bluuebunny/crossref_metadata_2025 huggingface dataset:
Subretinal delivery of adeno‐associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice
Authors: Barker Susie E. , Broderick Cathryn A. , Robbie Scott J. , Duran Yanai , Natkunarajah Mythili , Buch Prateek , Balaggan Kamaljit S. , MacLaren Robert E. , Bainbridge James W. B. , Smith Alexander J. , Ali Robin R.
Published: April 2009

Background

Adeno‐associated virus serotype 2 (AAV2) vectors show considerable promise for ocular gene transfer. However, one potential barrier to efficacious long‐term therapy is the development of immune responses against the vector or transgene product.

Methods

We evaluated cellular and humoural responses in mice following both single and repeated subretinal administration of AAV2, and examined their effects on RPE65 and green fluorescent protein transgene expression.

Results

Following subretinal administration of vector, splenocytes and T‐cells from draining lymph nodes showed minimal activation following stimulation by co‐culture with AAV2. Neutralizing antibodies (NAbs) were not detected in the ocular fluids of any mice receiving AAV2 or in the serum of mice receiving a lower dose. NAbs were present in the serum of a proportion of mice receiving a higher dose of the vector. Furthermore, no differences in immunoglobulin titre in serum or ocular fluids against RPE65 protein or AAV2 capsid between treated and control mice were detected. Histological examination showed no evidence of retinal toxicity or leukocyte infiltration compared to uninjected eyes. Repeat administration of low‐dose AAV.hRPE65.hRPE65 to both eyes of RPE65−/− mice resulted in transgene expression and functional rescue, but re‐administration of high‐dose AAV2 resulted in boosted NAb titres and variable transgene expression in the second injected eye.

Conclusions

These data, which were obtained in mice, suggest that, following subretinal injection, immune responses to AAV2 are dose‐dependent. Low‐dose AAV2 is well tolerated in the eye, with minimal immune responses, and transgene expression after repeat administration of vector is achievable. Higher doses lead to the expression of NAbs that reduce the efficacy of repeated vector administration. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis and in vitro evaluation of 18F‐labelled di‐ and tri(ethylene glycol) metomidate esters
Authors: Erlandsson Maria , Hall Håkan , Långström Bengt
Published: April 2009

By replacing the alkyl chain in a metomidate ester with 18F‐labelled di‐ or tri(ethylene glycol) chains, two 18F‐labelled PET tracers, i.e. 2‐(2‐[18F]fluoroethoxy)ethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate (1) and 2‐[2‐(2‐[18F]fluoroethoxy)ethoxy]ethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate (2), were synthesized. Two precursors, 2‐(2‐bromoethoxy)ethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate and 2‐[2‐(2‐chloroethoxy)ethoxy]ethyl 1‐[(1R)‐1‐phenylethyl]‐1H‐imidazole‐5‐carboxylate, were prepared and used in one‐step nucleophilic [18F]fluorination reactions using conventional and microwave heating. Organ distribution, frozen section autoradiography and metabolite analysis were performed. The decay‐corrected radiochemical yields of 1 and 2 were 26±8 and 23±8%, respectively, when they were prepared using conventional heating. By performing microwave heating, the reaction time could be decreased and the yields of analogues 1 and 2 could be increased to 57±12 and 51±18%, respectively. Organ distribution studies in the rat showed considerable uptake in the lungs, adrenals and liver. Both compounds bound with low nonspecific binding (1: approx. 20–30%; 2: 2.9% or lower) to tissue from pig and human normal and pathologic adrenals. Metabolite analyses were performed in rats after 5 and 30 min for tracer 1 (20±6 and 2±1%) and tracer 2 (27±5 and 6±4%). Both compounds are interesting candidates for the detection of different types of adrenal disorders. Copyright © 2009 John Wiley & Sons, Ltd.
Sustainable and balanced development of insular space: the case of Greece
Authors: Christofakis Manolis , Mergos George , Papadaskalopoulos Athanasios
Published: April 2009

