of the indole aglycon parts, can facilitate structural elucidation of the analogous compounds.
Matrix-Assisted Laser Desorption/Ionization Studies on Transition Metal Complexes of Benzimidazole Thiosemicarbazones
Authors: Bhaskar G. , Prabhakar S. , Raju N. Prasada , Ramanjaneyulu G.S.R.
Published: September 2007

The transition metal (M=Fe, Co, Ni, Cu, Zn, Cd and Hg) complexes of 2-acetylbenzimidazolethiosemicarbazone (L1) and 1-methyl 2-acetylbenzimidazolethiosemicarbazone (L2) were analyzed by matrix-assisted laser desorption/ionization (MALDI) using 2-cyano-4-hydroxycinnamic acid (HCCA), terthiophene (THP), methyl 5-(4-methoxy-1-naphthyl)-(2E,4E)-2,4-pentadienoate (MMNPD) and 2,7-dimethoxy naphthalene (DMN) as the matrices. All the MALDI spectra are clean without any contribution from the complex ions resulted by multiple proton addition/removal. All the complexes, except Cu, irrespective of the matrix used, show 1:2 complex ions wherein two ligands (neutral or deprotonated) complex with the metal ion depending on the nature and stable oxidation state of the central metal ion viz., [M + 2L – 2H]+ ion for Fe and Co complexes (+3 oxidation state) and [M + 2L – H]+ ion for Ni, Zn, Cd and Hg (+2 oxidation state). The Cu complex shows 1:1 complex ions corresponding to [2M + 2L – 2H]+ ions. When HCCA is used as a matrix, the complex ions due to ligand exchange by matrix are also found, and this process is relatively more if a neutral ligand is bound to the metal ion in the original complex ion. The type of complex ions found under MALDI experiments are similar to those found under electrospray ionization experiments. However, the complex ions due to reduction of Cu are found only in the MALDI analysis of Cu complexes.
Research Note—Strategic Bid-Shading and Sequential Auctioning with Learning from Past Prices
Authors: Zeithammer Robert
Published: September 2007

This paper analyzes sequential auctioning of single units of an indivisible good to a fluctuating population composed of overlapping generations of unit-demand bidders. Two phenomena emergent in such a market are investigated: forward-looking bidding strategies, and closed-loop selling strategies that involve learning from past prices. The buyers shade their bids down, i.e., bid less than they would in a single isolated auction, whenever they expect the seller to sell another unit of the good in the near future. Unlike in exogenous sequences of auctions, the optimal bidding strategy thus depends on the seller's selling strategy. The converse dependence also occurs: the seller can learn about current demand from past realized prices, and sell only in periods with high-enough demand. Such learning depends on the extent of bid-shading because the seller needs to invert the bidding strategy to learn. In equilibrium, buyer bid-shading persists even when the seller does not sell in every period, but it is self-regulating in that it eventually vanishes when the existence of the market is threatened by low seller profits. In this sense, auction markets have a “self-preservation instinct.” General properties of learning about current demand from past auction prices are also investigated and characterized.
A Single-Product Inventory Model for Multiple Demand Classes
Authors: Arslan Hasan , Graves Stephen C. , Roemer Thomas A.
Published: September 2007

We consider a single-product inventory system that serves multiple demand classes, which differ in their shortage costs or service-level requirements. We assume a critical-level control policy, and a backorder clearing mechanism in which we treat a backorder for a lower-priority class equivalent to a reserve-stock shortfall for the higher-priority class. We show the equivalence between this inventory system and a serial inventory system. Based on this equivalence, we develop a model for cost evaluation and optimization under the assumptions of Poisson demand, deterministic replenishment lead time, and a continuous-review (Q, R) policy with rationing. We propose a computationally efficient heuristic and develop a bound on its performance. We provide a numerical experiment to show the effectiveness of the heuristic and the value from a rationing policy. Finally, we describe how to extend the model to permit service times, and how to extend the model to a multi-echelon setting.
Valuing R&D Projects in a Portfolio: Evidence from the Pharmaceutical Industry
Authors: Girotra Karan , Terwiesch Christian , Ulrich Karl T.
Published: September 2007

