bluuebunny/crossref_metadata_2025 huggingface dataset:
Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey
Authors: FAGÖ‐OLSEN CARSTEN L. , HØGDALL CLAUS , KEHLET HENRIK , CHRISTENSEN IB J. , OTTESEN BENT
Published: November 2010

Objective. This retrospective, nationwide, observational study was designed to compare treatment in tertiary referral centers vs. regional hospitals on overall survival for patients with stage IIIC and IV ovarian cancer. Material and methods. The study took place in all gynecological departments in Denmark, involving a total of 1,160 patients with stage IIIC or IV ovarian cancer. Data were extracted for 2,024 patients with all stages of ovarian cancer recorded in the Danish Gynecological Cancer Database between 1 January 2005 and 31 December 2008. The main outcome measure was overall survival. Results. No difference was found between tertiary centers and regional hospitals with regard to age, body mass index, American Society of Anesthesiologists score or comorbidity. Patients in regional hospitals had poorer Eastern Cooperative Oncology Group performance status, i.e.1.0 vs. 2.0 (p= 0.005). Patients in referral centers presented more often with stage IIIC and IV disease, i.e. 59.7 vs. 51.7% (p < 0.001). Patients with stage IIIC and IV disease in regional vs. tertiary hospitals had a higher rate of primary cytoreductive surgery, i.e. 89.5 vs. 82.5% (p= 0.004), a poorer rate of complete cytoreductive surgery following primary cytoreductive surgery, i.e. 13.9 vs. 25.2% (p < 0.001), a lower rate of neoadjuvant chemotherapy, i.e. 5.5 vs. 13.4% (p < 0.001), and more often underwent acute surgery, i.e. 17.0 vs. 9.2% (p < 0.001). Patients treated in referral centers had better overall survival (p= 0.021). Treatment in a referral center was an independent prognostic factor for overall survival hazard ratio, 0.83 (confidence interval 0.70–0.98). Conclusion. Patients with stage IIIC and IV ovarian cancer benefit from treatment in a tertiary referral center.
Species distribution models reveal apparent competitive and facilitative effects of a dominant species on the distribution of tundra plants
Authors: Pellissier Loïc , Anne Bråthen Kari , Pottier Julien , Randin Christophe F. , Vittoz Pascal , Dubuis Anne , Yoccoz Nigel G. , Alm Torbjørn , Zimmermann Niklaus E. , Guisan Antoine
Published: November 2010

Abiotic factors are considered strong drivers of species distribution and assemblages. Yet these spatial patterns are also influenced by biotic interactions. Accounting for competitors or facilitators may improve both the fit and the predictive power of species distribution models (SDMs). We investigated the influence of a dominant species, Empetrum nigrum ssp. hermaphroditum, on the distribution of 34 subordinate species in the tundra of northern Norway. We related SDM parameters of those subordinate species to their functional traits and their co‐occurrence patterns with E. hermaphroditum across three spatial scales. By combining both approaches, we sought to understand whether these species may be limited by competitive interactions and/or benefit from habitat conditions created by the dominant species. The model fit and predictive power increased for most species when the frequency of occurrence of E. hermaphroditum was included in the SDMs as a predictor. The largest increase was found for species that 1) co‐occur most of the time with E. hermaphroditum, both at large (i.e. 750 m) and small spatial scale (i.e. 2 m) or co‐occur with E. hermaphroditum at large scale but not at small scale and 2) have particularly low or high leaf dry matter content (LDMC). Species that do not co‐occur with E. hermaphroditum at the smallest scale are generally palatable herbaceous species with low LDMC, thus showing a weak ability to tolerate resource depletion that is directly or indirectly induced by E. hermaphroditum. Species with high LDMC, showing a better aptitude to face resource depletion and grazing, are often found in the proximity of E. hermaphroditum. Our results are consistent with previous findings that both competition and facilitation structure plant distribution and assemblages in the Arctic tundra. The functional and co‐occurrence approaches used were complementary and provided a deeper understanding of the observed patterns by refinement of the pool of potential direct and indirect ecological effects of E. hermaphroditum on the distribution of subordinate species. Our correlative study would benefit being complemented by experimental approaches.
Does the consumption of divergent resources influence risk taking behaviour in juvenile perch (Perca fluviatilis L.)?
Authors: Heynen M. , Heermann L. , Borcherding J.
Published: November 2010

Heynen M, Heermann L, Borcherding J. Does the consumption of divergent resources influence risk taking behaviour in juvenile perch (Perca fluviatilis L.)?  Ecology of Freshwater Fish 2011: 20: 1–4. © 2010 John Wiley & Sons A/S
The effects of topical application of bisphosphonates on replanted rat molars
Authors: Choi Sung Chul , Kwon Yong‐Dae , Kim Kwang Chul , Kim Gue‐Tae
Published: November 2010

