bluuebunny/crossref_metadata_2025 huggingface dataset:
Inventing the "Mulher Paulista": Politics, Rebellion, and the Gendering of Brazilian Regional Identities
Authors: Weinstein Barbara
Published: March 2006

This article considers the complicated relationship between women's mobilization and their recognition as political actors. In 1932 the state of São Paulo, long Brazil's dominant political center, took up arms against the federal government, headed by Getúlio Vargas, in protest against São Paulo's diminished status under the new dictatorship. A key feature of this short-lived civil war was the prominent role of women in the regionalist movement. Contemporary accounts emphasized the active participation of women—testimony that implies an expanded female presence in the public sphere. I argue, however, that identification of the movement's female supporters with an archetypical figure, A Mulher Paulista (The Paulista Woman) limited the subversive implications of women's mobilization. Far from celebrating women's new role in politics, women and men involved in the movement construed women's participation as exceptional and motivated by moral outrage, not politics. Furthermore, the figure of A Mulher Paulista had a specific class and racial valence; the paulista leadership represented her participation as emblematic of the modernity and civic superiority of regional culture, compared to the poorer, less Europeanized regions of Brazil that supported the dictatorship.
Interface Design, Web Portals, and Children
Authors: Large J. A , Beheshti Jamshid
Published: March 2006

Children seek information in order to complete school projects on a wide variety of topics, as well as to support their various leisure activities. Such information can be found in print documents, but increasingly young people are turning to the Web to meet their information needs. In order to exploit this resource, however, children must be able to search or browse digital information through the intermediation of an interface. In particular, they must use Web-based portals that in most cases have been designed for adult users. Guidelines for interface design are not hard to find, but typically they also postulate adult rather than juvenile users. The authors discuss their own research work that has focused upon what young people themselves have to say about the design of portal interfaces. They conclude that specific interface design guidelines are required for young users rather than simply relying upon general design guidelines, and that in order to formulate such guidelines it is necessary to actively include the young people themselves in this process.
Initial Findings from a Three-Year International Case Study Exploring Children's Responses to Literature in a Digital Library
Authors: Massey Sheri , Weeks Ann Carlson , Druin Allison
Published: March 2006

This article examines children's responses to self-selected books in a digital library and begins to identify patterns in those responses. As part of a larger longitudinal study, the study presented here is an analysis of 241 book response forms submitted by 12 children from 4 countries: Germany, Honduras, New Zealand, and the United States. The children described most of the books they read as being funny or happy and generally rated them with four or five stars (out of five stars). The most commonly identified types of responses were those expressing like or dislike, summarizing the text, or explaining how the book made the child feel. Two factors were identified that influenced response patterns from the study sites: the data collection instrument and adult mediation. This research has implications for library program development related to recreational reading and for changes in the procedures for data collection in this area of research.
Teens Are from Neptune, Librarians Are from Pluto: An Analysis of Online Reference Transactions
Authors: Walter Virginia A , Mediavilla Cindy
Published: March 2006

As part of a project to evaluate the effectiveness of Tutor.com's Live Homework Help service, the authors examined over 100 transcripts of online transactions between teens and the virtual reference librarians in California who connect students to Live Homework Help tutors. Using content analysis, the authors document and discuss the difference in online communication styles between teens and adults. In addition, the transactions are measured against Reference and User Services Association's (RUSA) reference performance guidelines and are found to be severely lacking in the qualities required for effective reference service. Recommendations are made within the context of positive library service to young adults, including recommendations on how to make virtual reference encounters with teens more responsive to their homework needs.
Democracy and Economic Growth: A Historical Perspective
Authors: Gerring John , Bond Philip , Barndt William T. , Moreno Carola
Published: March 2006

Recent studies appear to show that democracy has no robust association with economic growth. Yet all such work assumes that the causal effect of democracy can be measured by a country's regime status in a particular year (T), which is correlated with its growth performance in a subsequent period (T+l). The authors argue that democracy must be understood as astock,rather than alevel,measure. That is, a country's growth performance is affected by the number of years it has been democratic, in addition to the degree of democracy experienced during that period. In this fashion, democracy is reconceptualized as a historical, rather than a contemporary, variable—with the assumption that long-run historical patterns may help scholars to understand present trends. The authors speculate that these secular-historical influences operate through four causal pathways, each of which may be understood as a type of capital: physical capital, human capital, social capital, and political capital. This argument is tested in a crosscountry analysis and is shown to be robust in a wide variety of specifications and formats.
Die Diagnostik der Toxocara-Infestationen und der Toxokarose des Menschen The diagnosis of Toxocara infestations and of human toxocarosis
Authors: Auer Herbert , Aspöck Horst
Published: March 2006

Die beiden Askariden-Spezies Toxocara canis (Hundespulwurm) und T. cati (Katzenspulwurm) leben als Adulte im Dünndarm von Hund und Fuchs bzw. der Katze. Durch orale Aufnahme infektionstüchtiger Toxocara-Eier aus den Fäzes von Hund, Fuchs und Katze kann auch der Mensch die Infektion erwerben. Die im Dünndarm des Menschen schlüpfenden Wurmlarven können über den Pfortaderkreislauf, über Herz, Lunge und den großen Blutkreislauf in alle Organe des Menschen gelangen. In den meisten Fällen verläuft die Infestation klinisch inapparent oder subklinisch, in anderen Fällen kann es zu klinischen Manifestationen sehr unterschiedlicher Art kommen: Larva migrans visceralis-Syndrom (VLM), okuläres Larva migrans-Syndrom (OLM), inapparente Toxokarose, gemeine Toxokarose, zerebrale Toxokarose.