Understanding the value of a product development project is central to a firm's choice of project portfolio. The value of a project to a firm depends not only on its properties but also on the other projects being developed by the firm. This is due to interactions with the other projects that address the same consumer need and require the same development resources. In this study, we empirically investigate the structure and significance of these portfolio-level project interactions. Using a self-developed pharmaceutical industry data set, we conduct an event study around the failure of phase III clinical trials and their effect on the market valuation of the firm. The study exploits the natural experiment of a product development failure to give us a measure of the value of a drug development project to a firm. We then explain the variance in the value of projects based on interactions with other projects in the firm's portfolio. We find that the presence of other projects targeting the same market and a build-up of projects that require the same development resources reduce the value of a development project. In addition to providing evidence on the significance and structure of these portfolio-level project interactions, the empirical model estimated in this paper also provides a data-driven approach to valuing projects that may be relevant to licensing transactions.
Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum
Authors: Yavich Leonid , Forsberg Markus M. , Karayiorgou Maria , Gogos Joseph A. , Männistö Pekka T.
Published: September 2007

Accumulating evidence from clinical and preclinical studies shows that catechol-O-methyltransferase (COMT) plays a significant role in dopamine metabolism in the prefrontal cortex, but not in the striatum. However, to what extent dopamine overflow in the prefrontal cortex and striatum is controlled by enzymatic degradation versus reuptake is unknown. We used COMT deficient mice to investigate the role of COMT in these two brain regions within vivovoltammetry. A real-time analysis of evoked dopamine overflow showed that removal of dopamine was twofold slower in the prefrontal cortex of mice lacking COMT than in wild-type mice, indicating that half of the dopamine decline in this brain region results from COMT-mediated enzymatic degradation. Lack of COMT did not influence dopamine overflow/decline in the dorsal striatum. COMT-deficient mice demonstrated a small (20–25%) but consistent increase in evoked dopamine release in the prefrontal cortex, but not in the dorsal striatum. Cocaine affected equally dopaminergic neurotransmission in the prefrontal cortex in both genotypes by prolonging 3–4 times dopamine elimination from extracellular space. Paradoxically, this happened without increase of the peak levels of evoked dopamine release. The present findings represent the first demonstration of the significant contribution of COMT in modulating the dynamics of dopamine overflow in the prefrontal cortex and underscore the therapeutic potential of manipulating COMT activity to alter dopaminergic neurotransmission in the prefrontal cortex.
Gonadotropin-Releasing Hormone Neurons Express KATPChannels That Are Regulated by Estrogen and Responsive to Glucose and Metabolic Inhibition
Authors: Zhang Chunguang , Bosch Martha A. , Levine Jon E. , Rønnekleiv Oline K. , Kelly Martin J.
Published: September 2007

Gonadotropin-releasing hormone (GnRH) is released in a pulsatile manner that is dependent on circulating 17β-estradiol (E2) and glucose concentrations. However, the intrinsic conductances responsible for the episodic firing pattern underlying pulsatile release and the effects of E2 and glucose on these conductances are primarily unknown. Whole-cell recordings from mouse enhanced green fluorescent protein-GnRH neurons revealed that the KATPchannel opener diazoxide induced an outward current that was antagonized by the sulfonylurea receptor 1 (SUR1) channel blocker tolbutamide. Single-cell reverse transcription (RT)-PCR revealed that the majority of GnRH neurons expressed Kir6.2 and SUR1 subunits, which correlated with the diazoxide/tolbutamide sensitivity. Also, a subpopulation of GnRH neurons expressed glucokinase mRNA, a marker for glucose sensitivity. Indeed, GnRH neurons decreased their firing in response to low glucose concentrations and metabolic inhibition. The maximum diazoxide-induced current was approximately twofold greater in E2-treated compared with oil-treated ovariectomized females. In current clamp, estrogen enhanced the diazoxide-induced hyperpolarization to a similar degree. However, based on quantitative RT-PCR, estrogen did not increase the expression of Kir6.2 or SUR1 transcripts in GnRH neurons. In the presence of ionotropic glutamate and GABAAreceptor antagonists, tolbutamide depolarized and significantly increased the firing rate of GnRH neurons to a greater extent in E2-treated females. Finally, tolbutamide significantly increased GnRH secretion from the preoptic-mediobasal hypothalamus. Therefore, it appears that KATPchannels and glucokinase are expressed in GnRH neurons, which renders them directly responsive to glucose. In addition, KATPchannels are involved in modulating the excitability of GnRH neurons in an estrogen-sensitive manner that ultimately regulates peptide release.
System xc−Activity and Astrocytes Are Necessary for Interleukin-1β-Mediated Hypoxic Neuronal Injury
Authors: Fogal Birgit , Li Jun , Lobner Doug , McCullough Louise D. , Hewett Sandra J.
Published: September 2007