Abstract –  The purpose of this study was to evaluate the potential usefulness of two bisphosphonates (BPs) (etidronate and zoledronate), compared with that of alendronate, which is a well‐known drug for delayed replantation, in decreasing or preventing inflammatory root resorption and replacement root resorption in replanted teeth. Eighty‐four Sprague Dawley rat maxillary first molars were extracted, dried for 60 min and then replanted after root treatment. The rats were divided into four groups (control, alendronate, etidronate, zoledronate) as following treatments of avulsed root before replantation. At 7, 14, and 28 days postreplantation, the animals were sacrificed and the samples obtained and process for microscopic analysis. The data were statistically analyzed with the SPSS procedure, anova test and each test was complemented by the Tukey’s post hoc test. The result indicated that topical application of alendronate and zoledronate, both nitrogen containing BPs, prevented inflammatory root resorption and inflammatory cell response in the delayed replantation model. Both drugs were demonstrated similar effects in the delayed tooth replantation model (P = 0.9). Etidronate did not prevent inflammatory root resorption and inflammation in the delayed replantation (P < 0.05). No significant differences in replacement root resorption were observed among all drugs. These results suggest that when teeth are dried and not replanted immediately, zoledronate, like alendronate, may prevent root resorption and facilitates the regeneration of periodontal tissues after replantation.
Effective treatment of self‐injurious oral trauma in Lesch–Nyhan syndrome: a case report
Authors: Arhakis Aristidis , Topouzelis Nikolaos , Kotsiomiti Eleni , Kotsanos Nikolaos
Published: November 2010

Abstract –  Lesch–Nyhan syndrome (LNS) is an X‐linked disorder originating from deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase. It is characterized by neurological manifestations, including the dramatic symptom of compulsive self‐mutilation, which results in destruction of oral and perioral tissues. Several drug trials have been administered to improve the severe self‐destructive behaviour, with questionable effectiveness. Invasive treatment approaches, such as extraction of teeth and orthognathic surgery, have been suggested with variable success. A conservative treatment with an intraoral appliance serving to prevent oral and peri‐oral self‐injury is presented in this report. The patient was a 14‐year‐old boy demonstrating the typical LNS behaviour, including compulsive self‐biting, significant loss of lip and tongue tissue, spasticity and involuntary movements. An acrylic maxillary appliance was designed and constructed with an occlusal plate raising the bite. The appliance was retained by two Adams’ clasps on the first premolars, along with three ball clasps between the incisors. Fabrication, insertion, and maintenance were uncomplicated and non‐stressful to the patient. Periodic recall over 3‐year period has confirmed the effective healing of the oral lesions and a high level of tolerance of the appliance.
Traumatic dental injuries during anaesthesia: part I: clinical evaluation
Authors: Rosa Maria Gaudio , Paolo Feltracco , Stefania Barbieri , Letizia Tiano , Martina Alberti , Massimiliano Delantone , Carlo Ori , Maria Avato Francesco
Published: November 2010

Abstract –  Dental injuries represent the most common claims against the anaesthesiologist. Dental lesions are frequent complications of oro‐tracheal intubation and major causal factors are (i) poor dentition, (ii) aggressive laryngoscopy, (iii) insufficient anaesthesia and curarization, (iv) emergency interventions and (v) lack of experience by the anaesthesiologist. Materials and methods: We conducted a retrospective analysis of 83 cases of dental lesions occurring during elective, emergent and urgent surgery requiring general anaesthesia with tracheal tube placement in the years between 2000 and 2008. Preoperative evaluation of dental status was obtained from the anaesthesiology chart, filled by an experienced anaesthesiologist during the preoperative visit. Anaesthesiological records were inspected by physicians of Legal Medicine Department with the aim to attribute responsibility for the damage and manage potential reimbursements. Costs related to the required dental repair were also noted. Results: Eighty‐three patients of a total of 60.000 surgical procedures (no day surgery) under general anaesthesia were affected by dental lesions (0.13%). Seventy‐five per cent of lesions occurred during intubation manoeuvres for elective major surgery, 15% occurred at tracheal intubation for minor surgery and 10% were related to emergency surgery. Teeth avulsions accounted for 50% of lesions, followed by damage to crowns and bridges (14%), luxations and fractures (>15%). Discussion: The overall incidence of dental injury in our retrospective study was 1.38 per 1000 anaesthetics, which is slightly higher than those reported by some and lower with respect to others. Avulsion of a permanent tooth occurred in patients who were affected by severe mobility of native teeth while undergoing surgery. Even though the majority of anaesthesiologists were trained enough in the use of airway devices and aware of the potential damage while using excessive forces, some unexpected difficulties may have led to lesions. It is known that damage to teeth can occur even in the absence of negligence.
On the mechanisms of bananin activity against severe acute respiratory syndrome coronavirus
Authors: Wang Zai , Huang Jian‐Dong , Wong Kin‐Ling , Wang Pei‐Gang , Zhang Hao‐Jie , Tanner Julian A. , Spiga Ottavia , Bernini Andrea , Zheng Bo‐Jian , Niccolai Neri
Published: November 2010

