bluuebunny/crossref_metadata_2025 huggingface dataset:
LA DYNAMIQUE DES RÉFORMES D'INDUSTRIES DE RÉSEAUX:LE CAS DE L'ÉLECTRICITÉ ET DES CHEMINS DE FER EN GRANDE‐BRETAGNE
Authors: Staropoli Carine , Yvrande‐Billon Anne
Published: January 2009

RÉSUMÉ**:  Cet article porte sur le design organisationnel des réformes d'industries de réseaux. Plus précisément, nous nous interrogeons sur la pertinence du modèle de déintégration verticale complète adopté par la Grande Bretagne dans les industries électrique et ferroviaire. Au regard de la rapiditéà laquelle les structures d'organisation initialement mises en place par les réformes ont été modifiées et compte tenu de la profondeur des transformations qu'elles ont subies, nous sommes en effet amenées à nous demander si le modèle de restructuration «radicale» des industries en réseaux est efficace et peut s'inscrire dans la durée ou bien s'il ne constitue qu'une étape transitoire vers un schéma d'organisation plus stable et peut‐être plus proche de la structure de gouvernance initiale.
THE KANTIAN ARGUMENT FOR CONSEQUENTIALISM
Authors: Otsuka Michael
Published: January 2009

A critical examination of Parfit's attempt to reconcile Kantian contractualism with consequentialism, which disputes his contention that the contracting parties would lack decisive reasons to choose principles that ground prohibitions against harming of the sort to which non‐consequentialists have been attracted.1
MIGHT KANTIAN CONTRACTUALISM BE THE SUPREME PRINCIPLE OF MORALITY?
Authors: Rosen Gideon
Published: January 2009

According to Parfit, the best version of Kantian ethics takes as its central principle Kantian Contractualism: the thesis that everyone ought to follow the principles whose universal acceptance everyone could rationally will. This paper examines that thesis, identifies a class of annoying counterexamples, and suggests that when Kantian Contractualism is modified in response to these examples, the resulting principle is too complex and ad hoc to serve as the ‘supreme principle of morality’.
AIDS stigma in health services in the Eastern Caribbean
Authors: Rutledge Scott Edward , Abell Neil , Padmore Jacqueline , McCann Theresa J.
Published: January 2009

Stigma obstructs HIV/AIDS prevention and care worldwide, including in the Caribbean, where the prevalence of AIDS is second only to sub‐Saharan Africa. To contextualise the experience of AIDS stigma in health services in Grenada and Trinidad and Tobago, we conducted eight focus groups with 51 people living with HIV/AIDS (PLHA), families, and service providers. Quasi‐deductive content analysis revealed consonance with Western and Northern conceptualisations of AIDS stigma wherein stigma is enacted upon marginalised populations and reinforced through psycho‐sociological processes comparing ‘in’ and ‘out’ groups. Socially constructed to be physically contagious and socially deviant, PLHA are scorned by some service providers, especially when they are perceived to be gay or bisexual. PLHA and providers identified passive neglect and active refusal by hospital and clinic staff to provide care to PLHA. Institutional practices for safeguarding patient confidentiality are perceived as marginally enforced. Interventions are needed to reduce provider stigma so the public will access HIV testing and PLHA will seek treatment.
A Functional Approach to Diversity Profiles
Authors: Gattone Stefano A. , Battista Tonio Di
Published: January 2009

Diversity plays a central role in ecological theory and its conservation and management are important issues for the wellbeing and stability of ecosystems. The aim of this work is to provide a reliable theoretical framework for performing statistical analysis on ecological diversity by means of the joint use of diversity profiles and functional data analysis. We point out that ecological diversity is a multivariate concept as it is a function of the relative abundances of species in a biological community. For this, several researchers have suggested using parametric families of indices of diversity for obtaining more information from the data. Patil and Taillie introduced the concept of intrinsic diversity ordering which can be determined by using the diversity profile. It may be noted that the diversity profile is a non-negative and convex curve which consists of a sequence of measurements as a function of a given parameter. Thus, diversity profiles can be explained through a process that is described in a functional setting. Recent developments in environmental studies have focused on the opportunity to evaluate community diversity changes over space and/or correlation of diversity with environmental characteristics. For this, we develop an innovative analysis of diversity based on a functional data approach. Whereas conventional statistical methods process data as a sequence of individual observations, functional data analysis is designed to process a collection of functions or curves. Moreover, unconstrained models may lead to negative and/or non-convex estimates for the diversity profiles. To overcome this problem, a transformation is proposed which can be constrained to be non-negative and convex. We focus on some applications showing how functional data analysis provides an alternative way of understanding biological diversity and its interaction with natural and/or human factors.
A Multifaceted Sensitivity Analysis of the Slovenian Public Opinion Survey Data
Authors: Beunckens Caroline , Sotto Cristina , Molenberghs Geert , Verbeke Geert
Published: January 2009