The purpose of this study was to elucidate the cellular/biochemical pathway(s) by which interleukin-1β (IL-1β) contributes to the pathogenesis of hypoxic–ischemic brain damage.In vivo, IL-1 receptor type I (IL-1RI)-deficient mice showed smaller infarcts and less neurological deficits than wild-type animals after a 90 min reversible middle cerebral artery occlusion.In vitro, IL-1β mediated an enhancement of hypoxic neuronal injury in murine cortical cultures that was lacking in cultures derived from IL-1RI null mutant animals and was blocked by the IL-1 receptor antagonist or an IL-1RI blocking antibody. This IL-1β-mediated potentiation of hypoxic neuronal injury was associated with an increase in both cellular cystine uptake ([cystine]i) and extracellular glutamate levels ([glutamate]e) and was prevented by either ionotropic glutamate receptor antagonism or removal ofl-cystine, suggesting a role for the cystine/glutamate antiporter (System xc−). Indeed, dual System xc−/metabotropic glutamate receptor subunit 1 (mGluR1) antagonism but not selective mGluR1 antagonism prevented neuronal injury. Additionally, cultures derived from mGluR1-deficient mice exhibited the same potentiation in injury after treatment with IL-1β as wild-type cultures, an effect prevented by System xc−/mGluR1 antagonism. Finally, assessment of System xc−function and kinetics in IL-1β-treated cultures revealed an increase in velocity of cystine transport (Vmax), in the absence of a change in affinity (Km). Neither the enhancement in [cystine]i, [glutamate]e, or neuronal injury were observed in chimeric cultures consistingof IL-1RI+/+neurons plated on top ofIL-1RI−/−astrocytes, highlighting the importance of astrocyte-mediated alterations in System xc−as a novel contributor to the development and progression of hypoxic neuronal injury.
Interkinetic Nuclear Migration and the Selection of Neurogenic Cell Divisions during Vertebrate Retinogenesis
Authors: Baye Lisa M. , Link Brian A.
Published: September 2007

During retinal development, neuroepithelial progenitor cells divide in either a symmetric proliferative mode, in which both daughter cells remain mitotic, or in a neurogenic mode, in which at least one daughter cell exits the cell cycle and differentiates as a neuron. Although the cellular mechanisms of neurogenesis remain unknown, heterogeneity in cell behaviors has been postulated to influence this cell fate. In this study, we analyze interkinetic nuclear migration, the apical–basal movement of nuclei in phase with the cell cycle, and the relationship of this cell behavior to neurogenesis. Using time-lapse imaging in zebrafish, we show that various parameters of interkinetic nuclear migration are significantly heterogeneous among retinal neuroepithelial cells. We provide direct evidence that neurogenic progenitors have greater basal nuclei migrations during the last cell cycle preceding a terminal mitosis. In addition, we show that atypical protein kinase C (aPKC)-mediated cell polarity is essential for the relationship between nuclear position and neurogenesis. Loss of aPKC also resulted in increased proliferative cell divisions and reduced retinal neurogenesis. Our data support a novel model for neurogenesis, in which interkinetic nuclear migration differentially positions nuclei in neuroepithelial cells and therefore influences selection of progenitors for cell cycle exit based on apical–basal polarized signals.