Islands, as unique ecosystems, are characterized by a particular sensitivity that affects all the fundamental dimensions of the sustainable development. Thus, highlighting the particularities of the operation of these ecosystems is of considerable importance. This helps to determine the factors and limitations of stability regarding insular ecosystems. All these issues are analysed in this paper. Since they are related to a case study of the Greek insular space, the formulation of a strategic framework for the sustainable and balanced development of the islands is discussed. This strategy is structured by specific priority axes that aim at tackling limitations and expanding the production base, as well as social development. The policies and mechanisms put in place in order to facilitate these priorities are presented too, as well as the necessary supportive and institutional actions. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Instability of the pelvic ring and injury severity can be predictors of death in patients with pelvic ring fractures: a retrospective study
Authors: Tachibana Toshiya , Yokoi Hideyuki , Kirita Manabu , Marukawa Seishiro , Yoshiya Shinichi
Published: April 2009

Background

The correlation between fracture type and mortality in patients with pelvic fracture has been previously investigated. The purpose of this study was to determine whether instability of the pelvic ring as assessed by Tile’s classification is a predictor of death in patients with pelvic fractures.

Materials and methods

The clinical course of consecutive patients with pelvic fractures was retrospectively reviewed. Eighty-seven patients with pelvic ring fractures were included in the study. As potential predictive factors, fracture type according to Tile’s classification, and generally used traumatic parameters (injury severity score, revised trauma score, and probability of survival) were analyzed.

Results

The mortality was significantly higher in patients with unstable fracture patterns (P < 0.05). In non-survivors, index values of traumatic parameters were more severe than those in survivors (P < 0.05).

Conclusion

The present study suggests that patients with unstable pelvic fractures have an increased risk of death associated with exacerbated injury severity.
Depression as a longitudinal outcome and antecedent of preadolescents' peer relationships and peer-relevant cognition
Authors: Zimmer-Gembeck Melanie J. , Hunter Tracey A. , Waters Allison M. , Pronk Rhiarne
Published: April 2009

Using longitudinal data and structural modeling, we investigated bidirectional associations among preadolescents' peer relationships, peer-relevant cognition, and depressive symptoms. Depression was expected to be an outcome and precursor of peer-relevant cognition, and cognition was expected to be an outcome and precursor of being more or less liked by classmates (peer likeability). We also examined whether cognition mediated the association between peer likeability and depression. Participants were 308 students (mean age = 11.0, SD = 0.9) who participated twice during a school year. A third assessment was completed with Grade 5 to 6 students 1 year after the second assessment. The model with bidirectional paths had a good fit to the data, but the most parsimonious model was an “effects” model showing that preadolescents with more depressive symptoms had less positive peer-relevant cognition at later assessments, and that those with more positive peer-relevant cognition were more liked by their peers over time. There were no age differences, some gender differences, and no support for cognition as a moderator of the association between depression and peer likeability.
Earth's global Ag, Al, Cr, Cu, Fe, Ni, Pb, and Zn cycles
Authors: Rauch Jason N. , Pacyna Jozef M.
Published: April 2009

The stocks and flows of the global silver, aluminum, chromium, copper, iron, nickel, lead, and zinc cycles quantify over 98% of the total mass of metal mobilized by human activity at the turn of the 21st century. Iron and aluminum, representing >95% by mass of all metals mined, are for the first time assessed for global anthropogenic emissions to air, water, and land. Anthropogenic activity has significantly perturbed Earth's natural biogeochemical cycles, attested by the “grand nutrient” cycles of carbon, nitrogen, phosphorous, and sulfur and further revealed here by the “anthrobiogeochemical” cycles of metals. We demonstrate that humans today mobilize about half the metal mass of these global elemental metal cycles.
Graph analysis of cortical networks reveals complex anatomical communication substrate
Authors: Zamora-López Gorka , Zhou Changsong , Kurths Jürgen
Published: April 2009

Sensory information entering the nervous system follows independent paths of processing such that specific features are individually detected. However, sensory perception, awareness, and cognition emerge from the combination of information. Here we have analyzed the corticocortical network of the cat, looking for the anatomical substrate which permits the simultaneous segregation and integration of information in the brain. We find that cortical communications are mainly governed by three topological factors of the underlying network: (i) a large density of connections, (ii) segregation of cortical areas into clusters, and (iii) the presence of highly connected hubs aiding the multisensory processing and integration. Statistical analysis of the shortest paths reveals that, while information is highly accessible to all cortical areas, the complexity of cortical information processing may arise from the rich and intricate alternative paths in which areas can influence each other.
Field induced domain wall collisions in thin magnetic nanowires
Authors: Kunz Andrew
Published: April 2009