Many models to analyse incomplete data have been developed that allow the missing data to be missing not at random. Awareness has grown that such models are based on unverifiable assumptions, in the sense that they rest on the (incomplete) data only in part, but that inferences nevertheless depend on what the model predicts about the unobserved data, given the observed data. This explains why, nowadays, considerable work is being devoted to assess how sensitive models for incomplete data are to the particular model chosen, a family of models chosen and the effect of (a group of) influential subjects. For each of these categories, several proposals have been formulated, studied theoretically and/or by simulations, and applied to sets of data. It is, however, uncommon to explore various sensitivity analysis avenues simultaneously. We apply a collection of such tools, some after extension, to incomplete counts arising from cross-classified binary data from the so-called Slovenian public opinion survey. Thus for the first time bringing together a variety of sensitivity analysis tools on the same set of data, we can sketch a comprehensive sensitivity analysis picture. We show that missingness at random estimates of the proportion voting in favour of independence are insensitive to the precise choice of missingness at random model and close to the actual plebiscite results, whereas the missingness not at random models that are furthest from the plebiscite results are vulnerable to the influence of outlying cases. Our approach helps to illustrate the value of comprehensive sensitivity analysis. Ideas are formulated on the methodology’s use beyond the data analysis that we consider.
A Required Yield Theory of Stock Market Valuation and Treasury Yield Determination
Authors: Faugère Christophe , Van Erlach Julian
Published: January 2009

Stock market valuation and Treasury yield determination are consistent with the Fisher effect (1896) as generalized byDarby (1975)andFeldstein (1976). The U.S. stock market (S&P 500) is priced to yield ex‐ante areal after‐taxreturn directly related to real long‐term GDP/capita growth (therequired yield). Elements of our theory show that: (1) real after‐tax Treasury and S&P 500 forward earnings yields are stationary processes around positive means; (2) the stock market is indeed priced as the present value of expected dividends with the proviso that investors are expecting fast mean reversion of the S&P 500nominalgrowth opportunities to zero. Moreover, (3) the equity premium is mostly due to business cycle risk and is a direct function of below trend expected productivity, where productivity is measured by the growth in book value of S&P 500 equity per‐share. Inflation and fear‐based risk premia only have a secondary impact on the premium. The premium is always positive or zero with respect to long‐term Treasuries. It may be negative for short‐term Treasuries when short‐term productivity outpaces medium and long run trends. Consequently: (4) Treasury yields are mostly determined in reference to the required yield and the business cycle risk premium; (5) the yield spread is largely explained by the differential of long‐term book value per share growth vs. near term growth, with possible yield curve inversions. Finally, (6) the Fed model is partially validated since both the S&P 500 forward earnings yield and the ten‐year Treasury yield are determined by a common factor: the required yield.
Transparency of Central Bank Preferences
Authors: Hahn Volker
Published: January 2009

In this paper, we examine whether the transparency of the central bank’s preferences is desirable. We make two major points. First, in the literature on preference transparency variance-reduction frameworks are often adopted. As a consequence a change in the degree of transparency affects the magnitude of information asymmetries, but at the same time it implies a rather arbitrary effect on the distribution of preferences. We present a clean framework without this problem. Second, using a very general specification of shocks to the central bank’s preferences, we show that society prefers transparency if it sufficiently values the employment target, whereas it prefers opacity if it estimates inflation as sufficiently important.
A Soft Budget Constraint Explanation for the Venture Capital Cycle
Authors: Gebhardt Georg
Published: January 2009

We explore why venture capital funds limit the amount of capital they raise and do not reinvest the proceeds. This structure is puzzling because it leads to a succession of several funds financing each new venture, which multiplies the well-known agency problems. We argue that an inside investor cannot provide a hard budget constraint while a less informed outsider can. Therefore, the venture capitalist delegates the continuation decision to the outsider by ex ante restricting the amount of capital he has under management. The soft budget constraint problem becomes the more important the higher the entrepreneur’s private benefits are and the higher the probability of failure of a project is.
Evaluation of the clinical and immunohistological efficacy of the 585‐nm pulsed dye laser in the treatment of psoriasis
Authors: Noborio R , Kurokawa M , Kobayashi K , Morita A
Published: January 2009

Background  The 585‐nm pulsed dye laser (PDL) therapy is useful for the patients with psoriasis. PDL treatment is based on selective photothermolysis of the dermal vasculature.

Objective  The objectives of this study were to evaluate the clinical and immunohistological effects of PDL on psoriasis and to examine the association between psoriatic dermal vasculature and the clinical effects.

Methods  Eleven patients with recalcitrant psoriasis were treated with 585‐nm PDL. Biopsy specimens obtained before and after treatment were stained with CD31. All microvessels to the depth of 400 µm from the rete ridge were counted and the internal diameters were measured.

Results  The mean percent reduction of plaque severity score was 42. The mean microvessel count decreased significantly from 63 to 35.6 (P < 0.001). There was a strong positive correlation between the plaque severity score and microvessel number (P < 0.001) and a strong negative correlation between the microvessel count of an untreated area and degree of the change in the microvessel count after treatment (P = 0.005).

Conclusions  The findings of this study suggest that PDL treatment improves psoriasis. Moreover, PDL treatment decreased the number of dermal papillary microvessels. Dermal papillary microvessels are important pathogenetic targets of psoriasis, and PDL therapy, which selectively targets superficial vessels, is therefore a valid therapeutic approach.

