bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the cGMP/PKG pathway inhibits electrical activity in rabbit urethral interstitial cells of Cajal by reducing the spatial spread of Ca2+waves
Authors: Sergeant G. P. , Johnston Louise , McHale N. G. , Thornbury K. D. , Hollywood M. A.
Published: April 2006

In the present study we used a combination of patch clamping and fast confocal Ca2+imaging to examine the effects of activators of the nitric oxide (NO)/cGMP pathway on pacemaker activity in freshly dispersed ICC from the rabbit urethra, using the amphotericin B perforated patch configuration of the patch‐clamp technique. The nitric oxide donor, DEA‐NO, the soluble guanylyl cyclase activator YC‐1 and the membrane‐permeant analogue of cGMP, 8‐Br‐cGMP inhibited spontaneous transient depolarizations (STDs) and spontaneous transient inward currents (STICs) recorded under current‐clamp and voltage‐clamp conditions, respectively. Caffeine‐evoked Cl−currents were unaltered in the presence of SP‐8‐Br‐PET‐cGMPs, suggesting that activation of the cGMP/PKG pathway does not block Cl−channels directly or interfere with Ca2+release via ryanodine receptors (RyR). However, noradrenaline‐evoked Cl−currents were attenuated by SP‐8‐Br‐PET‐cGMPs, suggesting that activation of cGMP‐dependent protein kinase (PKG) may modulate release of Ca2+via IP3receptors (IP3R).When urethral interstitial cells (ICC) were loaded with Fluo4‐AM (2 μm), and viewed with a confocal microscope, they fired regular propagating Ca2+waves, which originated in one or more regions of the cell. Application of DEA‐NO or other activators of the cGMP/PKG pathway did not significantly affect the oscillation frequency of these cells, but did significantly reduce their spatial spread. These effects were mimicked by the IP3R blocker, 2‐APB (100 μm). These data suggest that NO donors and activators of the cGMP pathway inhibit electrical activity of urethral ICC by reducing the spatial spread of Ca2+waves, rather than decreasing wave frequency.
Lamin A-Dependent Nuclear Defects in Human Aging
Authors: Scaffidi Paola , Misteli Tom
Published: April 2006

Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.
Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice
Authors: Twomey P J , Viljoen A , House I M , Reynolds T M , Wierzbicki A S
Published: April 2006

Background:An investigation on copper metabolism usually includes the measurement of serum levels of copper and caeruloplasmin. Using these levels, some laboratories derive levels of non-caeruloplasmin-bound copper (NCC); however, a considerable number of patients may show negative values, which is not physiologically possible.

Aim:To derive an equation for adjusted copper in a manner similar to that widely accepted for adjusted calcium.

Methods:A linear regression equation for the relationship between caeruloplasmin and copper was used: [copper] (μmol/l) = 0.052×[caeruloplasmin] (mg/l). An equation for copper adjusted for caeruloplasmin was derived using this equation and the reference interval of 10–25 μmol/l for copper.

Results:The derived equation was [adjusted copper] (μmol/l) = [total copper] (μmol/l)+0.052×[caeruloplasmin] (mg/l)+17.5 (μmol/l). The adjusted copper concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 μmol/l, respectively, with the population having a gaussian distribution. The relationship between NCC and the adjusted copper concentrations is linear and independent of caeruloplasmin concentration.

Conclusion:Calculation of copper adjusted for caeruloplasmin uses the same variables as those for NCC. Accordingly, the problems that are caused by the lack of specificity of caeruloplasmin immunoassays are the same as those identified for NCC. This calculation, however, overcomes the negative values that are found in a considerable minority of patients with NCC, as well as age and sex differences in the caeruloplasmin reference interval. As the concept is already familiar to non-laboratory healthcare professionals in the form of calcium adjusted for albumin, this method is potentially less confusing than that for NCC.
Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected withHelicobacter pylori
Authors: Derakhshan M H , El-Omar E , Oien K , Gillen D , Fyfe V , Crabtree J E , McColl K E L
Published: April 2006

Background:Acid secretion is intimately associated with most upper gastrointestinal diseases.Helicobacter pyloriinfection is a major environmental factor modifying acid secretion.

Aim:To study the association between the pattern ofH pylorigastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease.

Methods and materials:Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy andH pyloriinfection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO.

Results:Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, bodyH pyloridensity:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. TheH pyloridensity: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R2 = 0.62).