Die Laboratoriumsdiagnostik der Toxocara-Infestationen basiert auf dem Nachweis spezifischer Antikörper mittels ELISA und Western Blot, doch stehen zudem auch Verfahren zum Nachweis von zirkulierendem Antigen oder Antigen in situ zur Verfügung. Die PCR hat in der Routinediagnostik (noch?) keine Bedeutung.

Die Vielfalt der durch Toxocara-Larven ausgelösten Symptome ist Anlass, diese Helminthose bei einer Vielzahl von Krankheitsbildern unklarer Genese differentialdiagnostisch einzubeziehen.

Der ausführlichen Darstellung der laboratoriums-diagnostischen Methoden wird ein kurzer Überblick über Biologie, Vorkommen und Häufigkeit der Erreger, Pathogenese und Klinik sowie über die Möglichkeiten der Therapie vorangestellt. Hinweise auf andere Askariden-Arten, die beim Menschen ähnliche Erkrankungen auslösen können, ergänzen diese Übersicht.
Das Respiratory Syncytial Virus (RSV): Epidemiologie, Klinik und Labordiagnose Respiratory Syncytial Virus (RSV): epidemiology, clinical manifestations and laboratory diagnosis
Authors: Allwinn Regina , Weber Bernard
Published: March 2006

Infektionen mit dem Respiratory Syncytial Virus (RSV) sind weltweit die bedeutendsten Atemwegserkrankungen im Säuglings- und Kindesalter. Die RS-Viren werden durch Schmierinfektionen und Aerosole übertragen, der Mensch ist das einzige Erregerreservoir. Im Säuglings- und Kleinkindalter finden gehäuft RSV-Infektionen statt. Mit zwei Jahren sind bereits 95% der Kinder seropositiv. Maternale Antikörper gewährleisten im Säuglingsalter keinen ausreichenden Nestschutz. Es ist von keiner sicheren Immunität auszugehen, daher sind Reinfektionen die Regel. Der Häufigkeitsgipfel der RSV-Infektionen liegt in den Winter- und Frühlingsmonaten. Frühgeborene, immundefiziente und immunsupprimierte Patienten können das Virus mehrere Wochen ausscheiden. RSV-Infektionen verursachen zumeist Bronchitis, Bronchiolitis oder Pneumonie. Die Methode der Wahl ist der Erregernachweis über eine Virusisolierung in der Zellkultur im akuten Erkrankungsfall. Benötigt wird Nasenspülwasser oder ein tiefer Rachenabstrich. Auf einen schnellen Transport unter gekühlten Bedingungen ist zu achten (4°C). Die Antikörpernachweise (Serologie) sind die Methode der Wahl für die epidemiologischen Auswertungen und weniger für die Akutdiagnostik geeignet. Nach dem Infektionsschutzgesetz (IfSG) § 6 Abs. 3 sind dem Gesundheitsamt gehäuft auftretende RSV-Infektionen zu melden. Die Therapie erfolgt symptomatisch; in schweren Fällen kann Ribavirin als Aerosol eingesetzt werden. Eine passive Immunisierung mit humanen Antikörpern gegen RSV kann bei Kindern mit erhöhtem Infektionsrisiko i.v. verabreicht werden (RespiGam). Auch sind monoklonale Antikörper gegen RSV (Palivizumab) prophylaktisch wirksam.
Host factors and disease severity in two patients with SARS Wirtsfaktoren und Erkrankungsschwere bei zwei Patienten mit SARS
Authors: Rickerts Volker , Reinhard Brodt Hans , Schneider Bernd , Weidmann Eckhart , Uwe Chow Kai
Published: March 2006

Infection with the SARS (Severe Acute Respiratory Syndrome)-associated coronavirus results in respiratory failure probably by immunological mechanisms in 10% of patients. Laboratory markers that predict subsequent respiratory failure would therefore be useful in patient management.

We describe the clinical course, hematologic parameters, lymphocyte subpopulations and markers of inflammation in two patients with SARS, i.e., one man with diabetes mellitus and one pregnant woman, infected by the same viral isolate.

The patient with underlying diabetes mellitus developed respiratory failure after admission in the second week of the illness while the second patient developed only a mild disease without respiratory failure. Subsequent respiratory dysfunction was associated with low numbers of Natural Killer (NK) cells at presentation and elevated CRP levels during the illness.