Conflicts of interest

None declared
Disentangling effects of auditory distraction and of stimulus‐response sequence
Authors: Roeber Urte , Berti Stefan , Müller Dagmar , Widmann Andreas , Schröger Erich
Published: January 2009

When we pay attention to one task, irrelevant changes may interfere. The effect of changes on behavioral and electrophysiological responses has been studied in two separate research fields: Research on Distraction states that a rare irrelevant change takes attention away from the primary task. Research on Sequences states that any change in stimulus or response incurs a cost or benefit depending on the kind of change. To disentangle distraction from sequence effects, we made task‐irrelevant changes rare in one condition and frequent in another while also assessing stimulus and response changes from trial to trial. Participants used key presses to classify syllables presented in two different, irrelevant voice pitches. We found that distraction and sequence interacted to alter reaction times and errors on the primary task and also to alter ERP markers of distraction (P3a). The sequential effects cannot, however, fully account for distraction.
Interaction, inclusion and students with profound and multiple disabilities: towards an agenda for research and practice
Authors: Arthur‐Kelly Michael , Foreman Phil , Bennett Deone , Pascoe Sue
Published: January 2009

The needs of students with profound and multiple disabilities (PMD) have received more attention in the educational research and best practice literature over the past decade, especially in relation to the importance of maximising their social and communicative engagement. However, perhaps as a function of their low incidence rate and resultant difficulties in obtaining research funding, there appears to be little in the way of a coherent vision for research in the international literature. In this paper we argue the need for a systematic programme of research into the nature of learning processes and outcomes for members of this group. Several issues emerge from a review of selected literature and from some recent observational data and descriptive case studies collected in special and inclusive classrooms. First, there is the importance of identifying ways of better understanding the complex experiences of members of this population, with particular attention to the ongoing contribution of behaviour state assessment as a means of measuring individual alertness and responsiveness. We argue that improved uptake of this approach will do much to advance our knowledge of life quality for this population and assist in more fully evaluating the effectiveness of educational interventions. Second, we explore the potential of social and communicative engagement in a variety of settings as a means of enhancing learning and participation in this group. We suggest that interpersonal variables are the key to improvements in educational support for this vulnerable group. Potential directions in research and practice are explored.
Roles of protein kinase Cα isozyme in the regulation of oxidative stress and neuropeptide Y gene expression in phenylpropanolamine‐mediated appetite suppression
Authors: Kuo Dong‐Yih , Yang Shun‐Fa , Chu Shu‐Chen , Chen Chin‐Hsiu , Hsieh Yih‐Shou
Published: January 2009

Hypothalamic neuropeptide Y (NPY) is an appetite stimulant in the brain. Although regulation of NPY expression has been reported to contribute to the appetite‐suppressing effect of phenylpropanolamine (PPA), it is still unknown if protein kinase C (PKC) is involved in this effect. Rats were daily treated with PPA for 4 days. Changes in food intake, hypothalamic NPY, PKC, and proopiomelanocortin (POMC) mRNA levels were assessed and compared. Results showed that the NPY gene was down‐regulated following PPA treatment, which was parallel with the decrease of feeding. Moreover, several isotypes of PKC mRNA level (α, βI, βII, γ, δ, η, λ, ε, and ζ) were changed. Among these, α, δ, and λ PKC were up‐regulated along with POMC gene expression which coincided with down‐regulation of the NPY gene. To further determine if PKCα was involved, infusions of antisense oligonucleotide into the cerebroventricle were performed at 1 h before daily PPA treatment in free‐moving rats. Results showed that PKCα knock‐down could modify both anorexia induced by PPA and the NPY mRNA levels. Moreover, PKCα knock‐down could also modify superoxide dismutase (SOD) gene expression. It is suggested that PKCα participates in the regulation of PPA‐mediated appetite suppression via the modulation of NPY and SOD gene expression.
Evaluation of Local Ecological Knowledge as a Method for Collecting Extensive Data on Animal Abundance
Authors: ANADÓN JOSÉ DANIEL , GIMÉNEZ ANDRÉS , BALLESTAR RUBÉN , PÉREZ IRENE
Published: January 2009

Abstract: The use of local ecological knowledge (LEK) has been advocated for biodiversity monitoring and management. To date, however, it has been underused in studying wild populations of animals and, particularly, in obtaining quantitative abundance estimates. We evaluated LEK as a tool for collecting extensive data on local animal abundance and population trends. We interviewed shepherds in southeastern Spain, asking them to estimate the local abundance of the terrestrial tortoiseTestudo graeca. We quantified reliability of abundance estimates derived from interviews by comparing them with those obtained from standard field‐sampling protocols (distance sampling). We also explored the complementarity of these 2 approaches. LEK provided high‐quality and low‐cost information about both distribution and abundance ofT. graeca. Interviews with shepherds yielded abundance estimates in a much wider range than linear transects, which only detected the species in the upper two‐thirds of its abundance range. Abundance estimates from both methodologies showed a close relationship. Analysis of confidence intervals indicated local knowledge could be used to estimate mean local abundances and to detect mean population trends. A cost analysis determined that the information derived from LEK was 100 times cheaper than that obtained through linear‐transect surveys. Our results should further the use of LEK as a standard tool for sampling the quantitative abundance of a great variety of taxa, particularly when population densities are low and traditional sampling methods are expensive or difficult to implement.
Thalamofrontal circuitry and executive dysfunction in recent‐onset juvenile myoclonic epilepsy
Authors: Pulsipher Dalin T. , Seidenberg Michael , Guidotti Leslie , Tuchscherer Victoria N. , Morton Jared , Sheth Raj D. , Hermann Bruce
Published: January 2009