Conclusion:Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected withH pylori.
Best practice in primary care pathology: review 5
Authors: Smellie W S A , Forth J , Ryder S , Galloway M J , Wood A C , Watson I D
Published: April 2006

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question–answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.
Women’s reproductive autonomy: medicalisation and beyond
Authors: Purdy L
Published: April 2006

Reproductive autonomy is central to women’s welfare both because childbearing takes place in women’s bodies and because they are generally expected to take primary responsibility for child rearing. In 2005, the factors that influence their autonomy most strongly are poverty and belief systems that devalue such autonomy. Unfortunately, such autonomy is a low priority for most societies, or is anathema to their belief systems altogether. This situation is doubly sad because women’s reproductive autonomy is intrinsically valuable for women and also instrumentally valuable for the welfare of humankind. This paper takes for granted the moral and practical necessity of such autonomy and digs deeper into the question of what such a commitment might entail, focusing on the mid-level policy making that, at least in the US and Canada, plays a significant role in shaping women’s options. This paper examines a large teaching hospital’s policy on reduction of multifetal pregnancies. The policy permits reduction of triplets to twins, but not twins to a singleton. As there is no morally relevant difference between these two types of reduction, it is evident that inappropriate medicalisation can still limit women’s autonomy in undesirable ways.
Boundaries, borders, and limits. A phenomenological reflection on ethics and euthanasia: Figure 1
Authors: Leget C
Published: April 2006

The subject of euthanasia divides both people and nations. It will always continue to do so because the arguments for and against this issue are intrinsically related to each other. This paper offers an analysis of the interrelation of the arguments, departing from a phenomenology of boundaries. From the participant perspective the boundary of euthanasia appears as a limit. From a helicopter perspective it appears as a border. Reflecting on both perspectives they turn out to complement each other: the positive effects of the former correspond to the negative effects of the latter. In order to see how this interrelation of viewpoints works out in the case of euthanasia a paradigmatic case is analysed from the perspective of the patient, the doctor, and the family. This phenomenological analysis does not directly lead to normative conclusions. It helps by both paying attention to, and dealing with, the complexity of the issue with intellectual honesty.
Long term health complaints following the Amsterdam Air Disaster in police officers and fire-fighters
Authors: Huizink A C , Slottje P , Witteveen A B , Bijlsma J A , Twisk J W R , Smidt N , Bramsen I , van Mechelen W , van der Ploeg H M , Bouter L M , Smid T
Published: April 2006

Background:On 4 October 1992, a cargo aircraft crashed into apartment buildings in Amsterdam, the Netherlands. Fire-fighters and police officers assisted with the rescue work.

Objectives:To examine the long term health complaints in rescue workers exposed to a disaster.

Methods:A historical cohort study was performed among police officers (n = 834) and fire-fighters (n = 334) who performed at least one disaster related task and reference groups of their non-exposed colleagues (n = 634 and n = 194, respectively). The main outcome measures included digestive, cardiovascular, musculoskeletal, nervous system, airway, skin, post-traumatic stress, fatigue, and general mental health complaints; haematological and biochemical laboratory values; and urinalysis outcomes.

Results:Police officers and fire-fighters who were professionally exposed to a disaster reported more physical and mental health complaints, compared to the reference groups. No clinically relevant statistically significant differences in laboratory outcomes were found.

Conclusions:This study is the first to examine long term health complaints in a large sample of rescue workers exposed to a disaster in comparison to reference groups of non-exposed colleagues. Findings show that even in the long term, and in the absence of laboratory abnormalities, rescue workers report more health complaints.
PIEZONUCLEAR REACTIONS AND LORENTZ INVARIANCE BREAKDOWN
Authors: CARDONE F. , MIGNANI R.
Published: April 2006

In the last years experiments of cavitating water and of explosions of foils in water have provided possible evidence for production of stable, unstable and artificial nuclides induced by ultrasounds and shock waves, i.e. for nuclear reactions induced by pressure waves (piezonuclear reactions). We propose a possible mechanism for the explanation of these findings, that is constituted by two parts: a classical one, based on the bubble implosion due to cavitation, and a non-classical, related to a possible breakdown of Lorentz invariance for nuclear interactions. Such a mechanism allows one to get precise predictions on the values of energy and power needed to carry out experiments with the commercially available sonotrodes and to get piezonuclear reactions in a reproducible way.
FUEL BURNUP AND FUEL POOL SHIELDING ANALYSIS FOR BUSHEHR NUCLEAR REACTOR VVER-1000
Authors: HADAD KAMAL , AYOBIAN NAVID
Published: April 2006