NK cells and CRP levels at the end of the first week of the disease might be related to subsequent respiratory dysfunction and may link underlying conditions to disease severity.
A pediatric perspective on hemochromatosis: not just “an old man's disease” Eine pädiatrische Sichtweise der Hämochromatosis: nicht nur ein Altersleiden
Authors: Lockitch Gillian , Litvinova Mariya M.
Published: March 2006

Hemochromatosis, once considered to be an autosomal recessive disorder of increased iron absorption, predominantly affecting men after the fourth decade of life, is now known to be a syndrome caused by mutations in at least five different genes, one of which results in an autosomal dominant form of the disease. The most severe form, known as juvenile hemochromatosis, is seen in individuals less than thirty years of age and has been described in a child as young as four years. The pediatric significance of hemochromatosis is discussed.
Prothrombin time with citrated capillary whole blood as sample on a STA®Analyzer Bestimmung der Prothrombinzeit aus Kapillar-Citratblut am STA®-Analyzer
Authors: Albrecht Joachim , Brehmer Chris , Reichert Heike
Published: March 2006

In many doctors' offices for which our laboratory analyzes samples, citrated capillary whole blood (CCWB) is the preferred sample material for International Normalized Ratio (INR) testing for patients under oral anticoagulation therapy (OAC). In order to handle the workload efficiently, we adapted and validated the Owrens prothrombin time determination (STA® Hepato Quick) for this type of sample on our STA® Coagulation Analyzer. We found that the red blood cells, platelets etc. do not affect the clotting reaction itself, and the variance due to sedimentation of these cells while the sample is waiting on-board the instrument can be ignored for up to 30 min at least. The clotting times (CT) with CCWB are approximately 15% shorter compared to those of diluted citrated plasma (CP). When these shorter CTs are corrected for, the precalibration curve for CP provided by the manufacturer can also be used for CCWB. Based on the data obtained with five different lots of reagent we were able to calculate and validate a single factor (0.874). The international sensitivity indexes (ISI) for CP and CCWB were identical, in agreement with the literature [1]. To demonstrate lot independence, we applied the factor to data obtained with a sixth lot. CP and CCWB gave identical INR results.
Full-field Laser Shearography Instrumentation for the Detection and Characterization of Fatigue Cracks in Titanium 10-2-3
Authors: Groves RM , Furfari D , Barnes SE , James SW , Fu S , Irving PE , Tatam RP
Published: March 2006

A multi-component shearography instrument is used to investigate the in-plane surface strain fields in titanium 10-2-3 alloy specimens subjected to tensile loads. Titanium 10-2-3 alloy samples containing fatigue cracks with lengths from 0.7 to 5 mm were investigated using the shearography instrumentation. In-plane and out-of-plane measurements of surface strain are presented, along with comparative data from resistance strain gages. Factors determining the detection sensitivity, the limit of detection for crack lengths, and the accuracy of the strain field were established.
Sensitivity Analysis and Neutron Fluence Adjustment for VVER-440 RPV
Authors: Belousov SI , Ilieva KD , Matushko VL
Published: March 2006

Adjustment of the neutron fluence on the VVER-440 reactor pressure vessel (RPV) inner wall has been carried out. For the purpose of this adjustment the neutron flux responses' sensitivity to the main parameters of calculation uncertainty has been calculated. The obtained sensitivities, the parameters uncertainty, and activity measurement data of iron, copper, and niobium detectors positioned behind the RPV of Kozloduy NPP Unit 1 have been used in this adjustment.
The Oxygen Index of Surgical Drape Materials
Authors: Serrao GW , Micou MK , Sidebotham GW , Wolf GL
Published: March 2006

An effective method for minimizing operating room fires is to use materials that are least flammable in air and in oxygen-enriched atmospheres (OEA). The objective of this study was to characterize the flammability of commonly used surgical drapes by measuring the minimum concentration of oxygen [O2] required to support a candle-like flame on the test specimen, the oxygen index (OI) [1]. Under the conditions studied, the OI was 17.8 for woven cotton towels (Huck), 18.5 for nonwoven cellulose draping, and 22.8 for polypropylene draping. These data demonstrate that materials commonly used for surgical draping have an OI less than or near the O2 content of ambient air (21 %), making them particularly susceptible to fire in the localized OEA of the operating room. Quantitative measures, such as the OI, are useful for determining the relative flammability of materials and their consideration should play an important role in optimizing operating room safety.
High Frequency Dynamic Testing of Rubbers and Rubber to Metal Devices
Authors: Cambiaghi D , Magalini A , Ramorino G , Riccò T , Vetturi D
Published: March 2006

This paper develops a methodology to test and evaluate the dynamic properties of elastomeric compounds and of rubber to metal devices by means of an electrodynamic shaker. The dynamic tensile and shear moduli of elastomeric materials and the dynamic stiffness of rubber components are evaluated under different conditions of excitation frequency, temperature, dynamic deformation, and static load.
Evaluation of the ASTMJInitiation Procedure Using the EURO Fracture Toughness Data Set
Authors: Landes JD
Published: March 2006