Purpose:  Thalamofrontal abnormalities have been identified in chronic primary generalized epilepsy, specifically in juvenile myoclonic epilepsy (JME). These regions also underlie executive functioning, although their relationship has yet to be examined in JME. This study examined the relationship between thalamic and frontal volumes and executive function in recent‐onset JME compared to healthy control subjects and recent‐onset benign childhood epilepsy with centrotemporal spikes (BCECTS), a syndrome not typically associated with thalamocortical or executive dysfunction.

Methods:  Twenty children with recent‐onset JME were compared to 51 healthy controls and 12 children with BCECTS using quantitative magnetic resonance imaging (MRI) and measures of executive abilities. Quantitative thalamic and frontal volumes were obtained through semi‐automated software. Subtests from the Delis–Kaplan Executive Function System (D‐KEFS) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to measure executive function.

Results:  Executive functions were impaired in JME subjects compared to control and BCECTS subjects. Subjects with JME had significantly smaller thalamic volumes and more frontal cerebrospinal fluid (CSF) than control and BCECTS subjects. Thalamic and frontal volumes were significantly related to executive functioning in the JME group, but not in the other two groups.

Discussion:  Children with JME have significant executive dysfunction associated with significantly smaller thalami and more frontal CSF. Children with recent‐onset BCECTS do not display the same pattern. Frontal and thalamic volumes appear to mediate the relationship between executive functioning and brain structure in JME.
Measuring the Information Content of the Beige Book: A Mixed Data Sampling Approach
Authors: ARMESTO MICHELLE T. , HERNÁNDEZ‐MURILLO RUBÉN , OWYANG MICHAEL T. , PIGER JEREMY
Published: January 2009

Studies of the predictive ability of the Federal Reserve's Beige Book for aggregate output and employment have proven inconclusive. This might be attributed, in part, to its irregular release schedule. We use a model that allows for data sampling at mixed frequencies to analyze the predictive power of the Beige Book. We find that the Beige Book's national summary and District reports predict GDP and aggregate employment and that most District reports provide information content for regional employment. In addition, there appears to be an asymmetry in the predictive content of the Beige Book language.
Monetary Policy with Heterogeneous and Misspecified Expectations
Authors: BERARDI MICHELE
Published: January 2009

In the recent literature on monetary policy and learning, it has been suggested that private sector's expectations should play a role in the policy rule implemented by the central bank, as they could improve the ability of the policymaker to stabilize the economy. Private sector's expectations, in these studies, are often taken to be homogeneous and rational, at least in the limit of a learning process. In this paper, instead, we consider the case in which private agents are heterogeneous in their expectations formation mechanisms and hold heterogeneous expectations in equilibrium. We investigate the impact of this heterogeneity in expectations on central bank's policy implementation and on the ensuing economic outcomes, and the general result that emerges is that the central bank should disregard inaccurate private sector expectations and solely base its policy on the accurate ones.
The Euro Changeover and Its Effects on Price Transparency and Inflation
Authors: DZIUDA WIOLETTA , MASTROBUONI GIOVANNI
Published: January 2009

Despite the expectations of economists that the euro changeover would have no effect on prices, European consumers perceived the opposite. To shed some light on this puzzle, we develop a model of imperfect information in which cheaper goods experience higher price growth after the changeover. Retailers, aware of consumers' difficulties in adopting the new currency, use currency changeovers to increase profits by increasing prices. The lower the price transparency after the changeover, the higher the euro‐related inflation. Using data on inflation (Eurostat) and price levels (Economist Intelligence Unit), we show that although the euro changeover did not significantly increase inflation, it nevertheless had a distortionary effect on prices. After the changeover, cheaper goods had higher inflation, and this effect was stronger in countries in which people found dealing with the new currency problematic.
Political Influence and Declarations of Bank Insolvency in Japan
Authors: IMAI MASAMI
Published: January 2009

This paper investigates how politics affects bank supervision by examining determinants of bank failures in Japan during 1999–2002, a period during which bank regulators were called upon to resolve insolvent banks in preparation for the lifting of a blanket deposit guarantee. The empirical results suggest that Japan's bank regulators had tendency to delay declarations of insolvency in prefectures that supported senior politicians of the ruling Liberal Democratic Party (LDP). This result, which is robust to a host of bank‐level and prefecture‐level controls, suggests that bank supervision is prone to political influence that delays efficient resolution of insolvency.
Inflation Targeting Matters: Evidence from OECD Economies' Sacrifice Ratios
Authors: GONÇALVES CARLOS EDUARDO S. , CARVALHO ALEXANDRE
Published: January 2009