Bushehr Nuclear power plant (BNPP) is currently under construction. The VVER-1000 reactor will be loaded with 126 tons of about 4% enriched fuel having 3-years life cycle. The spent fuel (SF) will be transferred into the spent fuel pool (SPF), where it stays for 8 years before being transferred to Russia. The SPF plays a crucial role during 8 years when the SP resides in there. This paper investigates the shielding of this structure as it is designed to shield the SF radiation. In this study, the SF isotope inventory, for different cycles and with different burnups, was calculated using WIMS/4D transport code. Using MCNP4C nuclear code, the intensity of γ rays was obtained in different layers of SFP shields. These layers include the water above fuel assemblies (FA) in pool, concrete wall of the pool and water laid above transferring fuels. Results show that γ rays leakage from the shield in the mentioned layers are in agreement with the plant's PSAR data. Finally we analyzed an accident were the water height above the FA in the pool drops to 47 cm. In this case it was observed that exposure dose above pool, 10 and 30 days from the accident, are still high and in the levels of 1000 and 758 R/hr.
RELATIVISTIC TRANSPORT APPROACH TO THE NUCLEAR GROUND STATE
Authors: YILDIRIM SERBULENT
Published: April 2006

The ground state properties of finite nuclei are studied in the framework of a relativistic transport approach. The kinetic equations are derived within an effective nucleon-meson field theory in the Relativistic Mean Field (RMF) scheme. The time evolution of the binding energies and the nuclear radii are obtained for spherical nuclei with various sets of Lagrangian parameters and compared with those of Relativistic RPA results for 208 Pb . The comparison shows reasonably well results.
A GENETIC ALGORITHM APPROACH FOR MACHINE CELL FORMATION
Authors: RAJAGOPALAN RAVISHANKAR , FONSECA DANIEL J.
Published: April 2006

Cellular Manufacturing Systems (CMS) have been the key to the success of manufacturing industries in the recent past. Machine cell design, which involves formation of machine cells and component groups, represents the most important step in the design of CMS. Even though a tremendous amount of research has been conducted in this area, the gap between theoretical research and practice is widening primarily because of the lack of consideration of key production data such as production volumes, operations sequences, machine sequence inside the cells, processing times, setup times, and machine costs during the cell design stage. This paper discuses the development of a Genetic Algorithm Model (GAM), designed to assist in the formation of manufacturing cells. The GAM aims at the minimization of the material handling and the penalty costs while considering the effects of inter-cell, intra-cell, backtracking, and machine skipping movements.
COMPARATIVE ANALYSIS OF VARIOUS METHODS OF SURFACE ROUGHNESS IN DRILLING
Authors: SANJAY C.
Published: April 2006

Drilling is one of the most common and fundamental machining processes. Since approximately 40% of all the cutting operations are drilling in industry. It is most frequently performed, material removing process and is used as a preliminary step for many operations, such as reaming, tapping and boring. Because of their importance in nearly all production operations twist drills have been the subject of numerous investigations. Surface finish quality of a machined work piece is an issue of main concern to the manufacturing industry. The aim of the present work is to identify suitable parameters for the prediction of surface roughness. Back propagation neural networks were used for detection of surface roughness. Drill diameter, cutting speed, feed, and machining time were given as inputs to the neural network structure and surface roughness was estimated. Drilling experiments with 10 mm drill size were performed at three cutting speeds and feeds. The number of neurons were selected from 1,2,3,…, 20. The learning rate was selected as 0.01 and no smoothing factor was used. The best structure of neural networks were selected based on the criteria as the minimum of summation of square with the actual value of surface roughness. For statistical analysis, it was assumed that surface roughness depends on cutting speed, feed and machining time. For the mathematical analysis inverse coefficient matrix method was used for calculating the estimated values of surface roughness. Comparative analysis has been done between the actual values and the estimated values obtained by statistical analysis, mathematical analysis and neural network structure.
Cyclic exposure to ozone alters distal airway development in infant rhesus monkeys
Authors: Fanucchi Michelle V. , Plopper Charles G. , Evans Michael J. , Hyde Dallas M. , Van Winkle Laura S. , Gershwin Laurel J. , Schelegle Edward S.
Published: April 2006