In a previous study, severe acute respiratory syndrome coronavirus (SARS‐CoV) was cultured in the presence of bananin, an effective adamantane‐related molecule with antiviral activity. In the present study, we show that all bananin‐resistant variants exhibit mutations in helicase and membrane protein, although no evidence of bananin interference on their mutual interaction has been found. A structural analysis on protein sequence mutations found in SARS‐CoV bananin‐resistant variants was performed. The S259/L mutation of SARS‐CoV helicase is always found in all the identified bananin‐resistant variants, suggesting a primary role of this mutation site for bananin activity. From a structural analysis of SARS‐CoV predicted helicase structure, S259 is found in a hydrophilic surface pocket, far from the enzyme active sites and outside the helicase dimer interface. The S/L substitution causes a pocket volume reduction that weakens the interaction between bananin and SARS‐CoV mutated helicase, suggesting a possible mechanism for bananin antiviral activity.
Education and growth: A simple model with complicated dynamics
Authors: Palivos Theodore , Varvarigos Dimitrios
Published: November 2010

We construct a simple model of education and growth in which children spend a fraction of their time and parents spend a fraction of their income on education. Both a strategic complementarity and an intergenerational externality are present. The interactions between each pair of consecutive generations lead to rich dynamics. We show that multiple growth equilibria arise, some of them periodic and some aperiodic. We also find a negative correlation between volatility and growth, without a one‐way causal relationship between the two being, necessarily, present. Rather, this negative correlation is driven by the structural characteristics of the economy.
Reasonable Grounds Evidence Involving Sexual Violence in Darfur
Authors: Hagan John , Brooks Richard , Haugh Todd
Published: November 2010

Internal and international conflicts can often involve a level of impunity that allows sexual violence to persist unchecked by military and political leaders. The recent reversal by an appeals panel at the International Criminal Court of a pretrial decision not to charge President al‐Bashir of Sudan with genocide in Darfur offers an important foundation for introducing new types of evidence that can increase the investigation and prosecution of sexual violence during conflicts. The reversal cited the incorrect use of the “beyond a reasonable doubt” standard when the lesser standard of “reasonable grounds” applied. Social science provides methods and measures that can be uniquely used to develop reasonable grounds evidence, for example, to demonstrate the roles of physical perpetrators acting together in horizontal relationships, as well as to establish the indirect participation through vertical relationships of higher‐level defendants, in a chain of command of superior responsibility. We illustrate these points by presenting social science evidence of the responsibility of President al‐Bashir and middle‐ and lower‐level figures in genocidal violence in Darfur.
Law's Allure and the Power of Path‐Dependent Legal Ideas
Authors: Epp Charles R.
Published: November 2010

Gordon Silverstein'sLaw's Allure(2009) advances a two‐part thesis on the power of legal ideas. The first is that legal precedents establish the ideological baselines on which legislative and bureaucratic policies are developed. Silverstein amply demonstrates the validity of this thesis. The second is that by establishing ideological baselines, legal precedents contribute to a version of path dependency (or the idea that early choices determine long‐term developments) that is significantly more constraining than other forms of institutional entrenchment. Put simply, law shackles creativity in politics. This thesis I do not find persuasive, in part because Silverstein offers little evidence for it and in part because a growing body of literature suggests the contrary: the cross‐fertilization of ideas from one field to another—law to politics, for instance—contributes to, rather than retards, creative change. Nonetheless, while its broader ambitions are not satisfied,Law's Allure's narrow thesis—that precedent profoundly shapes policy development—is important and worthy of a major book in itself.
Silverstein's Allure
Authors: Melnick R. Shep
Published: November 2010

Using multiple case studies, Gordon Silverstein's
Law's Allure (2009) examines the many ways in which courts interact with other governing institutions. He convincingly argues that legal advocates fare best when they use the leverage created by courtroom victories to increase their influence in other arenas, particularly legislatures. His more ambitious effort to explain when court intervention improves rather than displaces politics is less successful. He favors using court decisions as battering rams to break through the institutional barriers created by our allegedly outmoded Constitution. Such an open‐ended justification for judicial policy making places virtually no limits on the juridification that Silverstein decries for distorting democratic politics.
Distributive Justice through Tort (and Why Sociolegal Scholars Should Care)
Authors: Bernstein Anita
Published: November 2010

Drawing on two books central to an emerging sociolegal literature about tort—Fault Lines: Tort Law as Cultural Practice, a collection edited by David M. Engel and Michael McCann, and Torts, Egalitarianism and Distributive Justice, a monograph by Tsachi Keren‐Paz—this essay argues that tort law in the United States redistributes wealth in ways that ought to trouble sociolegal scholars and enlist their reformist energy. Read together, the two volumes offer considerable description and critique of a distributive injustice, and lead to important proposals for change.
Hot Money and Business Cycle Volatility: Evidence from China
Authors: Guo Feng , Huang Ying
Published: November 2010

This paper investigates the link between hot money and business cycle volatility in China from January 1997 to December 2009. Using the structural vector error correction model, we find a considerable degree of long‐run cointegration and bidirectional causality effects between hot money and business cycle volatility. The speculative shocks are found to temporarily promote China's economic growth, but also to exacerbate business cycle volatility. The liquidity shock stemming from hot money is shown to be the primary factor responsible for the significantly enhanced fluctuation in business cycles during the most recent global financial crisis period. This could be detrimental to the smooth operation of financial markets. Therefore, in forming future policies, it is critical for policy‐makers to take precautions against the speculative factors.
The Tripartite Model in Childhood and Adolescence: Future Directions for Developmental Research
Authors: De Bolle Marleen , De Fruyt Filip
Published: November 2010

