bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of oil contamination and cleaning on sea otters (Enhydra lutris), I. Thermoregulatory implications based on pelt studies
Authors: Williams T. M. , Kastelein R. A. , Davis R. W. , Thomas J. A.
Published: January 2009

The contamination of sea otter (Enhydra lutris) fur with crude oil or dispersants reduces its insulation and could subject the animal to hypothermia. This study tested methods for removing crude oil from sea otter pelts, and measured changes in insulation caused by oil contamination and subsequent cleaning. Four detergents and two pretreatments were tested on sea otter pelts soiled with fresh crude, 5-day weathered crude, and an oil–dispersant (COREXIT 9527) solution. To examine the effects of oiling and cleaning on the thermal properties of the fur, the thermal conductance of untreated, oiled, and cleaned pelt samples was determined with a heat-flow transducer. Changes in lipid concentration in the fur resulting from contamination and cleaning were also assessed. The results demonstrated that Dawn dishwashing detergent was the most effective agent in removing crude oil from sea otter fur. This detergent removed similar amounts of oil with 15 or 40 °C rinse water, and was less effective when used in conjunction with mineral oil or soap pretreatments. Oil contamination caused a two- to four-fold increase in thermal conductance over base-line levels (7.64 ± 1.30 W/(m2∙ °C)). Following cleaning, the thermal conductance of the pelt was not significantly different from that of untreated fur. However, mean lipid weight decreased from 7.4 mg lipid/g fur in untreated pelts to 2.0 mg lipid/g fur in cleaned pelts. This study demonstrated that even though natural oils may be lost during the cleaning process, proper cleaning and rinsing restores the water repellency of the sea otter pelt after exposure to crude oil.
Age-related changes in Heligmosomoides polygyrus (Nematoda): neutral lipid content in developing oocytes
Authors: MacKinnon Barbara M. , Lee D. L.
Published: January 2009

Changes in neutral lipid content of developing female gametes in Heligmosomoides polygyrus at 8, 12, 20, 40, 80, and 140 days postinfection (p.i.) were investigated and correlated with egg production by the worms over the same period. Egg production increased to day 20 p.i. when the average egg output for one female reached approximately 700 eggs/day. A decline in egg production occurred from 80 days p.i. until the end of the experiment (140 days p.i.). Neutral lipid content was low in oogonia from worms of all ages. Developing oocytes contained the highest levels of neutral lipid. There was a significant loss of lipid just before fertilization of the oocytes. An increase in lipid occurred in all developmental stages of gametes from day 8 to day 40 p.i., and a significant decline occurred thereafter to day 140 p.i. Although egg production and lipid content of the female reproductive tract showed similar trends, there was not a precise correlation. It is felt that nuclear and cytoplasmic processes other than lipid anabolism or catabolism within the developing gametes play a more important role in influencing egg output.
Comparative morphology of the labrum in Hymenoptera: the digitate labrum of Perilampidae and Eucharitidae (Chalcidoidea)
Authors: Darling D. Christopher
Published: January 2009

The ground plan structure of the labium of the Apocrita and Chalcidoidea was characterized by reference to the structure of the labrum in Symphyta. The ground plan configuration in Chalcidoidea is regarded as flaplike, with many evenly distributed setae and a lobate epipharynx. Within Chalcidoidea, the structure of the labrum was compared in exemplars of Eucharitidae, Perilampidae, and most of the subfamilies currently referred to the Pteromalidae. The digitate labrum of Perilampidae and Eucharitidae is regarded as the first synapomorphy of the two families from the adult stage. The digits of the labrum intermesh with setae of the labiomaxillary complex to form a sievelike apparatus that may exclude pollen and are hypothesized as an adaptation for nectar feeding. The digitate labrum and the flaplike labrum with marginal setae of Chrysolampinae share derived characters: stout setae, reinforced setal bases, and distinct sockets. A transformation series is proposed that derives the digitate labrum from the chrysolampine labrum by the extension of processes from the margin. A survey of the structure of the labrum in Pteromalidae failed to refute this hypothesis of synapomorphy; the labrum of Eutrichosomatinae is similar in many regards but is regarded as independently derived. Three distinct configurations of the labrum are shared by subfamilies and tribes of Pteromalidae: (i) Cleonyminae, Chalcedectinae, Brachyscelidiphaginae, Cerocephalinae, and Macromesinae; (ii) Spalangiinae, Asaphinae, Ceinae, and Miscogasterinae (Ormocerini); and (iii) Miscogasterinae (Sphegigasterini, Miscogasterini) and Pteromalinae. The following subfamilies have unique configurations of the labrum: Chryoslampinae, Diparinae, Eutrichosomatinae, Cratominae, Colotrechninae, and Eunotinae. Hypotheses of transformation of the labrum were suggested for the following: Eutrichosomatinae to Miscogasterinae (Sphegigasterini, Miscogasterini), Pteromalinae; Diparinae to Miscogasterinae (Sphegigasterini, Miscogasterini), Pteromalinae; and Diparinae to Cratominae. The analysis makes explicit use of a priori rules of character transformation as a basis for testable hypotheses of relationships. This method is considered the most appropriate for evaluating complex morphological data sets and should allow progress toward a natural classification in groups, such as the Chalcidoidea, that do not have an explicit phylogenetic hypothesis as a point of departure.
NUMERICAL AND EXPERIMENTAL STUDY OF REGULAR AND CHAOTIC MOTION OF TRIPLE PHYSICAL PENDULUM
Authors: AWREJCEWICZ JAN , SUPEŁ BOGDAN , LAMARQUE CLAUDE-HENRI , KUDRA GRZEGORZ , WASILEWSKI GRZEGORZ , OLEJNIK PAWEŁ
Published: January 2009