Inner city children exposed to high levels of ozone suffer from an increased prevalence of respiratory diseases. Lung development in children is a long-term process, and there is a significant period of time during development when children growing up in urban areas are exposed to oxidant air pollution. This study was designed to test whether repeating cycles of injury and repair caused by episodes of ozone exposure lead to chronic airway disease and decreased lung function by altering normal lung maturation. We evaluated postnatal lung morphogenesis and function of infant monkeys after 5 mo of episodic exposure of 0.5 parts per million ozone beginning at 1 mo of age. Nonhuman primates were chosen because their airway structure and postnatal lung development is similar to those of humans. Airway morphology and structure were evaluated at the end of the 5-mo exposure period. Compared with control infants, ozone-exposed animals had four fewer nonalveolarized airway generations, hyperplastic bronchiolar epithelium, and altered smooth muscle bundle orientation in terminal and respiratory bronchioles. These results suggest that episodic exposure to environmental ozone compromises postnatal morphogenesis of tracheobronchial airways.
Medullary lateral tegmental field neurons influence the timing and pattern of phrenic nerve activity in cats
Authors: Orer Hakan S. , Gebber Gerard L. , Barman Susan M.
Published: April 2006

In an effort to characterize the role of the medullary lateral tegmental field (LTF) in regulating respiration, we tested the effects of selective blockade of excitatory (EAA) and inhibitory amino acid (IAA) receptors in this region on phrenic nerve activity (PNA) of vagus-intact and vagotomized cats anesthetized with dial-urethane. We found distinct patterns of changes in central respiratory rate, duration of inspiratory and expiratory phases of PNA (Ti and Te, respectively), and I-burst amplitude after selective blockade of EAA and IAA receptors in the LTF. First, blockade of N-methyl-d-aspartate (NMDA) receptors significantly ( P < 0.05) decreased central respiratory rate primarily by increasing Ti but did not alter I-burst amplitude. Second, blockade of non-NMDA receptors significantly reduced I-burst amplitude without affecting central respiratory rate. Third, blockade of GABAAreceptors significantly decreased central respiratory rate by increasing Te and significantly reduced I-burst amplitude. Fourth, blockade of glycine receptors significantly decreased central respiratory rate by causing proportional increases in Ti and Te and significantly reduced I-burst amplitude. These changes in PNA were markedly different from those produced by blockade of EAA or IAA receptors in the pre-Bötzinger complex. We propose that a proper balance of excitatory and inhibitory inputs to several functionally distinct pools of LTF neurons is essential for maintaining the normal pattern of PNA in anesthetized cats.
Comparative Effects of Paclitaxel and Rapamycin on Smooth Muscle Migration and Survival
Authors: Patterson Cam , Mapera Sabeen , Li Hui-Hua , Madamanchi Nageswara , Hilliard Eleanor , Lineberger Rob , Herrmann Robert , Charles Peter
Published: April 2006

Objective—

Advances in stent technology have enabled the delivery of drugs to improve outcomes after stent deployment. However, the optimal payloads for stents are not clear, and the appropriate stent-based therapies for high-risk patients, such as diabetics, have not been clearly established.

Methods and Results—

We used smooth muscle cell culture models to compare the activities of rapamycin and paclitaxel. Smooth muscle cells were grown in normal or high glucose to induce insulin resistance. Both paclitaxel and rapamycin activate mitogen-activated protein kinase pathways similarly. However, rapamycin potently activates AKT-dependent signaling, an effect that overrides the downregulation of this pathway by insulin resistance and that causes phosphorylation of the AKT-dependent transcription factor FOXO1. This effect is associated with attenuation of the anti-migratory effects of rapamycin under high glucose conditions that are not observed with paclitaxel, as well as with increased protection against ceramide-induced cytotoxicity, both of which are dependent on FOXO1 phosphorylation.

Conclusions—

Differences between the ability of rapamycin and paclitaxel to activate AKT may account for their differential cell survival and antichemotactic activities. These observations may provide a basis for understanding clinical differences between rapamycin- and paclitaxel-coated stents. The approaches used in these studies can be expanded to other candidate stent payloads as a method for triage in preclinical studies.
What are the Right Models and Policies for a World of Low Inflation?
Authors: Minford Patrick
Published: April 2006

Monetary policy should be guided by macroeconomic models with limited nominal rigidity; ‘New Classical’ or even for some issues just plain Classical (i.e. with no nominal rigidity at all) models are perfectly adequate for understanding various aspects of the economy that have previously led economists to believe in a high degree of nominal rigidity. On UK data these models account for the facts of inflation persistence and exchange rate ‘overshooting’; their impulse responses are in line with the data; and a typical example, the Liverpool Model, is marginally accepted in its entirety by the data since 1979. Such models suggest that no increased macro instability would result from taking the rigours of monetary policy one stage further from inflation targeting and ensuring that the price level itself is returned to its long-run preset target path — so that the value of money over long periods of time would be utterly predictable.
Liberal Multiculturalism
Authors: Goodin Robert E.
Published: April 2006