The multiple specimen procedure for the evaluation of a JIc value as presently measured using ASTM E 1820 is examined using the large fracture toughness dataset from the EURO round robin. Although a standard test procedure for JIc determination has been in use for more than 20 years, the multiple specimen option has not been regularly reassessed during that time. The EURO dataset was generated to evaluate the transition fracture toughness methods for steels. However, many of the test results produced ductile fracture information in terms of a final J versus ductile crack extension. This is the same information that is measured in a multiple specimen J initiation fracture toughness test. The dataset has more than 300 individual points of J versus crack extension and may be the largest dataset of that type produced for one material. Therefore, it is a useful dataset for evaluating the multiple specimen JIc procedure in ASTM E 1820. This evaluation showed that a value of JIc cannot be determined for a dataset containing more than 300 points, even though these points gave a consistent J-R curve. The criteria that are used for qualification of the data eliminate all of the points as being not qualified. This raises some serious concerns about the usefulness of the method as it is presently written, especially the restrictive nature of the qualification rules. Individual qualification criteria are examined and recommendations made for developing a more reasonable test method, one that can be used in the future to evaluate a multiple specimen fracture toughness for materials typically used in structural applications.
Relationship between Habitat and Sport Fish Populations over a 20-Year Period at West Lake Tohopekaliga, Florida
Authors: Bonvechio Kimberly I. , Bonvechio Timothy F.
Published: March 2006

Relationships between environmental variables and sport fish population parameters were investigated for West Lake Tohopekaliga from 1983 to 2002. Through time, the lake has undergone a process of cultural oligotrophication as indicated by reductions in nutrient and chlorophyll-a concentrations because of improvements in wastewater treatment and the establishment of hydrilla Hydrilla verticillata in the system. With this decline in trophic state, angler catch and catch rate increased for largemouth bass Micropterus salmoides, but harvest and harvest rate decreased for black crappie Pomoxis nigromaculatus. Furthermore, the angler base of the lake shifted almost exclusively to those fishing for largemouth bass. Although angling effort for largemouth bass has increased through time with reductions in trophic state, angling effort for black crappies and sunfish species Lepomis spp. has declined. The growth of largemouth bass less than age 5 has also declined since the late 1980s, and the proportion of memorable-sized fish in electrofishing catches decreased with decreases in total phosphorus. Areal coverage of hydrilla varied dramatically throughout this 20-year period, and angler catch rate of largemouth bass as well as angler harvest rate of black crappies were positively correlated with hydrilla coverage. We believe the current level of nutrients and intermediate levels of vegetation (20–40%) should be maintained to balance the needs of both the angling and nonangling communities and to maximize the economic potential of the lake.
The influence of talking on showing and telling: adult‐child talk and children's verbal and nonverbal event recall
Authors: McGuigan Fiona , Salmon Karen
Published: March 2006

Although adult–child discussion during an event has been shown to influence children's verbal recall, limited research has investigated its influence on nonverbal recall, particularly in the early school years. The current experiment addressed this gap. Sixty‐five 5‐ to 6‐year old children participated in a staged, novel event and were interviewed about it 2 weeks later. The 4 experimental conditions varied as to whether the children experiencedemptyorelaborativeadult–child talk during the event and whether, during the memory interview, verbal recall preceded re‐enactment (verbal‐first) or re‐enactment preceded verbal recall (nonverbal‐first). Replicating previous findings, elaborative talk increased the correct information in verbal recall. Moreover, elaborative talk increased the amount and accuracy of the information re‐enacted and reduced the errors made. Interview order did not influence the results. The findings extend theory and research by demonstrating that by age 5 years, elaborative talk influences not only verbal but also nonverbal recall. Copyright © 2006 John Wiley & Sons, Ltd.
Assessment of sensory substitution prosthesis potentialities in minimalist conditions of learning
Authors: Poirier Colline , Richard Marie‐Annick , Duy Dai Tran , Veraart Claude
Published: March 2006

Pattern recognition with a prosthesis substituting vision by audition was investigated. During 15 1‐hour sessions, nine blindfolded sighted subjects were trained to recognise 2D patterns by trial and error. In addition to a global assessment, recognition of pattern element nature (vertical bars, horizontal bars…), element size and element spatial arrangement were independently assessed for each pattern. Influence of experimental parameters (complexity level of patterns, exploration number of a pattern) on recognition was studied. Performances improved over sessions. As a rule, patterns element nature was less well recognised than element size and spatial arrangement. Experimental parameters influenced pattern recognition performance. Results are discussed in relation with auditory and visual perception as well as in the perspective to implement a learning protocol for future users of prosthesis. Copyright © 2006 John Wiley & Sons, Ltd.
Cover Picture: Artemisone—A Highly Active Antimalarial Drug of the Artemisinin Class (Angew. Chem. Int. Ed. 13/2006)
Authors: Haynes Richard K. , Fugmann Burkhard , Stetter Jörg , Rieckmann Karl , Heilmann Hans‐Dietrich , Chan Ho‐Wai , Cheung Man‐Ki , Lam Wai‐Lun , Wong Ho‐Ning , Croft Simon L. , Vivas Livia , Rattray Lauren , Stewart Lindsay , Peters Wallace , Robinson Brian L. , Edstein Michael D. , Kotecka Barbara , Kyle Dennis E. , Beckermann Bernhard , Gerisch Michael , Radtke Martin , Schmuck Gabriele , Steinke Wolfram , Wollborn Ute , Schmeer Karl , Römer Axel
Published: March 2006