Abstract— The tripartite model proposed by L. A. Clark and D. Watson (1991) describes the common and unique features of anxiety and depression by delineating their relation with the dimensions of negative affect, positive affect, and physiological hyperarousal. Although this model was initially developed for adults, researchers have been increasingly interested in its applicability to a younger age range. However, several problems have hindered meaningful systematic research and forestalled conclusions regarding the validity of the model in childhood and adolescence. This article provides a review of these difficulties, along with a number of recommendations for future research, in order to enhance a firm understanding of the development of the tripartite dimensions, their interrelations, and their relations to anxiety, depression, and other Axis I disorders across the life span.
Toward an Externalizing Spectrum in DSM–V: Incorporating Developmental Concerns
Authors: Tackett Jennifer L.
Published: November 2010

Abstract— Progress and innovation in DSM–V include the proposal of a new structural organization of disorders that stands to bring childhood and adult disorders together. Specifically, many common disorders would be grouped under broader dimensions of internalizing and externalizing problems. Although this distinction originated in childhood psychopathology research, current work has drawn heavily from studies with adults. The integration of common childhood disorders into the current approach remains an important task. This article reviews evidence for a structural model of externalizing pathology with a focus on research with younger populations and highlights both commonalities and distinctions that exist between externalizing dimensions in children and the externalizing spectrum in adults. The article also summarizes 3 areas that pose key questions for delineating an externalizing spectrum that better reflects developmental concerns: the incorporation of childhood disorders, the integration of temperament and personality traits, and better accounting for relevant developmental issues, including person–environment interaction, critical developmental periods, and differentiating normal and abnormal behavior.
Evidence for “Rose‐Colored Glasses”: An Examination of the Positivity Bias in Young Children’s Personality Judgments
Authors: Boseovski Janet J.
Published: November 2010

Abstract—Young children exhibit a positivity bias in their judgment of personality traits, wherein they attend to or process information selectively to maintain optimistic views of the self and others. In addition to its theoretical relevance for developing a cohesive model of personality reasoning, the positivity bias has implications for several aspects of psychosocial well‐being (e.g., peer relations, personal safety). Despite its importance and recurrence across many research studies, little attention has been devoted to studying the positivity bias systematically. This article describes 3 lines of research that demonstrate a positivity bias in early personality reasoning and presents arguments for the role of adaptive immaturity and socialization factors in setting the stage for, and perpetuating, the positivity bias. Suggestions for future research center on the need to consider the positivity bias as a profile of personality attribution, to identify the factors that contribute to the bias, and to understand the significance of the bias over the course of development.
Empirical Evaluation of a Simple Analytical Formula for the Ultraviolet Index
Authors: Antón Manuel , Serrano Antonio , Cancillo María Luísa , García José Agustín , Madronich Sasha
Published: November 2010

This paper focuses on the estimation of the UV Index (UVI) for all sky conditions using a simple analytical parameterization involving three independent variables: the solar zenith angle, the total ozone column and the clearness index. Measurements of the UVI made at Badajoz and Cáceres (Southwestern Spain) from January 2006 to December 2007 are used to estimate optimal fitting parameters for the model formula, while measurements from January to December 2008 are used to show that the formula‐based estimations have mean absolute errors lower than 6% and R2ca 0.99.
Advancement in carbon nanotubes: basics, biomedical applications and toxicity
Authors: Beg Sarwar , Rizwan Mohammad , Sheikh Asif M , Hasnain M Saquib , Anwer Khalid , Kohli Kanchan
Published: November 2010

Objectives

Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites.

Key findings

CNTs have been employed in the development of molecular electronic, composite materials and others due to their unique atomic structure, high surface area-to-volume ratio and excellent electronic, mechanical and thermal properties. Recently they have been exploited as novel nanocarriers in drug delivery systems and biomedical applications. Their larger inner volume as compared with the dimensions of the tube and easy immobilization of their outer surface with biocompatible materials make CNTs a superior nanomaterial for drug delivery. Literature reveals that CNTs are versatile carriers for controlled and targeted drug delivery, especially for cancer cells, because of their cell membrane penetrability.

This review enlightens the biomedical application of CNTs with special emphasis on utilization in controlled and targeted drug delivery, as a diagnostics tool and other possible uses in therapeutic systems. The review also focuses on the toxicity aspects of CNTs, and revealed that genotoxic potential, mutagenic and carcinogenic effects of different types of CNTs must be explored and overcome by formulating safe biomaterial for drug delivery. The review also describes the regulatory aspects and clinical and market status of CNTs.
Relative similarity within purine nucleotide and ligand structures operating on nitric oxide synthetase, guanylyl cyclase and potassium (KATP, BKCa) channels
Authors: Williams W Robert
Published: November 2010

Objectives

Purine nucleotides play a central role in signal transduction events initiated at the cell membrane. The NO–cGMP–cGK pathway, in particular, mediates events involving NOS and some classes of K+ ion channel. The aim of this study is to investigate relative molecular similarity within the ligands binding to NOS, KATP, BKCa channels and regulatory nucleotides.