In a two-dimensional magnetic nanowire, it is possible to engineer collisions between two domain walls put into motion by an externally applied field. We show that the topological defects that define the domain wall can be controlled to allow for both domain wall annihilation and preservation during the collisions as long as the wire remains thin. The preservation process can be used to release pinned domain walls from notches with small applied fields.
Achievements and challenges in bilingual and multilingual education in the Basque Country
Authors: Cenoz Jasone
Published: April 2009

This paper focuses on the use of Basque as the language of instruction. In the first part of the article the situation of Basque in the Basque Country is briefly described and the different possibilities regarding the language(s) of instruction are explained: model A with Spanish as the language of instruction and Basque as a subject; model B with both Basque and Spanish as languages of instruction and model D with Basque as the language of instruction and Spanish as a subject. Then, the results of research studies comparing these three models regarding achievement in Basque, Spanish and other areas of the curriculum are analysed. Finally the article considers the new challenges the Basque educational system is facing. One of these challenges is the need to go from bilingual education to multilingual education by teaching in a more effective way languages of wider communication. Another recent challenge is multiculturalism as a response to the increasing immigrant population which is a new phenomenon in the Basque educational system. The need for a more holistic approach towards multilingualism both in teaching and research is proposed so as to face these new challenges.
Identifying key sociophilological usage in plays and trial proceedings (1640–1760)
Authors: Archer Dawn , Culpeper Jonathan
Published: April 2009

In this paper, we argue that there is another approach to the study of historical pragmatics beyond those explicitly mentioned in Jacobs and Jucker (1995). We label this approach “sociophilology”. Moreover, we demonstrate how this approach can be effectively pursued by combining two corpus linguistics techniques: corpus annotation and “keyness” analysis. Specifically, we draw from the Sociopragmatic Corpus (1640–1760), an annotated subsection of comedy plays and drama proceedings taken from the Corpus of Dialogues 1560–1760, as a means of identifying the statistically-based style markers, or key items, associated with a number of social role dyads (including examiner to examinee and master/mistress to servant). We will show how such an approach might be used to uncover differential distributions of personal pronouns, interjections, imperative verbs, politeness formulae, etc., and how, by combining qualitative analysis with quantitative analysis, one can scrutinise such material for pragmatic import.
Heterogeneity of Stimulant Dependence: A National Drug Abuse Treatment Clinical Trials Network Study
Authors: Wu Li‐Tzy , Blazer Dan G. , Patkar Ashwin A. , Stitzer Maxine L. , Wakim Paul G. , Brooner Robert K.
Published: April 2009

We investigated the presence of DSM‐IV subtyping for dependence on cocaine and amphetamines (with versus without physical dependence) among outpatient stimulant users enrolled in a multisite study of the Clinical Trials Network (CTN). Three mutually exclusive groups were identified: primary cocaine users (n = 287), primary amphetamine users (n = 99), and dual users (cocaine and amphetamines; n = 29). Distinct subtypes were examined with latent class and logistic regression procedures. Cocaine users were distinct from amphetamine users in age and race/ethnicity. There were four distinct classes of primary cocaine users: non‐dependence (15%), compulsive use (14%), tolerance and compulsive use (15%), and physiological dependence (tolerance, withdrawal, and compulsive use; 56%). Three distinct classes of primary amphetamine users were identified: non‐dependence (11%), intermediate physiological dependence (31%), and physiological dependence (58%). Regardless of stimulants used, most female users were in the most severe or the physiological dependence group. These results lend support for subtyping dependence in the emerging DSM‐V.
Revised scaling equation for the prediction of tritium retention in beryllium co-deposited layers
Authors: De Temmerman G. , Doerner R.P.
Published: April 2009