Qing hao su, or artemisinin, is the active compound isolated from the herb Artemisia annua (qīng hāo) shown in the cover picture. The Chinese text shown describing its use in Chinese medicine dates back to 340 AD. Derivatives of artemisinin are currently used for the treatment of malaria. In their Communication on page 2082 ff., R. K. Haynes et al. describe the preparation and superior efficacy of the new derivative artemisone against the malaria parasite. (Chinese text verified by Prof. Chun‐Tao Che.)
Maturational opportunities in migration: separation–individuation perspective
Authors: Mirsky Julia , Peretz Yael
Published: March 2006

The psychological research of migration tends to overstress its distress‐provoking aspects and neglect the psychological opportunities that immigration presents. Based on the conceptualization of migration as a separation–individuation process, this paper attempts to shed some light on potential growth‐promoting factors in migration. Through the narrative of a young woman immigrant, it demonstrates how migration may offer an additional opportunity for psychological maturation and the attainment of autonomy. Copyright © 2006 John Wiley & Sons, Ltd.
The pathogenesis of greed: causes and consequences
Authors: Nikelly Arthur
Published: March 2006

The passion for selfish gratification in the amassing of wealth, and the worship of money through fraudulent and deceptive tactics, have become an increasingly visible and widely destructive phenomenon in society. This essay explores the nature, etiology, and impact of runaway greed on mental and physical health, and on the society and the environment. It examines the historical and metaphorical meanings of greed and its identification with social, cultural, religious, and economic determinants. The psychoanalytic explanation of acquisitive behavior is described along with approaches to treatment. The purpose of this analysis is to stimulate interest in the study of acquisitiveness and to raise awareness of its insidious consequences on the self and on society. Copyright © 2006 John Wiley & Sons, Ltd.
Enhanced molecular recognition signal in allosteric biosensing by proper substrate selection
Authors: Ferraz Rosa María , Arís Anna , Villaverde Antonio
Published: March 2006

Among protein biosensors, those based on enzymatic responses to specific analytes offer convenient instruments for fast and ultra‐fast molecular diagnosis, through the comparative analysis of the product formed in presence and in absence of the effector. We have explored here the performance of five β‐galactosidase substrates during the activation of a β‐galactosidase sensor by antibodies against the human immunodeficiency virus (HIV). Interestingly, the employed substrate determines the dynamic range of the allosteric signal and significantly influences the sensitivity of the senso‐enzymatic reaction. While ortho‐nitrophenyl β‐D‐galactopyranoside allows the detection of a model anti‐gp41 monoclonal antibody below 0.024 ng/µL, phenol red β‐D‐galactopyranoside offers the most dynamic response with signal/background ratios higher than 12‐fold and a detection limit around 0.071 ng/µL. The hydrolysis of both chromogenic substrates generates linear sensing responses to immune human sera and parallel time‐course topologies of the allosteric reaction. Therefore, the obtained results stress the potential of chromogenic substrates versus those rendering quimioluminescent, amperometric, or fluorescent signals, for the further automatization, miniaturization, or adaptation of β‐galactosidase‐based biosensing to high‐throughput applications. © 2006 Wiley Periodicals, Inc.
Thermal inactivation of D‐amino acid oxidase from Trigonopsis variabilis occurs via three parallel paths of irreversible denaturation
Authors: Dib Iskandar , Slavica Anita , Riethorst Waander , Nidetzky Bernd
Published: March 2006

Trigonopsis variabilis D‐amino acid oxidase (TvDAO) is a long‐known flavoenzyme whose most important biocatalytic application is currently the industrial production of 7‐amino‐cephalosporanic acid (7‐ACA) from cephalosporin C. Lacking mechanistic foundation, rational stabilization of TvDAO for improved process performance remains a problem. We report on results of thermal denaturation studies at 50°C in which two purified TvDAO forms were compared: the native enzyme, and a site‐specifically oxidized protein variant that had the side chain of cysteine108 converted into a sulfinic acid and lost 75% of original specific activity. Although inactivation time courses for both enzymes are fairly well described by simple single‐exponential decays, the underlying denaturation mechanisms are shown by experiments and modeling to be complex. One main path leading to inactivation is FAD release, a process whose net rate is determined by the reverse association rate constant (k), which is 25‐fold lower in the oxidized form of TvDAO. Cofactor dissociation is kinetically coupled to aggregation and can be blocked completely by the addition of free FAD. Aggregation is markedly attenuated in the less stable Cys108‐SO2H‐containing enzyme, suggesting that it is a step accompanying but not causing the inactivation. A second parallel path, characterized by a k‐value of 0.26/h that is not dependent on protein concentration and identical for both enzymes, likely reflects thermal unfolding reactions. A third, however, slow process is the conversion of the native enzyme into the oxidized form (k < 0.03/h). The results fully explain the different stabilities of native and oxidized TvDAO and provide an inactivation mechanism‐based tool for the stabilization of the soluble oxidase. © 2006 Wiley Periodicals, Inc.
Dynamic Structural Investigations on the Torpedo Nicotinic Acetylcholine Receptor by Time‐Resolved Photoaffinity Labeling
Authors: Mourot Alexandre , Grutter Thomas , Goeldner Maurice , Kotzyba‐Hibert Florence
Published: March 2006