By analogy to Macpherson’s “protective” and “self-developmental” models of liberal democracy, there might be two distinct models of liberal multiculturalism. On the protective-style model, the aim is to protect minority cultures against assimilationist and homogenizing intrusions of the majority. On the other model, here dubbed “polyglot multiculturalism,” the majority might expand its own “context for choice” by having more minority cultures from whom to borrow. The latter is a more welcoming and inclusive strategy, still recognizably liberal in form, than the self-defensive liberalism of the more purely protectionist sort.
Resistance Can Be Good or Bad: How Theories of Resistance and Dissonance Affect Attitude Certainty
Authors: Rydell Robert J. , Hugenberg Kurt , McConnell Allen R.
Published: April 2006

This research investigated how lay theories about resisting persuasion can affect attitude certainty. Specifically, people who believed that resistance was negative (i.e., implies close-mindedness) showed different levels of attitude certainty after resisting persuasive messages than people who believed resistance was positive (i.e., implies intelligence). When people held positive lay theories of resistance and overcame ostensibly strong arguments, they showed increased attitude certainty (compared to those who overcame ostensibly weak arguments). However, individuals who believed that resistance was negative did not show increases in attitude certainty when overcoming strong arguments. Experiment 2 suggests that the effect of lay theories and perceived argument strength on attitude certainty was due to dissonance created by believing that resistance is undesirable but nonetheless resisting persuasion.
The Impact of Self-Construal on Aesthetic Preference for Angular Versus Rounded Shapes
Authors: Zhang Yinlong , Feick Lawrence , Price Lydia J.
Published: April 2006

In this article, the authors examine the role of self-construal in aesthetic preference for angular versus rounded shapes. Previous research found an independent self-construal is associated with a confrontation approach to conflict resolution, whereas an interdependent self-construal is associated with compromise. Furthermore, the literature in empirical aesthetics suggests that angular shapes tend to generate confrontational associations, and rounded shapes tend to generate compromise associations. Accordingly, the authors propose individuals with independent self-construals should perceive angular shapes as more attractive, whereas individuals with interdependent self-construals should find rounded shapes more attractive. The authors argue this effect of self-construal should be more pronounced when people expect that their shape preferences will be evaluated by others because culturally consistent responses will be more accessible in this situation. These hypotheses were largely confirmed in a field study that classified logos from a variety of countries and two experiments in which self-construal was experimentally primed.
Correlates of Subjective Stress Among Drug Court Clients
Authors: Garrity Thomas F. , Prewitt Sallie H. , Joosen Michelle , Tindall Michele Staton , Webster J. Matthew , Hiller Matthew L. , Leukefeld Carl G.
Published: April 2006

Psychosocial stress is consistently found to promote initiation, intensification, and relapse in drug abuse. It would, therefore, be desirable to identify characteristics of offenders who are at heightened risk for stress-induced exacerbations of addictive behavior. In this cross-sectional, correlational, interview study, 500 clients of two Kentucky drug courts averaged 30 years of age and were predominantly male, White, employed, high school educated, single, and adjudicated in small- and medium-size cities. Five independent correlates of greater subjective stress emerged in stepwise multiple regression analysis ( R2 = .395): use of escape-avoidance coping, positive reappraisal coping (inversely associated), more negative life events, better self-rated health (inversely associated), and access to social support related to work problems (inversely associated). Treatment interventions emphasizing effective coping styles and building of social support as well as managing of negative life events and perceptions of health may serve to lessen subjective stress and its consequences in drug-abusing criminal populations.
Talk of Class
Authors: Stuber Jenny M.
Published: April 2006

Discourses of social class are an important object of study because how people talk about social class can translate into how they act on the basis of social class. Using data from sixty in-depth interviews with white college students from working- and upper-middle-class backgrounds at two institutions of higher education, I explore college students’ social class awareness, whether they think that social class matters, and how they construct symbolic boundaries. I find that whereas there are some similarities in how working- and upper-middle-class students talk about social class, differences ultimately emerge whereby working-class respondents construct social class as a more salient issue. Moreover, in contrast to earlier research, both upper-middle- and working-class students construct symbolic boundaries vis-à-vis those above them in the stratification system. This pattern suggests some possible implications for processes of social reproduction.
The Relation of Social Isolation, Loneliness, and Social Support to Disease Outcomes Among the Elderly
Authors: Tomaka Joe , Thompson Sharon , Palacios Rebecca
Published: April 2006