Methods

Minimum energy conformers of the ligand structures were superimposed and fitted to l-arginine and the nucleotides of adenine and guanine using a computational program.

Key findings

Distinctive patterns were evident in the fitting of NOS isoform antagonists to l-arginine. KATP channel openers and antagonists superimposed on the glycosidic linkage and imidazole ring of the purine nucleotides, and guanidinium and ribose groups of GTP in the case of glibenclamide. The fits of BKCa channel openers and antagonists to cGMP were characterized by the linear dimensions of their structures; distances between terminal oxy groups in respect of dexamethasone and aldosterone.

Conclusions

The findings provide structural evidence for the functional interaction between K+ channel openers/antagonists and the regulatory nucleotides. Use of the purine nucleotide template systematizes the considerable heterogeneity evident within the structures of ligands operating on K+ ion channels.
Fast-dissolving sublingual solid dispersion and cyclodextrin complex increase the absorption of perphenazine in rabbits
Authors: Turunen Elina , Mannila Janne , Laitinen Riikka , Riikonen Joakim , Lehto Vesa-Pekka , Järvinen Tomi , Ketolainen Jarkko , Järvinen Kristiina , Jarho Pekka
Published: November 2010

Objectives

The sublingual administration route as well as solid dispersion formation with macrogol 8000 and complexation with β-cyclodextrin (β-CyD) were investigated as ways for improving the absorption of perphenazine, a poorly water-soluble drug subjected to substantial first-pass metabolism.

Methods

The absorption of perphenazine was studied in rabbits after sublingual administration of perphenazine/macrogol solid dispersion, solid perphenazine/β-CyD complex and plain micronized perphenazine, as well as after peroral administration of an aqueous perphenazine solution. Solid formulations were prepared by freeze-drying (perphenazine/macrogol solid dispersion) or spray-drying (perphenazine/β-CyD complex).

Key findings

The value for area under the curve from 0 to 360 min (AUC0–360 min) of perphenazine after peroral administration was only 8% of the AUC0–360 min value obtained after intravenous administration, while the corresponding values for the sublingually administered formulations were 53% (perphenazine/macrogol solid dispersion), 41% (perphenazine/β-CyD complex) and 64% (micronized perphenazine). There are three possible mechanisms to explain these results: avoidance of the first-pass metabolism; good sublingual absorption of perphenazine; and rapid dissolution rate of perphenazine from the studied formulations.

Conclusions

With sublingual administration, the drug has to dissolve rapidly in a small volume of saliva. Based on the present absorption studies in rabbits, the solid dispersion preparation and cyclodextrin complexation were postulated to be useful ways to attain successful sublingual administration of perphenazine. Good sublingual absorption was also achieved by micronization of perphenazine. As far as we are aware, this paper is one of the first to evaluate the sublingual administration of a solid dispersion in vivo.
Investigation of the interaction of biodegradable micro- and nanoparticulate drug delivery systems with platelets
Authors: Ramtoola Zebunnissa , Lyons Pierce , Keohane Kieran , Kerrigan Steve W , Kirby Brian P , Kelly John G
Published: November 2010

Objectives

Biodegradable micro- and nanoparticles are being increasingly investigated for drug delivery and targeting of therapeutics. The size and surface properties of these particles are important factors influencing their interaction and uptake by various cells, tissues and organs. Optimising these properties, to enhance cellular uptake, may increase their potential for interaction with other physiological components such as platelets resulting in platelet activation and inappropriate thrombus formation. The aim of this study was to investigate the potential interaction of particulates with platelets.

Methods

Biodegradable micro- and nanoparticles based on poly-lactide-co-glycolide (PLGA), poly-lactide-co-glycolide–macrogol (PLGA-macrogol) and chitosan were prepared using solvent evaporation, spray drying or solvent dispersion techniques.

Key findings

Microparticles formulated had a median diameter (D50%) of 2–9 µm, while nanoparticles had an average diameter of 100–500 nm. The surface morphology ranged from smooth and spherical to irregular depending on polymer and preparation method used. Particles, reconstituted in the concentration range of 0.1–500 µg/ml, were tested for their ability to induce or inhibit platelet aggregation. No effects on either induction of platelet activity or inhibition of aggregation were detected.

Conclusions

None of the particles examined were found to alter platelet activity. These results suggested that the biodegradable micro- and nanoparticles tested were safe for use as potential drug carriers of therapeutic agents.
Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of liquiritigenin and its two glucuronides, M1 and M2, in rats
Authors: Kang Hee E , Sohn Se I , Baek Seung R , Lee Jee W , Lee Myung G
Published: November 2010

Objectives

Liver disease and acute renal failure (ARF) are closely associated. The pharmacokinetics of liquiritigenin (LQ), a candidate therapy for inflammatory liver disease, and its metabolites M1 and M2 were evaluated in rats with ARF induced by uranyl nitrate (U-ARF rats).