An increasing number of high‐resolution structures of membrane‐embedded ion channels (or soluble homologues) have emerged during the last couple of years. The most pressing need now is to understand the complex mechanism underlying ion‐channel function. Time‐resolved photoaffinity labeling is a suitable tool for investigating the molecular function of membrane proteins, especially when high‐resolution structures of related proteins are available. However until now this methodology has only been used on the Torpedo nicotinic acetylcholine receptor (nAChR). nAChRs are allosteric cation‐selective receptor channels that are activated by the neurotransmitter acetylcholine (ACh) and implicated in numerous physiological and pathological processes. Time‐resolved photoaffinity labeling has already enabled local motions of nAChR subdomains (i.e. agonist binding sites, ion channel, subunit interface) to be understood at the molecular level, and has helped to explain how small molecules can exert their physiological effect, an important step toward the development of drug design. Recent analytical and technical improvements should allow the application of this powerful methodology to other membrane proteins in the near future.
Real‐time MRI guided atrial septal puncture and balloon septostomy in swine
Authors: Raval Amish N. , Karmarkar Parag V. , Guttman Michael A. , Ozturk Cengizhan , DeSilva Ranil , Aviles Ronnier J. , Wright Victor J. , Schenke William H. , Atalar Ergin , McVeigh Elliot R. , Lederman Robert J.
Published: March 2006

Cardiac perforation during atrial septal puncture (ASP) might be avoided by improved image guidance. X‐ray fluoroscopy (XRF), which guides ASP, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real‐time MRI (rtMRI) provides excellent tissue contrast in any orientation and may enable ASP and balloon atrial septostomy (BAS) in swine. Custom MRI catheters incorporated “active” (receiver antenna) and “passive” (iron or gadolinium) elements. Wholly rtMRI‐guided transfemoral ASP and BAS were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded MRI. Successful ASP was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. BAS was successful in 9/10 animals. Antenna failure in a re‐used needle led to inadvertent vena cava tear prior to BAS in 1 animal. ASP in the same animal was easily performed using a new needle. rtMRI illustrated clear device‐tissue‐lumen relationships in multiple orientations, and facilitated simple ASP and BAS. The mean procedure time was 19 ± 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals. Interactive rtMRI permits rapid transcatheter ASP and BAS in swine. Further technical development may enable novel applications. Published 2006 Wiley‐Liss, Inc.
Coil embolization of a circumflex coronary aneurysm at the time of percutaneous coronary stenting
Authors: Kereiakes Dean J. , Long Dan E. , Ivey Thomas D.
Published: March 2006

Coronary atherosclerotic aneurysm often occurs in association with severe atherosclerotic coronary stenosis. We describe the percutaneous catheter‐based approach to coil embolization of a circumflex coronary aneurysm at the time of obtuse marginal branch coronary stent deployment. © 2006 Wiley‐Liss, Inc.
Safety and efficacy of staple‐mediated femoral arteriotomy closure: Results from a randomized multicenter study
Authors: Ansel Gary , Yakubov Stephen , Neilsen Christopher , Allie David , Stoler Robert , Hall Patrick , Fail Peter , Sanborn Timothy , Caputo Ronald P.
Published: March 2006

Background:

Mechanical closure of percutaneous femoral arteriotomies following catheter based procedures remains problematic.

Methods:

The EVS closure device is the first to utilize a staple to effect arteriotomy closure and was compared to manual compression following sheath removal in a 362 patient randomized (2:1 to device) multicenter trial. As pre‐specified, one half of the patients underwent coronary intervention.

Results:

Time to hemostasis was significantly reduced in the EVS group for both diagnostic (3.3 ± 2.6 vs. 19.3 ± 5.7 minutes; p < 0.001) and interventional procedures (5.5 ± 5.1 vs. 22.3 ± 9.9 minutes; p < 0.0001). Time to ambulation was similarly reduced in the EVS group following diagnostic (2.4 ± 3.3 vs. 6.0 ± 5.2 hours; p < 0.001) and interventional procedures (3.4 ± 4.5 vs. 7.6 ± 7.0 hours; p < 0.001). The incidence of major complications was similar between the EVS and manual compression groups at discharge (0.4% vs. 1.7%; p = NS) and at 30 day follow‐up (0.4% vs. 2.5%; p = NS).