Objectives: This study examined relations between social isolation, loneliness, and social support to health outcomes in a sample of New Mexico seniors. Method: We used random-digit dialing to obtain a random sample of 755 southern New Mexico seniors. Participants answered questions pertaining to demographics, social isolation and loneliness, social support, and disease diagnosis including diabetes, hypertension, heart disease, liver disease, arthritis, emphysema, tuberculosis, kidney disease, cancer, asthma, and stroke. The sample allowed for comparison of Caucasian and Hispanic participants. Results: Correlational and logistic analyses indicated that belongingness support related most consistently to health outcomes. Ethnic subgroup analysis revealed similarities and differences in the pattern of associations among the predictor and outcome variables. Discussion: The results demonstrate the importance of social variables for predicting disease outcomes in the elderly and across ethnic groups.
The Negative Association of Independent Personality and Medication Adherence
Authors: Insel Kathleen C. , Reminger Sheryl L. , Hsiao Chao-Pin
Published: April 2006

Objectives: This investigation examines the association of personality factors and medication adherence among older adults. Method: The Six-Factor Personality Questionnaire was mailed to participants involved in a medication adherence investigation. Medication adherence was monitored with an electronic monitoring cap for 8 weeks for one prescribed daily medication. Results: Sixty older adults, mean age 77 years (range 67 to 93 years), returned the questionnaire (69% response rate). Stepwise regression analysis demonstrates that when age and level of education are controlled, independence predicts medication adherence. This factor demonstrates a negative relationship with adherence suggesting that higher levels of independence may be related to lower adherence to prescribed medication. The facet component self-reliance is predictive of poor medication adherence. Discussion: The finding that higher self-reliance is associated with lower adherence in an older population deserves further investigation and clinical consideration.
Defining the Peer Advisor in the U.S. Study Abroad Context
Authors: Lo Stephanie
Published: April 2006

Peer advisor (PA) programs in study abroad offices have greatly increased in the past few years. Nevertheless, although many agree that PAs have many useful advantages, a clear definition of the PA within the study abroad context remains unavailable. Hence, the purpose of this pilot study is to find out how the PA is perceived by study abroad offices across the United States and what implications those perceptions hold. To address these two questions, this article specifically sought to find out PAs’ roles and responsibilities, what qualifications are required, and what type of training the PAs need to undergo as perceived and determined by study abroad office advisors. The article concludes with a preliminary definition of the study abroad PA and its implications.
Definitive-like erythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin
Authors: Chang Kai-Hsin , Nelson Angelique M. , Cao Hua , Wang Linlin , Nakamoto Betty , Ware Carol B. , Papayannopoulou Thalia
Published: April 2006

Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic marker emergence suggest that CD45+ hematopoiesis peaks at late D14EB differentiation stages, although low-level CD45- erythroid differentiation can be seen before that stage. By morphologic criteria, hES-derived erythroid cells were of definitive type, but these cells both at mRNA and protein levels coexpressed high levels of embryonic (ϵ) and fetal (γ) globins, with little or no adult globin (β). This globin expression pattern was not altered by the presence or absence of fetal bovine serum, vascular endothelial growth factor, Flt3-L, or coculture with OP-9 during erythroid differentiation and was not culture time dependent. The coexpression of both embryonic and fetal globins by definitive-type erythroid cells does not faithfully mimic either yolk sac embryonic or their fetal liver counterparts. Nevertheless, the high frequency of erythroid cells coexpressing embryonic and fetal globin generated from embryonic stem cells can serve as an invaluable tool to further explore molecular mechanisms.
Parameter estimation for stiff equations of biosystems using radial basis function networks
Authors: Matsubara Yoshiya , Kikuchi Shinichi , Sugimoto Masahiro , Tomita Masaru
Published: April 2006

Background

The modeling of dynamic systems requires estimating kinetic parameters from experimentally measured time-courses. Conventional global optimization methods used for parameter estimation, e.g. genetic algorithms (GA), consume enormous computational time because they require iterative numerical integrations for differential equations. When the target model is stiff, the computational time for reaching a solution increases further.

Results

In an attempt to solve this problem, we explored a learning technique that uses radial basis function networks (RBFN) to achieve a parameter estimation for biochemical models. RBFN reduce the number of numerical integrations by replacing derivatives with slopes derived from the distribution of searching points. To introduce a slight search bias, we implemented additional data selection using a GA that searches data-sparse areas at low computational cost. In addition, we adopted logarithmic transformation that smoothes the fitness surface to obtain a solution simply. We conducted numerical experiments to validate our methods and compared the results with those obtained by GA. We found that the calculation time decreased by more than 50% and the convergence rate increased from 60% to 90%.