Nonlinear dynamics of a real plane and periodically forced triple pendulum is investigated experimentally and numerically. Mathematical modeling includes details, taking into account some characteristic features (for example, real characteristics of joints built by the use of roller bearings) as well as some imperfections (asymmetry of the forcing) of the real system. Parameters of the model are obtained by a combination of the estimation from experimental data and direct measurements of the system's geometric and physical parameters. A few versions of the model of resistance in the joints are tested in the identification process. Good agreement between both numerical simulation results and experimental measurements have been obtained and presented. Some novel features of our real system chaotic dynamics have also been reported, and a novel approach of the rolling bearings friction modeling is proposed, among other.
HOW MANY n-CYCLES DOES PERIOD 3 IMPLY? AN ELEMENTARY APPROACH
Authors: DEL FABBRO CHIARA , GORNI GIANLUCA
Published: January 2009

As is well known, a continuous function f : ℝ → ℝ that has a cycle of period 3 will have cycles of any given period n. Let cn be the minimum of the numbers of distinct cycles of period n, over all possible f with a 3-cycle. We show how cn can be calculated from a simple recursive formula, through elementary and geometrical considerations.
GENERALIZED HÉNON MAPS AND SMALE HORSESHOES OF NEW TYPES
Authors: GONCHENKO SERGEY , LI MING-CHIA , MALKIN MIKHAIL
Published: January 2009

We study hyperbolic dynamics and bifurcations for generalized Hénon maps in the form [Formula: see text] (with b, α small and γ > 4). Hyperbolic horseshoes with alternating orientation, called half-orientable horseshoes, are proved to represent the nonwandering set of the maps in certain parameter regions. We show that there are infinitely many classes of such horseshoes with respect to the local topological conjugacy. We also study transitions from the usual orientable and nonorientable horseshoes to half-orientable ones (and vice versa) as parameters vary.
MODELING AND NONLINEAR DYNAMICAL ANALYSIS OF THE ĆUK CONVERTER UNDER FREE-RUNNING CURRENT-PROGRAMMED CONTROL
Authors: ZHAO YI-BO , WEI DU-QU , LUO XIAO-SHU
Published: January 2009

In this paper, a sliding-mode variable structure model is proposed for studying the nonlinear dynamical behaviors of the free-running current-programmed Ćuk converter. Conditions for the occurrence of various bifurcations are derived analytically, along with simulation results that illustrate the theoretical findings. This paper provides useful information for the stability design of Ćuk converters under free-running current-programmed control and illustrates the application of the nonlinear analysis method to a specific type of plant.
SYNCHRONIZATION IN AN ARRAY OF NONLINEARLY COUPLED CHAOTIC NEURAL NETWORKS WITH DELAY COUPLING
Authors: LU JIANQUAN , HO DANIEL W. C. , CAO JINDE
Published: January 2009

A general complex dynamical network consisting of N nonlinearly coupled identical chaotic neural networks with coupling delays is firstly formulated. Many studied models with coupling systems are special cases of this model. Synchronization in such dynamical network is considered. Based on the Lyapunov–Krasovskii stability theorem, some simple controllers with updated feedback strength are introduced to make the network synchronized. The update gain γi can be properly chosen to make some important nodes synchronized quicker or slower than the rest. Two examples including nearest-neighbor coupled networks and scale-free network are given to verify the validity and effectiveness of the proposed control scheme.
OBSERVER-BASED SYNCHRONIZATION OF UNCERTAIN CHAOTIC SYSTEMS: COMPARISON BETWEEN REDUCED-ORDER AND FULL-ORDER OBSERVERS
Authors: ZHU FANG-LAI , CHEN MAO-YIN
Published: January 2009