Methods

LQ was administered intravenously (20 mg/kg) or orally (50 mg/kg) in U-ARF and control rats, and uridine diphosphate-glucuronosyltransferases (UGT) activity and uridine 5′-diphosphoglucuronic acid (UDPGA) concentrations were determined in the liver and intestine.

Key findings

After intravenous LQ administration, U-ARF rats displayed significantly slower LQ renal clearance but no significant changes in the LQ area under the plasma concentration–time curve (AUC) compared with controls. This was because of similar hepatic UGT activity and UDPGA levels between two groups, which resulted in comparable non-renal clearance, as well as the limited contribution of LQ renal clearance to total LQ clearance. However, the AUC and AUCM/AUCLQ ratios of M1 and M2 were significantly increased in U-ARF rats because of decreased urinary excretion of M1 and M2. Similar results were observed following oral administration because of the comparable LQ intestinal metabolism in both groups and decreased urinary excretion of M1 and M2 in U-ARF rats.

Conclusions

U-ARF rats displayed decreased urinary excretion of LQ glucuronides, resulting in significantly greater AUC and metabolite ratios of M1 and M2 following LQ administration.
Regulation of erythropoietin production
Authors: Jelkmann Wolfgang
Published: November 2010

The hormone erythropoietin (Epo) maintains red blood cell mass by promoting the survival, proliferation and differentiation of erythrocytic progenitors. Circulating Epo originates mainly from fibroblasts in the renal cortex. Epo production is controlled at the transcriptional level. Hypoxia attenuates the inhibition of the Epo promoter by GATA‐2. More importantly, hypoxia promotes the availability of heterodimeric (α/β) hypoxia‐inducible transcription factors (predominantly HIF‐2) which stimulate the Epo enhancer. The HIFs are inactivated in normoxia by enzymatic hydroxylation of their α‐subunits. Three HIF‐α prolyl hydroxylases (PHD‐1, ‐2 and ‐3) initiate proteasomal degradation of HIF‐α, while an asparaginyl hydroxylase (‘factor inhibiting HIF‐1’, FIH‐1) inhibits the transactivation potential. The HIF‐α hydroxylases contain Fe2+ and require 2‐oxoglutarate as co‐factor. The in vivo response is dynamic, i.e. the concentration of circulating Epo increases initially greatly following an anaemic or hypoxaemic stimulus and then declines despite continued hypoxia. Epo and angiotensin II collaborate in the maintenance of the blood volume. Whether extra‐renal sites (brain, skin) modulate renal Epo production is a matter of debate. Epo overproduction results in erythrocytosis. Epo deficiency is the primary cause of the anaemia in chronic kidney disease and a contributing factor in the anaemias of chronic inflammation and cancer. Here, recombinant analogues can substitute for the hormone.
Effect of P2 receptor blockade with pyridoxine on sympathetic response to exercise pressor reflex in humans
Authors: Cui Jian , Leuenberger Urs A. , Blaha Cheryl , King Nicholas C. , Sinoway Lawrence I.
Published: November 2010

Non‐technical summary

During exercise, sympathetic nervous system activity increases and this contributes to an increase in blood pressure (i.e. exercise pressor reflex). Although animal studies suggest that purinergic P2 receptors on thin fibre sensory nerves are stimulated and evoke this reflex, human data are lacking. In this study, young healthy volunteers performed fatiguing isometric handgrip before and after a local infusion of pyridoxine (i.e. vitamin B6) into the ‘isolated’ circulation of the human forearm. Pyridoxine is converted into a P2‐purinoceptor antagonist. Muscle sympathetic nerve activity and blood pressure responses to fatiguing handgrip and post‐exercise circulatory occlusion were significantly less after pyridoxine than they were before. These effects were not observed after infusion of saline. These data suggest that P2 receptors contribute to the exercise pressor reflex in humans.
Testosterone restores respiratory long term facilitation in old male rats by an aromatase‐dependent mechanism
Authors: Nelson N. R. , Bird I. M. , Behan M.
Published: November 2010

Non‐technical summary

Steroidal sex hormones (testosterone, oestradiol and progesterone) play an important role in the neural control of breathing. Hormone levels typically change throughout life. Testosterone levels increase during puberty in boys, but from ∼30 years of age levels decline gradually. The typical age of onset for obstructive sleep apnoea, a prominent breathing disorder of older humans, is ∼50 years of age in men. In a study in old male rats, we show that testosterone supplementation can reverse the age‐associated decrease in one measurement of the neural control of breathing. We conclude that testosterone supplementation can potentially be used to enhance upper airway function in the elderly.
Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren‐2 transgenic rats with inducible hypertension
Authors: Honetschlägerová Zuzana , Husková Zuzana , Vaňourková Zdeňka , Sporková Alexandra , Kramer Herbert J. , Hwang Sung Hee , Tsai Hsing‐Ju , Hammock Bruce D. , Imig John D. , Červenka Luděk , Kopkan Libor
Published: November 2010