Conclusion

In this work, our RBFN technique was effective for parameter optimization of stiff biochemical models.
Simplifying gene trees for easier comprehension
Authors: Lott Paul-Ludwig , Mundry Marvin , Sassenberg Christoph , Lorkowski Stefan , Fuellen Georg
Published: April 2006

Background

In the genomic age, gene trees may contain large amounts of data making them hard to read and understand. Therefore, an automated simplification is important.

Results

We present a simplification tool for gene trees called TreeSimplifier. Based on species tree information and HUGO gene names, it summarizes "monophyla". These monophyla correspond to subtrees of the gene tree where the evolution of a gene follows species phylogeny, and they are simplified to single leaves in the gene tree. Such a simplification may fail, for example, due to genes in the gene tree that are misplaced. In this way, misplaced genes can be identified. Optionally, our tool glosses over a limited degree of "paraphyly" in a further simplification step. In both simplification steps, species can be summarized into groups and treated as equivalent. In the present study we used our tool to derive a simplified tree of 397 leaves from a tree of 1138 leaves. Comparing the simplified tree to a "cartoon tree" created manually, we note that both agree to a high degree.

Conclusion

Our automatic simplification tool for gene trees is fast, accurate, and effective. It yields results of similar quality as manual simplification. It should be valuable in phylogenetic studies of large protein families. The software is available at http://www.uni-muenster.de/Bioinformatics/services/treesim/.
Design of microarray probes for virus identification and detection of emerging viruses at the genus level
Authors: Chou Cheng-Chung , Lee Te-Tsui , Chen Chun-Houh , Hsiao Hsiang-Yun , Lin Yi-Ling , Ho Mei-Shang , Yang Pan-Chyr , Peck Konan
Published: April 2006

Background

Most virus detection methods are geared towards the detection of specific single viruses or just a few known targets, and lack the capability to uncover the novel viruses that cause emerging viral infections. To address this issue, we developed a computational method that identifies the conserved viral sequences at the genus level for all viral genomes available in GenBank, and established a virus probe library. The virus probes are used not only to identify known viruses but also for discerning the genera of emerging or uncharacterized ones.

Results

Using the microarray approach, the identity of the virus in a test sample is determined by the signals of both genus and species-specific probes. The genera of emerging and uncharacterized viruses are determined based on hybridization of the viral sequences to the conserved probes for the existing viral genera. A detection and classification procedure to determine the identity of a virus directly from detection signals results in the rapid identification of the virus.

Conclusion

We have demonstrated the validity and feasibility of the above strategy with a small number of viral samples. The probe design algorithm can be applied to any publicly available viral sequence database. The strategy of using separate genus and species probe sets enables the use of a straightforward virus identity calculation directly based on the hybridization signals. Our virus identification strategy has great potential in the diagnosis of viral infections. The virus genus and specific probe database and the associated summary tables are available at http://genestamp.sinica.edu.tw/virus/index.htm
Flexible promoter architecture requirements for coactivator recruitment
Authors: Chiang Derek Y , Nix David A , Shultzaberger Ryan K , Gasch Audrey P , Eisen Michael B
Published: April 2006

Background

The spatial organization of transcription factor binding sites in regulatory DNA, and the composition of intersite sequences, influences the assembly of the multiprotein complexes that regulate RNA polymerase recruitment and thereby affects transcription. We have developed a genetic approach to investigate how reporter gene transcription is affected by varying the spacing between transcription factor binding sites. We characterized the components of promoter architecture that govern the yeast transcription factors Cbf1 and Met31/32, which bind independently, but collaboratively recruit the coactivator Met4.

Results

A Cbf1 binding site was required upstream of a Met31/32 binding site for full reporter gene expression. Distance constraints on coactivator recruitment were more flexible than those for cooperatively binding transcription factors. Distances from 18 to 50 bp between binding sites support efficient recruitment of Met4, with only slight modulation by helical phasing. Intriguingly, we found that certain sequences located between the binding sites abolished gene expression.