Within the drive-response configuration, this paper considers the synchronization of uncertain chaotic systems based on observers. Even if there are unknown disturbances and parameters in the drive system, a robust adaptive full-order observer can be used to realize chaos synchronization. Further, we develop a reduced-order observer-based response system to synchronize the drive system. By choosing a special reduced-order gain matrix, the reduced-order observer-based response system turns out to be linear and can eliminate the influence of the unknown disturbances and parameters directly. We also discuss the above mentioned two kinds of observers in numerical simulation, and demonstrate that the linear reduced-order observer-based response system is better than the full-order observer-based one.
CHAOTIC SYNCHRONIZATION WITH LIMITED INFORMATION
Authors: WANG GEXIA , WANG ZHIMING , LU GUOPING
Published: January 2009

The problem of synchronization of two identically chaotic systems coupled through a limited capacity communication channel (LCCC) is addressed. Using the sampled and encoded information, an impulsive control designed is applied to the response system by resetting its initial state at the beginning of every sampling interval. It is shown that synchronization can be achieved based on the requirement imposed on the number of values taken by the coder, the sampling period and Lipschitz constant of the chaotic system. Based on this requirement, an explicit coder–decoder pair is proposed for chaotic synchronization via a LCCC. Finally, the numerical simulation for the Chua's chaotic system is shown to illustrate the obtained result.
HOPF BIFURCATION AND STABILITY OF PERIODIC SOLUTIONS IN THE DELAYED LIÉNARD EQUATION
Authors: HU GUANG-PING , LI WAN-TONG , YAN XIANG-PING
Published: January 2009

In this paper, the classical Liénard equation with a discrete delay is considered. Under the assumption that the classical Liénard equation without delay has a unique stable trivial equilibrium, we consider the effect of the delay on the stability of zero equilibrium. It is found that the increase of delay not only can change the stability of zero equilibrium but can also lead to the occurrence of periodic solutions near the zero equilibrium. Furthermore, the stability of bifurcated periodic solutions is investigated by applying the normal form theory and center manifold reduction for functional differential equations. Finally, in order to verify these theoretical conclusions, some numerical simulations are given.
BIFURCATION AND CONTROL IN A DIFFERENTIAL-ALGEBRAIC HARVESTED PREY-PREDATOR MODEL WITH STAGE STRUCTURE FOR PREDATOR
Authors: LIU CHAO , ZHANG QINGLING , ZHANG YUE , DUAN XIAODONG
Published: January 2009

A differential-algebraic model system which considers a prey-predator system with stage structure for a predator and a harvest effort on the mature predator is proposed. By using the differential-algebraic system and bifurcation theories, the local stability and instability mechanism of the proposed model system are investigated. With the purpose of stabilizing the proposed model system at the positive equilibrium, a state feedback controller is designed. Finally, a numerical simulation is carried out to show the consistency with theoretical analysis and illustrate the effectiveness of the proposed controller.
INFINITE BASINS OF JULIA SETS
Authors: ÇİLİNGİR FİGEN
Published: January 2009

The goal of this paper is to investigate the iterative behavior of a particular class of rational functions which arise from Newton's method applied to the entire function (z2 + c)eQ(z) where c is a complex parameter and Q is a nonconstant polynomial with deg(Q) ≤ 2. In particular, the basins of attracting fixed points will be described.
GROUP ATTENTION CONTROL FOR COMMUNICATION ROBOTS
Authors: SHIOMI MASAHIRO , KANDA TAKAYUKI , KOIZUMI SATOSHI , ISHIGURO HIROSHI , HAGITA NORIHIRO
Published: January 2009

A humanoid robot can support people in a real environment by interacting with them through human-like body movements, such as shaking hands, greeting, and pointing. In real environments, a robot often interacts with groups of people to provide services, but one-to-many interaction is quite different from one-to-one interaction. For example, a robot cannot satisfy different demands of people simultaneously when it interacts with many people. To solve such problems of interaction, we focused on purpose of attention; it explains why people are aiming their attention in a particular direction. This paper describes a group attention control (GAC) system that enables a communication robot to simultaneously interact with many people. The system is designed to coordinate people's purpose of attention through behavior that is based on two design policies: controlling cooperative situations and indicating explicit control. We implemented a semi-autonomous GAC system in a communication robot that guides visitors to exhibits in a science museum and engages in free-play interactions with them. We developed the semi-autonomous system to concentrate on the behavior-generating mechanism in the GAC system, and to avoid difficulties of sensing problems in real environments. We investigate the effectiveness of the GAC system through a two-week field trial in the museum. Experimental results revealed that visitors evaluated the robot with the GAC system more highly than without it. We believe these results will allow us to develop interactive humanoid robots that can interact effectively with groups of people.
COMPLEXITY IN HUMAN AND HUMANOID BIOMECHANICS
Authors: IVANCEVIC VLADIMIR , SHARMA SANJEEV
Published: January 2009