Using data from OECD economies, we show that inflation targeters suffered smaller output losses during disinflations when compared to nontargeters. We also study why some countries choose to inflation target while others do not and find that higher average inflation and smaller debt levels render the adoption of the regime more likely. Applying Heckman's procedure to control for selection bias does not alter the link between inflation targeting and less costly disinflations.
International Pricing in a Generalized Model of Ideal Variety
Authors: HUMMELS DAVID , LUGOVSKYY VOLODYMYR
Published: January 2009

We examine international markups and pricing in a generalized version of an “ideal variety” model. In this model, entry causes crowding in variety space, so that the marginal utility of new varieties falls as market size grows. Crowding is partially offset by income effects, as richer consumers will pay more for varieties closer matched to their ideal types. We show theoretically and confirm empirically that declining marginal utility of new varieties results in: a higher own‐price elasticity of demand (and lower prices) in large countries and a lower own‐price elasticity of demand (and higher prices) in rich countries. The model is also useful for generating facts from the literature regarding cross‐country differences in the rate of variety expansion.
New directions in host modulation for the management of periodontal disease
Authors: Bhatavadekar Neel B. , Williams Ray C.
Published: January 2009

Background: New strategies for periodontal disease management have been emerging as more is learned about the role of the host response. Our increasing understanding of inflammation and its resolution has opened the door to the study of new periodontal treatment strategies. This commentary examines periodontal disease in light of a new understanding of the role of inflammation in disease expression, thus setting the stage for the development of new prevention and treatment strategies of a widespread disease.

Methods: We examined current publications and focused on articles relating to anti‐inflammatory and pro‐resolution mechanisms in periodontal disease.

Results: Recent research has examined the inflammatory and resolution cascade in greater detail while looking at endogenous and exogenous mediators that can be utilized to achieve therapeutic end‐points. The possible introduction of “resolution indices” for drug testing warrants a new look at pharmacologic agents that might have been overlooked for their beneficial effects in periodontal disease treatment.

Conclusion: The emerging awareness of inflammation and its control in periodontal disease management underscores the importance of exploring inflammatory pathways and mediators, thus exploring new ways to control inflammation. This direction of research promises a new era in drug discovery and therapeutics for periodontal disease treatment.
Relation of body mass index, periodontitis and Tannerella forsythia
Authors: Haffajee Anne D. , Socransky Sigmund Sidney
Published: January 2009

Objective: To determine if there were differences in periodontal status and the composition of the subgingival microbiota in individuals who exhibited different body mass indices (BMI).

Material and Methods: One hundred and twenty‐one periodontally healthy/gingivitis and 574 chronic periodontitis subjects had height and weight determined and were measured for probing pocket depth, clinical attachment level, bleeding on probing, gingival redness and presence of visible plaque. Subgingival plaque samples taken from each tooth were individually analysed for their content of 40 bacterial species using checkerboard DNA–DNA hybridization.

Results: Crude odds ratios (ORs) [95% confidence interval (CI)] of overweight and obese individuals exhibiting periodontitis were 3.1 (1.9–4.8) and 5.3 (2.8–9.5), respectively, when compared with subjects with normal BMI. Logistic regression analysis indicated an OR (95% CI) of 2.3 (1.2–4.5) for an obese subject to exhibit periodontitis after adjusting for age, gender and smoking status. Individuals <46.8 years (median age) were responsible for this association. Only Tannerella forsythia differed significantly in proportions among BMI groups and was significantly higher in obese periodontally healthy/gingivitis individuals.

Conclusion: The data suggest that an overgrowth of T. forsythia occurs in the subgingival biofilms of periodontally healthy, overweight and obese individuals that might put them at risk for initiation and progression of periodontitis.
Mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome
Authors: KURODA NAOTO , AMANO SHINJI , SHIOTSU TOMOYUKI , TAMURA MASATO , HES ONDREJ , MICHAL MICHAL , LEE GANG‐HONG
Published: January 2009

We here present a case of mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome. A 20‐year‐old Japanese man with a mass in the left inguinal region underwent orchidectomy as a left testicular tumor was suspected. Histology showed a mixed germ‐cell tumor with embryonal carcinoma and yolk sac tumor with syncytiotrophoblastic giant cells occurring in a cryptorchid testis. Chromosomal analysis of peripheral lymphocytes disclosed a karyotype of 47,XY,+21[20]. Our case provides further evidence that these three conditions—Down's syndrome, cryptorchidism and testicular germ cell tumor—may be closely associated. To our knowledge this is the first case of mixed germ cell tumor arising in a patient with Down's syndrome and cryptorchidism.
Atrial natriuretic peptide and CD34 overexpression in human idiopathic dilated cardiomyopathies
Authors: ARDIZZONE N. , CAPPELLO F. , DI FELICE V. , RAPPA F. , MINERVINI F. , MARASÀ S. , MARASÀ L. , RABL W. , ZUMMO G. , SERGI C.
Published: January 2009