Non‐technical summary

Arachidonic acid metabolites called epoxyeicosatrienoic acids (EETs) influence vascular tone and renal tubular sodium and water transport and thus have been implicated in the control of blood pressure. Inhibition of the enzyme soluble epoxide hydrolase (sEH), which reduces EET degradation to the corresponding diols, leads to substantial attenuation of malignant hypertension in a transgenic rat strain harbouring the mouse renin gene particularly via an improvement of renal function. The observed antihypertensive and renoprotective effects of this novel pharmacological approach provide a potentially new direction in antihypertensive therapy.
Unperturbed islet α‐cell function examined in mouse pancreas tissue slices
Authors: Huang Ya‐Chi , Rupnik Marjan , Gaisano Herbert Y.
Published: November 2010

Non‐technical summary

Critical investigation into pancreatic islet α‐cell biology in health and diabetes has been sparse and inconsistent because of technical difficulties in islet isolation and dispersion into single cells. We have circumvented these difficulties by employing the pancreas slice preparation. We functionally characterized (electrophysiologically) the α‐cells in their in situ native state, then loaded the tested cells with biocytin dye to subsequently confirm the cell identities by immunocytochemistry. We characterized a very large number of α‐cells, which showed a wide‐range distribution in the electrophysiological parameters of several ion channels (ATP‐sensitive K+, Na+ and Ca2+ currents) and capacitance changes as measure of exocytosis of glucagon granules. This could explain the apparent inconsistency of previous reports on α‐cells that inadvertently showed skewed data due to insufficient sampling of α‐cells. Our innovative approaches will enable future studies into elucidating α‐cell dysregulation in diabetes.
Role of blood flow in carotid body chemoreflex function in heart failure
Authors: Ding Yanfeng , Li Yu‐Long , Schultz Harold D.
Published: November 2010

Non‐technical summary

Activation of the sympathetic nervous system hastens the rate of progression and severity of chronic heart failure (CHF). Chemically sensitive nerves in the carotid body (CB) that stimulate sympathetic nerve activity become overly active in CHF and contribute to this phenomenon. The stimulus for activation of these CB chemoreceptors is not known. Blood supply to tissues is impaired due to the failing heart. In this study we tested whether a chronic reduction in blood flow to the CB may contribute to altered CB chemoreceptor function. The results show that changes that occur in CB chemoreceptor function during CHF are identical to those that occur if blood flow is simply reduced to the CB for several weeks. The results suggest that chronic impairment of blood flow may be the key step in the pathophysiological events that cause sympathetic nervous system activation in heart failure.
Characteristics of Pool Boiling Bubble Dynamics in Bead Packed Porous Structures
Authors: Li Calvin H. , Li Ting , Hodgins Paul , Peterson G. P.
Published: November 2010

Spherical glass and copper beads have been used to create bead packed porous structures for an investigation of two-phase heat transfer bubble dynamics under geometric constraints. The results demonstrated a variety of bubble dynamics characteristics under a range of heating conditions. The bubble generation, growth, and detachment during the nucleate pool boiling heat transfer have been filmed, the heating surface temperatures and heat flux were recorded, and theoretical models have been employed to study bubble dynamic characteristics. Computer simulation results were combined with experimental observations to clarify the details of the vapor bubble growth process and the liquid water replenishing the inside of the porous structures. This investigation has clearly shown, with both experimental and computer simulation evidence, that the millimeter scale bead packed porous structures could greatly influence pool boiling heat transfer by forcing a single bubble to depart at a smaller size, as compared with that in a plain surface situation at low heat flux situations, and could trigger the earlier occurrence of critical heat flux by trapping the vapor into interstitial space and forming a vapor column net at high heat flux situations. The results also proved data for further development of theoretical models of pool boiling heat transfer in bead packed porous structures.
Lubricant-Derived Ash Properties and Their Effects on Diesel Particulate Filter Pressure-Drop Performance
Authors: Sappok Alexander , Wong Victor W.
Published: November 2010

Diesel particulate filters (DPFs) have seen widespread use in on- and off-road applications as an effective means for meeting increasingly stringent particle emission regulations. Over time, incombustible material or ash, primarily derived from metallic additives in the engine lubricant, accumulates in the DPF. Ash accumulation leads to increased flow restriction and an associated increase in pressure-drop across the particulate filter, negatively impacting engine performance and fuel economy and eventually requiring periodic filter service or replacement. While the adverse effects of ash accumulation on DPF performance are well known, the underlying mechanisms controlling these effects are not. The results of this work show ash accumulation and distribution in the DPF as a dynamic process with each stage of ash accumulation altering the filter’s pressure-drop response. Through a combined approach employing targeted experiments and comparison with the existing knowledge base, this work further demonstrates the significant effect ash deposits have on DPF pressure-drop sensitivity to soot accumulation. Ash deposits reduce the available filtration area, resulting in locally elevated soot loads and higher exhaust gas velocities through the filter, altering the conditions under which the soot is deposited and ultimately controlling the filter’s pressure-drop characteristics. In this study, a novel accelerated ash loading system was employed to generate the ash and load the DPFs under carefully controlled exhaust conditions. The ash loading system was coupled to the exhaust of a Cummins ISB diesel engine, allowing for accelerated ash loading and DPF performance evaluation with realistic exhaust conditions. Following DPF performance evaluation, the filters were subjected to a detailed post-mortem analysis in which key ash properties were measured and quantified. The experimental results, coupled with the ash property measurements, provide additional insight into the underlying physical mechanisms controlling ash properties, ash/soot interactions, and their effects on DPF performance.
Modeling Wall Film Formation and Breakup Using an Integrated Interface-Tracking/Discrete-Phase Approach
Authors: Arienti M. , Wang L. , Corn M. , Li X. , Soteriou M. C. , Shedd T. A. , Herrmann M.
Published: November 2010