We propose the following complexity conjecture: in a combined biomechanical system, where the action of Newtonian laws cannot be neglected, it is the mechanical part that determines the lower limit of complexity of the combined system, commonly defined as the number of mechanical degrees of freedom. The biological part of such a system, being "more intelligent", naturally serves as a "controller" for the "nonintelligent" mechanical "plant". Although, in some special cases, the behavior of the combined system might have a "simple" output, a realistic internal state space analysis shows that the total system complexity represents either the superposition, or a kind of "macroscopic entanglement" of the two partial complexities. Neither "mutual canceling" nor "averaging" of the mechanical degrees of freedom generally occurs in such a biomechanical system. The combined system has both dynamical and control complexities. The "realistic" computational model of such a system also has its own computational complexity. We demonstrate the validity of the above conjecture using the example of the physiologically realistic computer model. We further argue that human motion is the simplest well-defined example of a general human behavior, and discuss issues of simplicity versus predictability/controllability in complex systems. Further, we discuss self-assembly in relation to conditioned training in human/humanoid motion. It is argued that there is a significant difference in the observational resolution of human motion while one is watching "subtle" movements of a human hands playing a piano versus "coarse" movements of a human crowd at a football stadium from an orbital satellite. Techniques such as cellular automata can model the coarse crowd motion, but not the subtle hierarchical neural control of the dynamics of human hands playing a piano. Therefore, we propose the observational resolution as a new measure of biomechanical complexity. Finally, there is a possible route to apparent simplicity in biomechanics, in the form of oscillatory synchronization, both external (kinematical) and internal (control).
Anxiety Disorders During Childhood and Adolescence: Origins and Treatment
Authors: Rapee Ronald M. , Schniering Carolyn A. , Hudson Jennifer L.
Published: January 2009

The present review summarizes our current knowledge of the development and management of anxiety in children and adolescents. Consideration is given to limitations of this knowledge and directions for future research. The review begins with coverage of the development and demographic correlates of anxiety in young people and then moves to systematic discussion of some of the key etiological factors, including genetics, temperament, parenting, and individual experiences. The second part of the review describes current treatment strategies and efficacy as well as factors thought to influence treatment outcome, including treatment features, child factors, and parent factors. The review concludes with brief coverage of some more recent developments in treatment including alternative models of delivery and prevention strategies.
Quality-Based Financial Incentives in Health Care: Can We Improve Quality by Paying for It?
Authors: Conrad Douglas A. , Perry Lisa
Published: January 2009

This article asks whether financial incentives can improve the quality of health care. A conceptual framework drawn from microeconomics, agency theory, behavioral economics, and cognitive psychology motivates a set of propositions about incentive effects on clinical quality. These propositions are evaluated through a synthesis of extant peer-reviewed empirical evidence. Comprehensive financial incentives—balancing rewards and penalties; blending structure, process, and outcome measures; emphasizing continuous, absolute performance standards; tailoring the size of incremental rewards to increasing marginal costs of quality improvement; and assuring certainty, frequency, and sustainability of incentive payoffs—offer the prospect of significantly enhancing quality beyond the modest impacts of prevailing pay-for-performance (P4P) programs. Such organizational innovations as the primary care medical home and accountable health care organizations are expected to catalyze more powerful quality incentive models: risk- and quality-adjusted capitation, episode of care payments, and enhanced fee-for-service payments for quality dimensions (e.g., prevention) most amenable to piece-rate delivery.
Social Epidemiology: Social Determinants of Health in the United States: Are We Losing Ground?
Authors: Berkman Lisa F.
Published: January 2009

The United States ranks in the lower tiers of OECD countries in life expectancy, and recent studies indicate that socioeconomic inequalities in health have been widening in the past decades. Over this period, many rigorous longitudinal studies have identified important social, behavioral, and environmental conditions that might reduce health disparities if we could design effective interventions and make specific policy changes to modify them. Often, however, neither our policy changes nor our interventions are as effective as we hoped they would be on the basis of findings from observational studies. Reviewed here are issues related to causal inference and potential explanations for the discrepancy between observational and experimental studies. We conclude that more attention needs to be devoted to (a) identifying the correct etiologic period within a life-course perspective and (b) understanding the dynamic interplay between interventions and the social, economic, and environmental contexts in which interventions are delivered.
Pregnancy-associated thrombotic thrombocytopenic purpura
Authors: Gerth Jens , Schleussner Ekkehard , Kentouche Karim , Busch Martin , Seifert Mandy , Wolf Gunter
Published: January 2009