Conclusion:

Compared to manual compression, the EVS device provides a safe and effective method of femoral artery closure. © 2006 Wiley‐Liss, Inc.
Time‐resolved circular dichroism in carbonmonoxy‐myoglobin: The central role of the proximal histidine
Authors: Dartigalongue Thibault , Hache François
Published: March 2006

A calculation of the circular dichroism (CD) spectra of carbonmonoxy‐ and deoxy‐myoglobin is carried out in relation to a time‐resolved CD experiment. This calculation allows us to assign a dominant role to the proximal histidine in the definition of the electronic normal modes and to interpret the transient CD structure observed in a strain of the proximal histidine. This strain builds up in 10 ps and relaxes in 50 ps as the protein evolves towards its deoxy form. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
High‐performance liquid chromatographic enantioseparation of unusual secondary amino acids on a D‐penicillamine‐based chiral ligand exchange column
Authors: Ilisz István , Tourwé Dirk , Armstrong Daniel W. , Péter Antal
Published: March 2006

The application of a chiral ligand‐exchange column (CLEC) for the direct high‐performance liquid chromatographic enantioseparation of unusual secondary amino acids using D‐penicillamine‐Cu(II) complex as chiral selector is reported. The amino acids investigated were pyrrolidine‐2‐carboxylic acid, piperidine‐2‐carboxylic acid, piperazine‐2‐carboxylic acid, morpholine‐3‐carboxylic acid, and thiomorpholine‐3‐carboxylic acid analogs. Chromatographic results are given as the retention, separation, and resolution factors. The chromatographic conditions were varied to achieve optimal separation. The elution sequence of the enantiomers was determined and in most cases the S isomer eluted before R. Chirality 18:539–543, 2006. © 2006 Wiley‐Liss, Inc.
Treatment with taxanes of refractory or life‐threatening Kaposi sarcoma not associated with human immunodeficiency virus infection
Authors: Fardet Laurence , Stoebner Pierre‐Emmanuel , Bachelez Herve , Descamps Vincent , Kerob Delphine , Meunier Laurent , Dandurand Michel , Morel Patrice , Lebbe Celeste
Published: March 2006

BACKGROUND

Kaposi sarcoma (KS) is an angioproliferative disease that may represent a difficult therapeutic challenge in disseminated stages. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties, has been described previously in the treatment of patients with acquired immunodeficiency syndrome (AIDS)‐associated KS but remains unknown in the treatment of patients with refractory or life‐threatening KS without human immunodeficiency (HIV) infection.

METHODS

During the past 6 years, 12 non‐HIV‐infected patients with refractory KS were treated with paclitaxel (175 mg/m2 every 3 wks) or docetaxel (60 mg/m2 every 3 wks).

RESULTS

All patients improved dramatically after chemotherapy. Partial desinfiltration (n = 6) or complete desinfiltration (n = 6) of all papulonodular skin lesions was observed with marked improvement of lymphedema in 6 patients. According to the AIDS Clinical Trials Group criteria, response was partial in 100% of patients. A major response was obtained among patients who had visceral lesions (n = 3 patients), with rapid and complete remission of digestive or respiratory symptoms. The mean delay to response was 2 courses. Treatment was sustained for 3 patients. For the remaining 9 patients who received a median of 7 courses (range, 2‐14 courses), the mean time to recurrence or follow‐up without recurrence was 13 months. Tolerance was good except for 3 episodes of Grade 3 or 4 asymptomatic neutropenia and 1 episode of moderate myositis.

CONCLUSIONS

The results of this study showed that taxanes are beneficial in the treatment of patients with refractory or life‐threatening Kaposi sarcoma. Cancer 2006. © 2006 American Cancer Society.
Soluble Fas—A promising novel urinary marker for the detection of recurrent superficial bladder cancer
Authors: Svatek Robert S. , Herman Michael P. , Lotan Yair , Casella Roberto , Hsieh Jer‐Tsong , Sagalowsky Arthur I. , Shariat Shahrokh F.
Published: March 2006

BACKGROUND

The objective of this study was to test the hypothesis that elevated urinary levels of soluble Fas (sFas) would aid in the surveillance of patients with a past history of nonmuscle‐invasive transitional cell carcinoma (TCC) of the urinary bladder.

METHODS

sFas levels were determined in cell lysates and supernatants from 2 human bladder cancer cell lines (T24 and TCC‐SUP) and in voided urine from 188 consecutive patients who were at risk for TCC recurrence, 31 patients who had noncancerous urologic conditions, and 10 healthy individuals. The authors also obtained barbotage cytology and voided nuclear matrix protein 22 (NMP22) levels. sFas was analyzed continuously and categorically on the basis of its quintile distribution.

RESULTS

sFas was present in cell lysates and conditioned media from both cell lines. sFas levels were found to be higher in the TCC group (n = 122 patients) compared with the control group (P < .001). Higher levels of sFas were associated with positive cytology assay results (P < .001), higher NMP22 levels (P < .001), NMP22 levels > 10 U/mL (P < .001), and tumor stage ≥T1 (P < .001). The areas under the receiver operating characteristics (ROC) curves of sFas and NMP22 for bladder cancer detection were 0.757 (95% confidence interval, 0.694‐0.819) and 0.704 (95% confidence interval, 0.637‐0.772), respectively. In the > 75% sensitivity region of the ROC curves, sFas was consistently more specific than NMP22. In multivariate analyses, sFas, NMP22, and cytology all were found to be associated with the presence of bladder cancer (P values ≤ .009), but only sFas and cytology were associated with tumor stage ≥ T1 (P values ≤ .026).