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause characterized by ventricular chamber enlargement with impaired contractile function. In familial forms of IDCM, mutations of genes coding for cytoskeletal proteins related to force transmission, such as dystrophin, cardiac actin, desmin, and δ‐sarcoglycan, have been identified. Here, we report the data of a retrospective investigation carried out to evaluate the expression of atrial natriuretic peptide (ANP), CD34, troponin T and nestin in the myocardium of patients affected with IDCM. Formalin‐fixed and paraffin‐embedded consecutive tissue sections from the ventricular wall of 10 human normal hearts (NH) following forensic autopsy and 22 IDCM (living explanted hearts) were studied using primary monoclonal antibodies against ANP, CD34, troponin T and nestin by immunohistochemistry. Myocardial fibers were counted independently by three pathologists. Statistics included analysis of variance, log‐rank test for Kaplan‐Meier analysis, and kappa assessment for intra‐ and inter‐observer variability. ANP and CD34 were significantly overexpressed in IDCM compared to NH (p<0.05). Conversely, troponin T and nestin expression levels did not show significant variation. Inter‐observer kappa statistics showed a value of 0.87 and intra‐observer kappa statistics a value of 0.98. Evaluation of the marker distribution in the myocardium of patients with IDCM CD34 expression curve was similar to that of troponin T (p<0.0001), although two groups could be identified. Patients with a difference of more than 20 myocardial fibers in expression of CD34 and troponin T had a somewhat less favorable survival although the difference was not significant. The analysis of cells positive for troponin T resulted in a similar number of cardiac fibers between NH and IDCM. This is in agreement with cardiac enlargement present in IDCM, which is due to ventricular dilatation rather than increased number of myocytes. Moreover, the expression of nestin, a marker of activation of myocardial precursors, did not change either, and this may confirm that there are no hyperplastic phenomena in the IDCM pathogenesis. The increase in ANP‐positive cells in IDCM could be a consequence of neurohormonal activation due to a decline in the impaired myocyte contractility. Furthermore, since it was already shown that ANP could be important in the control of vascular remodeling, we postulated that the increase in CD34‐positive cells might be functionally correlated with the increase in ANP production. Differential expression of CD34 and troponin T might be used in future studies to evaluate their prognostic value.
Altered expression of CK7 and CK20 in preneoplastic and neoplastic lesions in ulcerative colitis
Authors: STENLING ROGER , LINDBERG JAN , RUTEGÅRD JÖRGEN , PALMQVIST RICHARD
Published: January 2009

This study is based on all patients with ulcerative colitis from a defined catchment area in Northern Sweden in a still ongoing colonoscopy surveillance programme, which started in 1977. From this material we selected tissue from eight groups of patients consisting of normal control biopsies (5), inactive colitis (10), active colitis (10), findings of low‐grade dysplasia (10), high‐grade dysplasia (6), aneuploidy (without dysplasia and with subsequent dysplasia) (10), and ulcerative colitis‐associated cancers (5). The samples were evaluated according to immunohistochemical expression of CK7 and CK20. Colonic mucosa from normal controls and inactive colitis was found to be completely negative for CK7. In 9 out of 10 patients with active colitis, CK7 was sparsely expressed in a patchy manner and connected with active epithelial inflammatory areas. 7 out of 10 patients with low‐grade dysplasia and 3 out of 6 with high‐grade dysplasia were positive for CK7. Samples with aneuploidy without dysplasia were completely negative, while 2 out of 6 showing subsequent dysplasia were positive. Of the five cancers, two were positive for CK7. CK20 was expressed in nearly all samples but relatively more in the lower part of the crypts in neoplasia‐associated lesions. Our results indicate a possible relationship between expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. Further studies are needed to elucidate whether these findings have clinical significance.
Pyrosequencing of a short hypervariable 16S rDNA fragment for the identification of nontuberculous mycobacteria—a comparison with conventional 16S rDNA sequencing and phenotyping
Authors: CRISTEA‐FERNSTRÖM MARIANA , OLOFSSON MARGARETHA , CHRYSSANTHOU ERJA , JONASSON JON , PETRINI BJÖRN
Published: January 2009

Conventional methods for identification of nontuberculous mycobacteria (NTM) are often inexact and time consuming. Sequencing of bacterial 16S rDNA is accurate, rapid and effective. We have retrospectively evaluated the discriminative power of pyrosequencing of a short hypervariable 16S rDNA fragment as a simple and rapid tool for NTM characterization. A series of 312 clinical NTM isolates, excluding the M. avium/intracellulare complex, was investigated. When species could not be resolved by sequencing alone, growth rate and pigment production were also examined. 54% (170/312) of the isolates were unambiguously identified by both methods. An additional 14% (45/312) were directly identified to species by conventional 16S rDNA sequencing but needed complementary phenotypic analysis when examined by pyrosequencing. The remaining 31% (97/312) needed additional phenotypic analysis for both sequencing methods. We consider the pyrosequencing procedure to be a useful alternative for the identification of several NTM species, and a versatile tool for the characterization of clinical NTM isolates. At times it requires additional tests for definite species diagnosis and correct identification.
Dietary sugars, serum and the biocide chlorhexidine digluconate modify the population and structural dynamics of mixed Candida albicans and Escherichia coli biofilms
Authors: THEIN Z. M. , SAMARANAYAKE Y. H. , SAMARANAYAKE L. P.
Published: January 2009