Thrombocytopenia during pregnancy is a common diagnostic and management problem. Several differential diagnosis must be considered including manifestations of thrombotic thrombocytopenic purpura (TTP). We report here on a case of a 21-year-old pregnant woman who presented initially severe thrombocytopenia (8 Gpt/l) in the 20th+1 week of gestation. The patient had an antibody against ADAMTS13, and enzyme activity was <5%. Immediate plasmapheresis treatment was initiated, followed by plasma infusions, and again plasmapheresis. A male neonate was delivered by caesarean section in the 32nd week of gestation. The child had an uncomplicated postnatal development. After delivery, the mother’s platelet count and ADAMTS13 activity increased to normal values. This case shows interesting aspects of TTP in pregnancy and a close cooperation between obstetricians, nephrologists and pediatricians is necessary for a successful outcome of the pregnancy.
Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies
Authors: Gastoldi Sara , Daina Erica , Belotti Daniela , Pogliani Enrico , Perseghin Paolo , Scalzulli Potito , Paolini Rossella , Marcenò Raimondo , Remuzzi Giuseppe , Galbusera Miriam , Bresin Elena
Published: January 2009

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.
Pathological aspects of membranoproliferative glomerulonephritis (MPGN) and haemolytic uraemic syndrome (HUS) / thrombocytic thrombopenic purpura (TTP)
Authors: Benz Kerstin , Amann Kerstin
Published: January 2009

In this paper, epidemiology, pathogenesis and typical morphological aspects of all three types of membranoproliferative glomerulonephritis (MPGN), of the haemolytic uraemic syndrome (HUS) as well as of thrombotic thrombopenic purpura (TTP) will be reviewed on the light microscopical, immunohistological or immunofluorescence and electron microscopical level. In particular, differences in the pathogenesis of these diseases are discussed. Important recent molecular and genetic insights into the pathogenesis of the three types of MPGN, of typical and atypical HUS and of TTP, i.e. dysregulation of the complement system, distinct molecular defects in C3 and factor H, the major regulatory protein of the alternative pathway of complement activation, and deficiency of a von Willebrand factor (VWF) -cleaving protease, i.e. ADAMTS13, are highlighted. Finally, particular emphasis will be put on differences in glomerular and vascular morphology in the three types of MPGN and in thrombotic microangiopathy (TMA), which is the characteristic morphological alteration of the kidney in HUS and TTP, respectively.
Treatment of PC3 prostate cancer cells with mitoxantrone, etoposide, doxorubicin and carboplatin induces distinct alterations in the expression of kallikreins 5 and 11
Authors: Thomadaki Hellinida , Mavridis Konstantinos , Talieri Maroulio , Scorilas Andreas
Published: January 2009

Several of the novel kallikrein-related peptidases (tissue kallikreins; KLKs) are emerging new serum and/or tissue biomarkers for prostate cancer (CaP) diagnosis, prognosis and monitoring. In the present research approach, our objective was to investigate the possible alterations in the mRNA expression levels of KLK5 and KLK11 genes in prostate cancer cells PC3 as a response to treatment with Mitoxantrone, Etoposide, Doxorubicin and Carboplatin. Viability was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after cell treatment with either mitoxantrone (2 μM), etoposide (20 μM), doxorubicin (1 μM), or carboplatin (15 μM), for 24, 48 and 72 hours. Additionally, trypan blue staining revealed that in PC3 cells all drugs displayed almost the same limited necrotic effects which appeared mainly at 72 hours of treatment. PC3 prostate cancer cells showed a concentration- and time-dependent increased cytotoxicity to the drugs under study which was mainly due to reduction of cell proliferation efficiency. Distinct modulations of KLK5 and KLK11 genes, at the mRNA level, were observed, supporting a drug-dependent cell response. Our experimental data demonstrate that the molecular profile mainly of KLK5 gene may serve as a new potential molecular biomarker predicting treatment response in CaP cells.
Expression analysis and study of KLK4 in benign and malignant breast tumours
Authors: Papachristopoulou Georgia , Avgeris Margaritis , Scorilas Andreas
Published: January 2009

The steroid hormone-regulated gene KLK4 (kallikrein 4) is a new member of the human kallikrein-related peptidase gene family. Up to date, studies report that KLK4 is differentially expressed in many tumours. The purpose of this study was the expression analysis and study of KLK4 in benign and malignant breast tumours. Total RNA was isolated from 16 benign and 45 malignant breast tissue specimens. After testing RNA quality, cDNA was prepared by reverse transcription. Highly sensitive quantitative real-time PCR method for KLK4 mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method 2-ΔΔCT. KLK4 expression was found to vary in both patients’ cohorts; however, a statistically significant elevation of the KLK4 mRNA levels was observed in malignant compared to benign tumour patients. Low KLK4 expression levels were found in well-differentiated tumours (p=0.011) as well as in stage I (p=0.024) patients. Moreover, a statistically significant (rs=-0.318, p=0.035) negative correlation between the KLK4 expression and progesterone receptor staining was observed. ROC and logistic regression analysis recommended that KLK4 gene expression may be used as a new potential biomarker in breast cancer.
Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure
Authors: Budde Ulrich , Kentouche Karim , Sossdorf Maik , Hilberg Thomas , Schneppenheim Reinhart , Reinhart Konrad , Bauer Michael , Brunkhorst Frank , Lösche Wolfgang , Claus Ralf , Bockmeyer Clemens
Published: January 2009