CONCLUSIONS

sFas was produced and released by bladder TCC cells. Urine sFas was an independent predictor of bladder cancer recurrence and invasiveness in patients who had a past history of nonmuscle invasive bladder TCC, and it outperformed NMP22. Cancer 2006. © 2006 American Cancer Society.
Use of health care services by survivors of childhood and adolescent cancer in Canada
Authors: Shaw Amanda K. , Pogany Lisa , Speechley Kathy N. , Maunsell Elizabeth , Barrera Maru , Mery Leslie S.
Published: March 2006

BACKGROUND

The number of survivors of childhood cancer in Canada is growing. The large majority of survivors experience at least 1 adverse late effect of their cancer therapy, which often becomes more severe and clinically apparent with time. The extent of survivors' use of health services in Canada is unknown, although coordinated, continuous, long‐term follow‐up care has been recommended by numerous investigators.

METHODS

Information on reported consultations with healthcare practitioners in the past year was obtained from 2152 survivors of child and adolescent cancer (mean age at diagnosis, 7.3; range, 0‐19) and 2432 age‐ and sex‐matched population‐based controls through a mailed questionnaire.

RESULTS

Similar proportions of survivors (71%) and controls (73%) reported consulting a general practitioner in the past year. Survivors were more likely than controls to consult with any specialist (68% vs. 46%), including an oncologist (29% vs. 0.3%). Survivors' consultations with oncologists increased with concurrent physical health problems (adjusted odds ratio [ORadj], 1.7, 95% confidence interval [CI], 1.4‐2.1), history of high risk therapy (ORadj, 2.4, 95% CI, 1.9‐2.9), and multiple treatment series (ORadj, 2.2, 95% CI, 1.7‐ 3.0), but decreased with time since diagnosis (ORadj, 0.3, 95% CI, 0.2‐0.4).

CONCLUSION

Although most survivors reported consulting with at least 1 healthcare practitioner in the past year, the large majority did not report consulting an oncologist and thus may not be receiving optimal follow‐up care. Moreover, consultations decreased with time since diagnosis, exactly when risk of late effects increases. This limited preventive care could have major implications on survivors' long‐term health. Cancer 2006. © 2006 American Cancer Society.
Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma
Authors: Kikuchi Shinji , Yamada Daisuke , Fukami Takeshi , Maruyama Tomoko , Ito Akihiko , Asamura Hisao , Matsuno Yoshihiro , Onizuka Masataka , Murakami Yoshinori
Published: March 2006

BACKGROUND

The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC.

METHODS

The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single‐strand conformation polymorphism (SSCP) coupled with bisulfite sequencing.

RESULTS

The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index ≥ 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack‐years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease‐free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients.

CONCLUSIONS

TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis. Cancer 2006. © 2006 American Cancer Society.
Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor‐α and melphalan for limb‐threatening soft tissue sarcoma
Authors: Grunhagen Dirk J. , de Wilt Johannes H. W. , Graveland Wilfried J. , Verhoef Cornelis , van Geel Albertus N. , Eggermont Alexander M. M.
Published: March 2006

BACKGROUND

Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma (STS) of the limb. As it has become apparent that amputation for STS does not improve survival rates, the interest in limb‐preserving approaches has increased. Isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNF) and melphalan is successful in providing local tumor control and enables limb‐preserving surgery in a majority of cases. A mature, large, single‐institution experience with 217 consecutive ILPs for STS of the extremity is reported.

METHODS

At a prospectively maintained database at a tertiary referral center, 217 ILPs were performed from July 1991 to July 2003 in 197 patients with locally advanced STS of the extremity. ILPs were performed at mild hyperthermic conditions with 1–4 mg of TNF and 10–13 mg/L limb‐volume melphalan (M) for leg and arm perfusions, respectively.

RESULTS

The overall response rate was 75%. Limb salvage was achieved in 87% of the perfused limbs. Median survival post‐ILP was 57 months and prognostic factors for survival were Trojani grade of the tumor and ILP for single versus multiple STS. The procedure could be performed safely, with a perioperative mortality of 0.5% in all patients with no age limit (median age, 54 yrs; range, 12–91). Systemic and locoregional toxicity were modest and easily manageable.

CONCLUSION

TNF+M‐based ILP can provide limb salvage in a significant percentage of patients with locally advanced STS and has therefore gained a permanent place in the multimodality treatment of STS. Cancer 2006. © 2006 American Cancer Society.
Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high‐risk sarcomas
Authors: Navid Fariba , Santana Victor M. , Billups Catherine A. , Merchant Thomas E. , Furman Wayne L. , Spunt Sheri L. , Cain Alvida M. , Rao Bhaskar N. , Hale Gregory A. , Pappo Alberto S.
Published: March 2006

BACKGROUND

Intensified chemotherapy may improve the outcome of patients with high‐risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period.

METHODS

In the prospective high‐risk sarcoma (HIRISA) Phase II trial HIRISA1, pediatric patients with high‐risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 with concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support.

RESULTS

Eleven of 24 patients (median age, 14.9 years) had Ewing sarcoma family of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of 11 patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5‐year survival and 5‐year event‐free survival estimates both were 45.8% ± 11.2%.

CONCLUSIONS

The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity. Cancer 2006. © 2006 American Cancer Society.