We propose a computationally tractable model for film formation and breakup based on data from experiments and direct numerical simulations. This work is a natural continuation of previous studies where primary atomization was modeled based on local flow information from a relatively low-resolution tracking of the liquid interface [Arienti and Soteriou, 2007, “Dynamics of Pulsed Jet in Crossflow,” ASME Paper No. GT2007-27816]. The submodels for film formation proposed here are supported by direct numerical simulations obtained with the refined level set grid method [Herrmann, 2008, “A Balanced Force Refined Level Set Grid Method for Two-Phase Flows on Unstructured Flow Solver Grids,” J. Comput. Phys., 227, pp. 2674–2706]. The overall approach is validated by a carefully designed experiment [Shedd et. al., 2009, “Liquid Jet Breakup by an Impinging Air Jet,” Forty-Seventh AIAA Aerospace Sciences Meeting. Paper No. AIAA-2009-0998], where the liquid jet is crossflow-atomized in a rectangular channel so that a film forms on the wall opposite to the injection orifice. The film eventually breaks up at the downstream exit of the channel. Comparisons with phase Doppler particle analyzer data and with nonintrusive film thickness point measurements complete this study.
Performance Model “Zooming” for In-Depth Component Fault Diagnosis
Authors: Aretakis N. , Roumeliotis I. , Mathioudakis K.
Published: November 2010

A method giving the possibility for a more detailed gas path component fault diagnosis by exploiting the “zooming” feature of current performance modeling techniques is presented. A diagnostic engine performance model is the main tool that points to the faulty engine component. A diagnostic component model is then used to identify the fault. The method is demonstrated on the case of compressor faults. A 1D model based on the “stage stacking” approach is used to “zoom” into the compressors, supporting a 0D engine model. A first level diagnosis determines the deviation of overall compressor performance parameters while zooming calculations allow a localization of the faulty stages of a multistage compressor. The possibility to derive more detailed information with no additional measurement data is established by the incorporation of empirical knowledge on the type of faults that are usually encountered in practice. Although the approach is based on known individual diagnostic methods, it is demonstrated that the integrated formulation provides not only higher effectiveness but also additional fault identification capabilities.
An Immersed Particle Heat Exchanger for Externally Fired and Heat Recovery Gas Turbines
Authors: Catalano Luciano Andrea , De Bellis Fabio , Amirante Riccardo , Rignanese Matteo
Published: November 2010

Designing and manufacturing high-efficiency heat exchangers is usually considered a limiting factor in the development of gas turbines employing either heat recovery Joule–Brayton cycles or external combustion. In this work, an innovative heat exchanger is proposed, modeled, and partially tested to validate the developed numerical model employed for its design. The heat exchanger is based on an intermediate medium (aluminum oxide Al2O3) flowing in countercurrent through an hot stream of gas. In this process, heat can be absorbed from the hot gas, temporarily stored, and then similarly released in a second pipe, where a cold stream is warmed up. A flow of alumina particles with very small diameter (of the order of hundreds of microns) can be employed to enhance the heat transfer. Experimental tests demonstrate that simple one-dimensional steady equations, also neglecting conduction in the particles, can be effectively employed to simulate the flow in the vertical part of the pipe, namely, to compute the pipe length required to achieve a prescribed heat exchange. On the other side, full three-dimensional computational fluid dynamics simulations have been performed to demonstrate that a more thorough gas flow and particle displacement analysis is needed to avoid a bad distribution of alumina particles and, thus, to achieve high thermal efficiency.
Thermal Science of Weld Bead Defects: A Review
Authors: Wei P. S.
Published: November 2010

Mechanisms for the formation of bead defects, such as humping, gouging, rippling, and other unexpected surface patterns, encountered in welding or drilling are interpreted and reviewed from thermal-fluid science viewpoint. These defects usually accompanying with porosity, undercut, segregation, stress concentration, etc., seriously reduce the properties and strength of the joint or solidification. Even though different mechanisms for formation of the defects have been extensively proposed in the past, more systematical understanding of pattern formations from thermal, fluid, physics, electromagnetic, pattern selections, and metallurgy sciences is still limited. The effects of working parameters and properties on humping and rippling, for example, can be systematically and quantitatively interpreted from scale analysis presented in this work. Good comparison with experimental results reveals mechanisms of different surface patterns. The mechanistic findings for bead defects are also useful for other manufacturing and materials processing.