Von Willebrand factor (VWF) and related parameters as well as the protease activity regulating its biological activity were measured in plasma of healthy controls and patients with different cause and severity of systemic inflammation to examine the efficacy of the measures to detect highly prothrombotic states including thrombotic microangiopathy (TMA), one of the sequelae of sepsis. Plasma levels of VWF increased with increasing severity of systemic inflammation, probably due to activation of the endothelium. In parallel, the proteolytic activity of VWF inactivating protease, ADAMTS13, stepwise declined with the severity of inflammation, emphasizing the role of VWF-triggered platelet aggregation on the endothelium subsequently followed by development of TMA. As a consequence, the ratio of VWF antigen level and ADAMTS13 activity was significantly higher in patients with inflammation and sepsis, suggesting that this ratio might be more useful for the diagnosis of highly prothrombotic states including TMA than VWF multimer analysis alone. These findings suggest that ADAMTS13, VWF and related parameters, even in a combined approach, might be useful for the diagnosis and the therapeutic monitoring of patients with sepsis associated thrombotic microangiopathy.
Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients
Authors: Vermeer Cees , Stenger Melanie , Mühlenbruch Georg , Mahnken Andreas , Gladziwa Ulrich , Ketteler Markus , Cranenburg Ellen , Brandenburg Vincent , Schurgers Leon
Published: January 2009

Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 ± 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 ± 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 ± 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = –0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.
The plasma membrane redox system in human platelet functions and platelet-leukocyte interactions
Authors: Frega Gianluca , Savini Isabella , Catani Valeria , Rossi Antonello , Avigliano Luciana , Principe Domenico Del
Published: January 2009

The plasma membrane electron transport is crucial for blood coagulation and thrombosis, since reactive oxygen species and thiol changes, generated by plasma membrane redox reactions, modulate activation of platelets, as well as their interaction with leukocytes. Several antioxidants are linked to this system; thus, platelets are also able to counterbalance radical production and to regulate thrombus growth. Aim of this review is to give an update on the plasma membrane redox system in platelets, as well as on its role in platelet functions and leukocyte-platelet crosstalk.
Shiga toxins, glycosphingolipid diversity, and endothelial cell injury
Authors: Schweppe Christian , Karch Helge , Friedrich Alexander , Müthing Johannes
Published: January 2009

Shiga toxin (Stx)-producing Escherichia coli (STEC) cause an enteric illness that results in a spectrum of outcomes ranging from asymptomatic carriage to uncomplicated diarrhea, bloody diarrhea, and the postdiarrheal haemolytic uremic syndrome (HUS), which leads to renal and other organ microvascular thrombosis. Binding of Stx to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer/CD77) on endothelial cells followed by receptor-mediated endocytosis is the linchpin in STEC-mediated disease. Only GSLs that associate strongly with lipid rafts appear to carry Stxs retrogradely from the plasma membrane through the Golgi apparatus to the endoplasmic reticulum where they are translocated to the cytosol and exert their toxic function. Thus, the biophysical features of the lipid moiety of GSL receptors may influence its incorporation into certain membrane domains and thereby affect toxin destination. Consequently, a detailed structural analysis of Stx-binding GSLs is required to illuminate the molecular causes that may underlie the different Stx susceptibilities of endothelial cells derived from various vascular beds. Solid phase overlay binding assays of thin-layer chromatography (TLC)-separated GSL preparations employing specific antibodies and/or Stxs in conjunction with anti-Stx-antibodies are commonly used for the identification of Stx-binding GSLs. Such GSL-profiling combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) represents a convenient strategy to structurally characterize Stx-receptors from any biological sources such as primary cells, cell lines, or organs. This approach may be helpful to gain insights into Stx-induced impairment of target cells that is suggested to originate at least partly from the structural heterogeneity of the cellular ligands of Stxs.
Autoantibodies in haemolytic uraemic syndrome (HUS)
Authors: Józsi Mihály , Zipfel Peter , Dragon-Durey Marie-Agnes , Fremeaux-Bacchi Veronique , Skerka Christine
Published: January 2009

Haemolytic uraemic syndrome (HUS) is a severe disease with renal failure, microangiopathic anemia and thrombocytopenia. Several mechanisms leading to HUS have been identified, like infections with enterohaemorrhagic Escherichia coli, as well as genetic mutations of complement genes, which result in defective complement control on the surface of host cells. The complement system forms the first defense line of innate immunity and mediates the attack against foreign microorganisms. Defective regulation of this cascade results in attack of self cells and in autoimmune disease. Apparently, the alternative pathway convertase C3bBb is central for the pathophysiology of HUS as gene mutations of the components (C3 and Factor B) or of regulators (Factor H, Factor I and MCP/CD46) are observed in the genetic form of HUS. Recently, a novel mechanism leading to atypical HUS (aHUS) was identified, in form of autoantibodies that bind the complement inhibitor Factor H. Here we summarize the current concept of HUS and focus in particular on the novel subgroup of aHUS patients with IgG autoantibodies to Factor H which develop on the genetic background of CFHR1/CFHR3 deficiency, and which define a new subform termed DEAP-HUS (deficient for CFHR proteins and Factor H autoantibody positive).
Oral anticoagulant therapy in patients with mechanical heart valve and intracranial haemorrhage
Authors: Micieli Evy , Ageno Walter , Squizzato Alessandro , Romualdi Erica
Published: January 2009