Despite the increasing recognition of the role played by mixed species biofilms in health and disease, the behavior and factors modulating these biofilms remain elusive. We therefore compared the effect of serum, two dietary sugars (sucrose and galactose) and a biocide, chlorhexidine digluconate, on a dual species biofilm (DSB) of Candida albicans and Escherichia coli and, their single species biofilm (SSB) counterparts. Both modes of biofilm growth on polystyrene plastic surfaces were quantified using a viable cell count method and visualized using confocal scanning laser microscopy (CSLM). Present data indicate that co‐culture of C. albicans with varying initial concentrations of E. coli leads to a significant inhibition of yeast growth (r=−0.964; p<0.001). Parallel ultrastructural studies using CSLM and a Live/Dead stain confirmed that E. coli growth rendered blastospores and hyphal yeasts non‐viable in DSB. SSB of C. albicans showed pronounced growth when its growth surface was pretreated with serum and by sugar supplements in the incubating medium (p<0.05). Intriguingly, C. albicans in DSB was more resistant to the antiseptic effect of chlorhexidine digluconate. Taken together, the current data elucidate some features of the colonization resistance offered by bacteria in mixed bacterial/fungal habitats and how such phenomena may contribute to the development of fungal superinfection during antimicrobial therapy.
Performance of commercial latex agglutination tests for the differentiation of Candida dubliniensis and Candida albicans in routine diagnostics
Authors: CHRYSSANTHOU E. , FERNANDEZ V. , PETRINI B.
Published: January 2009

Candida dubliniensis is phenotypically similar to Candida albicans and may therefore be underdiagnosed in the clinical microbiology laboratory. The performance of Bichro‐Dubli latex agglutination test for rapid species identification of C. dubliniensis was prospectively evaluated on 111 vaginal and 118 respiratory isolates. These had presumptively been identified as C. albicans/C. dubliniensis by their green colonies on CHROMagar Candida plates. Bichro‐Dubli test identifed 2 (1.8%) vaginal and 6 (5.1%) respiratory isolates as C. dubliniensis. The test was also positive for 37 C. dubliniensis control strains characterised by 18S‐28S DNA‐sequencing. Bichro‐Dubli test is thus a sensitive and accurate tool for rapid diagnostics in routine laboratories.
Research in practice: diagnosis of subepidermal autoimmune bullous disorders
Authors: Schmidt Enno , Zillikens Detlef
Published: January 2009

Subepidermal autoimmune bullous disorders are a heterogeneous group of diseases that are associated with autoantibodies to hemidesmosomal proteins (pemphigoid group, epidermolysis bullosa acquisita) or epidermal/tissue transglutaminase (dermatitis herpetiformis). Characterization of the target antigens has led to the description of novel entities such as anti‐p200 pemphigoid and has greatly facilitated the diagnosis of these diseases. Precise identification of target antigens is of therapeutic relevance since treatment options may greatly differ between these disorders. By the use of various in vitro and in vivo systems, the pathogenic relevance of autoantibodies to different hemidesmosomal constituents, including BP180 (type XVII collagen), laminin 332 (laminin 5), α6β4 integrin, and type VII collagen has been demonstrated. The translation of this basic scientific work has subsequently led to the development of specific autoantibody detection systems that are not only of diagnostic use but also allow the monitoring of circulating autoantibody levels during the course of the disease and thus are helpful in guiding treatment decisions in these patients.
CREDO: A Protein–Ligand Interaction Database for Drug Discovery
Authors: Schreyer Adrian , Blundell Tom
Published: January 2009

Harnessing data from the growing number of protein–ligand complexes in the Protein Data Bank is an important task in drug discovery. In order to benefit from the abundance of three‐dimensional structures, structural data must be integrated with sequence as well as chemical data and the protein–small molecule interactions characterized structurally at the inter‐atomic level. In this study, we present CREDO, a new publicly available database of protein–ligand interactions, which represents contacts as structural interaction fingerprints, implements novel features and is completely scriptable through its application programming interface. Features of CREDO include implementation of molecular shape descriptors with ultrafast shape recognition, fragmentation of ligands in the Protein Data Bank, sequence‐to‐structure mapping and the identification of approved drugs. Selected analyses of these key features are presented to highlight a range of potential applications of CREDO. The CREDO dataset has been released into the public domain together with the application programming interface under a Creative Commons license at http://www‐cryst.bioc.cam.ac.uk/credo. We believe that the free availability and numerous features of CREDO database will be useful not only for commercial but also for academia‐driven drug discovery programmes.
Novel Reticular Cyclen‐Based Polymer as Gene Vector in DNA Transfection
Authors: Zhou Li‐Hong , Yang Mu , Zhou Hong , Zhang Ji , Li Kun , Xiang Yong‐Zhe , Wang Na , Tian Yun‐Fei , Yu Xiao‐Qi
Published: January 2009

This study provided an experimental evidence for the use of cyclen (1, 4, 7, 10‐tetraazacyclododecane)‐based polymer for gene delivery. The interesting interaction of the polymer with plasmid DNA was studied by using fluorescence titration, circular dichroism spectra, agarose gel electrophoresis and atomic force microscopy. It was found that polyplex was formed between the polycation and plasmid DNA. The results demonstrated that the cyclen‐based polymer could act as non‐viral gene vector with relatively low cytotoxicity.
Antimicrobial and Cytolytic Activities and Plausible Mode of Bactericidal Action of the Cell Penetrating Peptide Penetratin and Its Lys‐linked Two‐Stranded Peptide
Authors: Zhu Wan Long , Shin Song Yub
Published: January 2009