Conclusion

These results yield insight to the influence of both binding site architecture and local DNA flexibility on gene expression, and can be used to refine computational predictions of gene expression from promoter sequences. In addition, our approach can be applied to survey promoter architecture requirements for arbitrary combinations of transcription factor binding sites.
Bone erosions in rheumatoid arthritis can be repaired through reduction in disease activity with conventional disease-modifying antirheumatic drugs
Authors: Ideguchi Haruko , Ohno Shigeru , Hattori Hideaki , Senuma Akiko , Ishigatsubo Yoshiaki
Published: April 2006

We conducted the present study to determine whether repair of erosions occurs in patients with rheumatoid arthritis (RA) treated with conventional disease-modifying anti-rheumatic drugs (DMARDs) and to compare clinical characteristics between patients exhibiting and not exhibiting erosion repair. We included in the study a total of 122 RA patients who fulfilled the 1987 American College of Rheumatology criteria for RA; all patients had paired sequential radiographs of both hands and wrists showing erosive changes at baseline. Patients were classified into two groups according to the presence of repair of erosions at follow up, namely the 'repair observed' and 'repair not observed' groups. Clinical characteristics, disease activity, radiographic scores and treatment in the two groups were compared. Forty-four repairs were observed in 13 patients (10.7%). Compared with the repair not observed group, the functional class of the patients in the repair observed group was lower at baseline (P< 0.01) and the mean disease activity was lower at follow up (P< 0.005). The changes in radiographic scores per year (total radiographic score and erosion score) were lower (P< 0.05 andP< 0.01, respectively) in the repair observed group. No difference in treatment was observed. Repair of erosions was detected in 10.7% of RA patients treated with conventional DMARDs. Repairs were associated with low functional class at baseline and low disease activity at follow up. These observations support the importance of reduction in disease activity in RA patients. Because repair of erosions was detected in a substantial number of patients, assessment of erosion repair should be incorporated into the radiographic evaluation and scoring of RA.
The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes
Authors: Magne David , Palmer Gaby , Barton Jenny L , Mézin Francoise , Talabot-Ayer Dominique , Bas Sylvette , Duffy Trevor , Noger Marcus , Guerne Pierre-Andre , Nicklin Martin JH , Gabay Cem
Published: April 2006

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1β protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis.
Osteogenic protein 1 in synovial fluid from patients with rheumatoid arthritis or osteoarthritis: relationship with disease and levels of hyaluronan and antigenic keratan sulfate
Authors: Chubinskaya Susan , Frank Benjamin S , Michalska Margaret , Kumar Bhavna , Merrihew Charis A , Thonar Eugene J-MA , Lenz Mary Ellen , Otten Lori , Rueger David C , Block Joel A
Published: April 2006

The measurement of body fluid levels of biochemical markers in joint tissues has begun to provide clinically useful information. Synovial fluid (SF) plays an important role in articular joint lubrication, nutrition, and metabolism of cartilage and other connective tissues within the joint. The purpose of our study was to identify and characterize osteogenic protein 1 (OP-1) in SF from patients with rheumatoid arthritis (RA) or with osteoarthritis (OA) and to correlate levels of OP-1 with those of hyaluronan (HA) and antigenic keratan sulfate (AgKS). SF was aspirated from the knees of patients with either RA or OA and from the knees of asymptomatic organ donors with no documented history of joint disease. The presence of detectable OP-1 in SF was demonstrated by western blots with specific anti-pro-OP-1 and anti-mature OP-1 antibodies. Measurement of levels of OP-1, HA and AgKS was performed using ELISAs. OP-1 was identified in human SF in two forms, pro-OP-1 and active (mature) OP-1 – mature OP-1 being detected only in SF from OA patients and RA patients. Levels of OP-1 and HA were higher in RA patients than in OA patients and asymptomatic donors, while the level of AgKS was highest in SF from asymptomatic donors. Statistically significant differences were found between SF levels of OP-1 in RA and OA patients and between SF levels of AgKS among the three groups tested. The SF content of OP-1 tended to correlate positively with HA levels, but negatively with AgKS concentrations. In conclusion, the results of this study suggest that measurement of OP-1 in joint fluid may have value in the clinical evaluation of joint disease processes.
Euthanasia: the role of the psychiatrist
Authors: Naudts Kris , Ducatelle Caroline , Kovacs Jozsef , Laurens Kristin , Van Den Eynde Frederique , Van Heeringen Cornelis
Published: April 2006

Belgium has become one of the few countries in the world where euthanasia is legally allowed within a specific juridical framework. Even more unique is the inclusion of grounds for requesting euthanasia on the basis of mental suffering. Further refinement of the legal, medical and psychiatric approach to the issue is required in order to clear up essential practical and ethical matters. Psychiatrists and their professional organisations need to play a greater role in this ongoing debate and contribute from a clinical, scientific and ethical point of view.