Optimal timing for restarting anticoagulant therapy after intracranial bleeding is a critical issue. The purpose of this systematic review is to summarize published studies on the management of oral anticoagulant therapy after intracranial bleeding secondary to the use of vitamin K antagonists in patients with a mechanical heart valve. A computer-assisted search of the MEDLINE and EMBASE electronic databases till January 2008 was performed. Two investigators independently performed study selection and completed a predefined quality assessment and data extraction form. Main inclusion criterion was the enrolment of patients with a mechanical heart valve and intracranial haemorrhage during oral anticoagulant treatment. Any randomised controlled trial, observational cohort study, case series and reports was included. No randomised controlled trials were identified. Six observational cohort studies were included in the final analysis. All studies were of low quality. A total of 120 patients were enrolled. Anticoagulation was restarted within a broad time range (2 days to 3 months). Four ischaemic strokes and two recurrent cerebral haemorrhages occurred after anticoagulation was restarted after a mean follow-up of 7.9 months. Eighteen patients were described in the selected case reports. Anticoagulant therapy was restarted within four days to eight weeks. Two patients had a recurrent haemorrhagic event, and no ischaemic events were reported. In conclusion, restarting oral anticoagulant therapy few days and, indirectly, stopping anticoagulant therapy for a few days (even for 7–14 days) after the occurrence of cerebral haemorrhage are both safe. However, well-designed studies are strongly recommended to provide better evidence.
Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling
Authors: Madonna Rosalinda , Caterina Raffaele De
Published: January 2009

Hyperinsulinemia predicts future cardiovascular events, but may also contribute to atherosclerosis. We therefore studied the consequences of prolonged insulin treatment of human umbilical vein endothelial cells (HUVEC) on the phosphatidylinositol-3‘-kinase(PI3K)/Akt/nitric oxide(NO)-dependent insulin signaling, together with the expression of the pro-atherogenic molecule vascular cell adhesion molecule (VCAM)-1. HUVEC were incubated with insulin (10–11 to 10–7 M) in short- (30 min) and long-term (24 h to 3 days) incubations. In short-term incubations, insulin did not affect constitutive Akt and eNOS at any concentration, but significantly increased their active phosphorylated forms, and NO production. In long-term incubations, however, such insulin effects on the phosphorylated forms, as well as NO production, were attenuated, promoting an effect of insulin also at concentrations otherwise ineffective. Such effects were accompanied by a boosting of insulin effect on VCAM-1 surface expression. In contrast, under similar conditions, insulin did not exert any significant effect on the surface expression of ICAM-1 and E-selectin. Therefore, prolonged exposure of HUVEC to high insulin levels induces a downregulation of the PI3K/Akt/eNOS axis. Such impairment of insulin signalling in states of prolonged hyperinsulinemia pontially contributes to detrimental effects on atherogenesis in insulin resistance states, such as the metabolic syndrome and type 2 diabetes.
Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation
Authors: Steiner Sabine , Seidinger Daniela , Koppensteiner Renate , Gremmel Thomas , Panzer Simon , Kopp Christoph
Published: January 2009

A high on-treatment residual ADP-inducible platelet reactivity in light transmission aggregometry (LTA) has been associated with an increased risk of adverse outcomes after percutaneous coronary intervention (PCI). However, LTA is weakly standardized, and results obtained in one laboratory may not be comparable to those obtained in another one. We therefore sought to determine the test correlating best with LTA to estimate clopidogrel-mediated platelet inhibition in 80 patients on dual antiplatelet therapy after elective percutaneous intervention with stent implantation. We selected the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode platelet aggregometry and the Impact-R for comparisons with LTA. Cut-off values for residual ADP-inducible platelet reactivity were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on the results from LTA. The results from all four assays correlated significantly with those from LTA. The VerifyNow P2Y12 assay revealed the strongest correlation (r = 0.61, p < 0.001). Sensitivities and specificities ranged from 35% to 55%, and from 78.3% to 85%, respectively. In conclusion, although all assays correlated significantly with LTA, they need to be improved to become clinically used diagnostic tests. Further, it may be too early to define the gold standard method for assessing residual ADP-inducible platelet reactivity and generally acceptable cut-off values.
Venous thromboembolism in women using hormonal contraceptives
Authors: Blanco-Molina Ángeles , Trujillo-Santos Javier , Tirado Raimundo , Cañas Inmaculada , Riera Antoni , Valdés Mariano , Monreal Manuel ,   for the RIETE Investigators
Published: January 2009