The cell penetrating peptide, penetratin (RQIKIWFQNRRMKWKK‐NH2) showed potent antimicrobial activity (MIC: 0.5–4 μm) without any cytotoxicity against mammalian cells. This study investigated the effect of linking together two peptide chains of penetratin on antimicrobial and cytolytic activities and plausible mode of bactericidal action. Two‐stranded penetratin was prepared by a simultaneous solid‐phase synthesis of the two strands of a single lysine residue attached to the solid support. Two‐stranded penetratin markedly increased cytolytic activity against human erythrocytes and NIH‐3T3 mouse fibroblast cells without a significant effect on antimicrobial activity. This finding suggested that penetratin is active as a monomer to bacterial cells but as an oligomer to mammalian cells. Circular dichroism analysis revealed that the α‐helical content of the membrane‐bound penetratin was unaffected by two‐stranded Lys‐linkage. Penetratin had very weak ability in the depolarization of membrane potential of intact Staphylococcus aureus cells and the fluorescent dye leakage of calcein‐entrapped negatively charged bacterial membrane‐mimicking vesicles. In contrast, two‐stranded penetratin significantly caused membrane depolarization and dye leakage. These results suggest that the two‐stranded penetratin induces a significant change in its mode of bactericidal action from the intracellular‐target mechanism to the membrane‐targeting mechanism.
Thyroid hormone β receptor activation has additive cholesterol lowering activity in combination with atorvastatin in rabbits, dogs and monkeys
Authors: Ito BR , Zhang B‐H , Cable EE , Song X , Fujitaki JM , MacKenna DA , Wilker CE , Chi B , Van Poelje PD , Linemeyer DL , Erion MD
Published: January 2009

Mandarin translation of abstract

Background and purpose: Thyroid hormone receptor (TR) agonists are in clinical trials for the treatment of hypercholesterolaemia. As statins are the standard of clinical care, any new therapies must have adjunctive activity, when given in combination with statins. As already known for the statins, the cholesterol lowering effect of TR activation involves increased expression of the low‐density lipoprotein receptor. Using animal models, we tested whether TR activation would have additive cholesterol lowering activity in the presence of effective doses of a statin.

Experimental approach: We evaluated the activity of a liver‐targeted prodrug, MB07811, of a novel TH receptor β agonist, MB07344, as monotherapy and in combination with atorvastatin in rabbits, dogs and monkeys.

Key results: In rabbits, MB07344 (i.v.) decreased total plasma cholesterol (TPC) comparable to that achieved with a maximally effective dose of atorvastatin (p.o.). The addition of MB07344 to atorvastatin resulted in a further decrease in TPC. Similarly, the addition of MB07811 (p.o.) to atorvastatin treatment decreased TPC beyond the level achieved with either agent as monotherapy. In dogs and monkeys, atorvastatin and MB07811 were administered as monotherapy or in combination. Consistent with the rabbit studies, the combination treatment caused a greater decrease in TPC than either MB07811 or atorvastatin administered as monotherapy.

Conclusions and implications: We conclude that the effects of MB07811 and atorvastatin in lowering cholesterol are additive in animals. These results would encourage and support the demonstration of similarly improved efficacy of combination versus monotherapy with such agents in the clinic.

Mandarin translation of abstract
Erythrocytic pyruvate kinase deficiency and AB blood types in Australian Abyssinian and Somali cats
Authors: Barrs VR , Giger U , Wilson B , Chan CTT , Lingard AE , Tran L , Seng A , Canfield PJ , Beatty JA
Published: January 2009

Objective  To determine the frequency of the mutant pyruvate kinase (PK) allele, haematological parameters and AB blood types of Abyssinian and Somali cats in Australia.

Design  Complete blood cell and reticulocyte counts, DNA PK mutation testing and blood typing were performed in all cats.

Results  A total of 60 cats (36 Abyssinians, 24 Somalis) were included (37 females, 23 males). For the mutant PK allele, three female Somalis were homozygous (affected, 5%), 17 cats were heterozygous (carrier, 28%) and 40 cats tested negative (normal, 67%). Pedigree analysis revealed common ancestry of affected and many carrier cats. Of affected cats, two had regenerative anaemias and all had reticulocytosis (range 64–390 × 109/L; P < 0.001 compared with normal or carrier cats). The only consistent historical sign was lethargy. One affected cat was euthanased 18 months after testing, because of anaemia, neutropenia, anorexia and weight loss. The mutant allele frequency was 0.19 overall (0.29 in Somalis, 0.13 in Abyssinians). All cats had blood type A. The commercial blood typing card method incorrectly identified 12 cats as having type AB blood.

Conclusions  The frequency of the mutant PK allele is high in Australia. Screening for PK deficiency is indicated before mating and in individual cats of these breeds, even in the absence of anaemia and especially when there is reticulocytosis. Although all cats in the present study had blood type A, blood type B is common in these breeds worldwide. Retyping of any AB typed cats by a laboratory technique is recommended.