There is scarce information on the clinical characteristics of contraceptive users who develop venous thromboembolism (VTE). RIETE is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We analyzed the clinical characteristics and additional risk factors for VTE in all enrolled women aged <50 years who were using or not using contraceptives at presentation with VTE. Of 1,667 women aged <50 years enrolled in RIETE as of December 2007, 593 (36%) were contraceptive users. Of 270 aged <25 years, 190 (70%) were users. Ninety-two contraceptive users (16%) had over-weight, 89 (15%) were obese. Of 951 women with no additional risk factors for VTE (i.e. recent surgery, immobility or cancer) 457 (48%) were contraceptive users. Eighty-seven (15%) users had recent immobility for ≥4 days, 44 (7.4%) were postoperative. The most common reason for immobility was lower limb trauma not requiring surgery; 25% of users with recent immobility had received thromboprophylaxis. The most common type of surgery was non-major orthopaedic surgery. Twenty-one (48%) users with postoperative VTE had received prophylaxis. The percentage of users and non-users who tested positive for thrombophilia was similar. Contraceptive use remains the most frequent risk factor for VTE in women at fertile age. Identifying those at increased risk for VTE seems to be difficult. In the meanwhile, a higher use of thromboprophylaxis during immobility or minor surgery should be warranted.
Bridging North and South: Inquisitorial Networks and Witchcraft Theory on the Eve of the Reformation
Authors: Herzig Tamar
Published: January 2009

This article reconstructs a network of Dominican inquisitors who facilitated the reception and adaptation of northern European demonological notions in the Italian peninsula. It focuses on the collaboration of Italian friars with Heinrich Kramer, the infamous Alsatian witch-hunter and author of the Malleus Maleficarum (1486). Drawing on newly-discovered archival sources as well as on published works from the early sixteenth century, it proposes that Italian inquisitors provided Kramer with information on local saintly figures and were, in turn, influenced by his views on witchcraft. Following their encounter with Kramer in 1499-1500, they came to regard witches as members of an organized diabolical sect, and were largely responsible for turning the Malleus into the focal point of the Italian debate over witch-hunting. I argue that Kramer's case attests to the important role of papal inquisitors before the Reformation in bridging the cultural and religious worlds south and north of the Alps.
Bollène-2002 Experiment: Radar Quantitative Precipitation Estimation in the Cévennes–Vivarais Region, France
Authors: Delrieu Guy , Boudevillain Brice , Nicol John , Chapon Benoît , Kirstetter Pierre-Emmanuel , Andrieu Hervé , Faure D.
Published: January 2009

The Bollène-2002 Experiment was aimed at developing the use of a radar volume-scanning strategy for conducting radar rainfall estimations in the mountainous regions of France. A developmental radar processing system, called Traitements Régionalisés et Adaptatifs de Données Radar pour l’Hydrologie (Regionalized and Adaptive Radar Data Processing for Hydrological Applications), has been built and several algorithms were specifically produced as part of this project. These algorithms include 1) a clutter identification technique based on the pulse-to-pulse variability of reflectivity Z for noncoherent radar, 2) a coupled procedure for determining a rain partition between convective and widespread rainfall R and the associated normalized vertical profiles of reflectivity, and 3) a method for calculating reflectivity at ground level from reflectivities measured aloft. Several radar processing strategies, including nonadaptive, time-adaptive, and space–time-adaptive variants, have been implemented to assess the performance of these new algorithms. Reference rainfall data were derived from a careful analysis of rain gauge datasets furnished by the Cévennes–Vivarais Mediterranean Hydrometeorological Observatory. The assessment criteria for five intense and long-lasting Mediterranean rain events have proven that good quantitative precipitation estimates can be obtained from radar data alone within 100-km range by using well-sited, well-maintained radar systems and sophisticated, physically based data-processing systems. The basic requirements entail performing accurate electronic calibration and stability verification, determining the radar detection domain, achieving efficient clutter elimination, and capturing the vertical structure(s) of reflectivity for the target event. Radar performance was shown to depend on type of rainfall, with better results obtained with deep convective rain systems (Nash coefficients of roughly 0.90 for point radar–rain gauge comparisons at the event time step), as opposed to shallow convective and frontal rain systems (Nash coefficients in the 0.6–0.8 range). In comparison with time-adaptive strategies, the space–time-adaptive strategy yields a very significant reduction in the radar–rain gauge bias while the level of scatter remains basically unchanged. Because the Z–R relationships have not been optimized in this study, results are attributed to an improved processing of spatial variations in the vertical profile of reflectivity. The two main recommendations for future work consist of adapting the rain separation method for radar network operations and documenting Z–R relationships conditional on rainfall type.