The prediction of tritium retention in ITER relies on the extrapolation from present data. An empirical equation was proposed in (De Temmerman G. et al
2008 Nucl. Fusion
48 075008) to account for the influence of the beryllium deposition rate, the substrate temperature and the average energy of the deuterium neutrals on the deuterium retention. However, the beryllium deposition rate observed in PISCES-B is much lower than that expected in the ITER divertor. On the other hand, the flux ratios of deuterium and beryllium are comparable in magnitude. Therefore, a revised scaling equation is proposed here to take into account the flux ratio of deuterium to beryllium arriving at the co-depositing surface and to match the validity range of the scaling equation with the ITER parameters.
Schooling pattern of eastern Bering Sea walleye pollock and its effect on fishing behaviour
Authors: Shen Haixue , Dorn Martin W. , Wespestad Vidar , Quinn Terrance J.
Published: April 2009

Shen, H., Dorn, M. W., Wespestad, V., and Quinn, T. J. 2009. Schooling pattern of eastern Bering Sea walleye pollock and its effect on fishing behaviour. – ICES Journal of Marine Science, 66: 1284–1288 Walleye pollock (Theragra chalcogramma) form persistent midwater and near-bottom schools in the daytime during the winter spawning season in the eastern Bering Sea (EBS). Two spawning areas in the EBS, north of Unimak Island and near the Pribilof Islands, are the main fishing grounds. To study the schooling pattern of pollock and its effect on fishing behaviour on these two fishing grounds, a principal component analysis with instrumental variables was carried out using acoustic and observer data from 2003 and 2005. Significant differences between the school descriptors distinguished the schooling patterns among areas and years. The harvester, that is to say, the fishing vessel and its crew taken together, searched for fish aggregations, which were caught in a different manner when the schooling pattern changed. School density had a greater effect than school size on fishing behaviour. Aggregations were less dense in 2003 than in 2005, and the harvester tended to fish with longer tows, at higher speeds, when it encountered less dense aggregations.
Mouse models of human AML accurately predict chemotherapy response
Authors: Zuber Johannes , Radtke Ina , Pardee Timothy S. , Zhao Zhen , Rappaport Amy R. , Luo Weijun , McCurrach Mila E. , Yang Miao-Miao , Dolan M. Eileen , Kogan Scott C. , Downing James R. , Lowe Scott W.
Published: April 2009

The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients.
Purification of Recombinant Drosophila NAP1
Authors: Peterson Craig L.
Published: April 2009

INTRODUCTION

The goal of chromatin assembly procedures is to prepare extended nucleosomal arrays from cloned DNA templates and purified core and linker histones. The assembled chromatin should be highly defined in its protein content and resemble bulk chromatin isolated from living cell nuclei in terms of periodicity and nucleosome positioning. This protocol describes the preparation of the NAP1 chaperone protein for use in chromatin assembly reactions. In this method, Sf9 cells are infected with an HIS6-DNA-1-expressing baculovirus. The NAP1 is then purified by nickel affinity chromatography, followed by anion-exchange chromatography.
Whole-Mount Preparation of Helobdella (Leech) Embryos for Microscopy
Authors: Weisblat David A. , Kuo Dian-Han
Published: April 2009

INTRODUCTION

Due to the high yolk content and relatively large size of the Helobdella (leech) embryo, it is preferable to examine the embryos in a cleared whole-mount preparation after they have been stained. Three whole-mount procedures suitable for leech embryos are described here. The glycerol whole mount is quick and convenient because it does not require dehydration. However, prolonged incubation in buffered glycerol could cause the yolk to turn dark purple. Thus, it is not suitable for yolk-containing specimens that are intended for light microscopy. For fluorescence microscopy, anti-fading reagent can be added to the buffered glycerol. This article includes a recipe that works quite well for leech embryos. Also included are two alternative methods that require embryo dehydration, but have the advantage of clearing yolk-containing tissue. One method relies on the use of benzyl benzoate:benzyl alcohol (BBBA), a solution that provides the best clearing of yolk-containing tissue in the leech embryo. It is suitable for both fluorescence and light microscopy. Another alternative is the Epon whole-mount preparation. Epon is not quite as effective in clearing the yolk, but the viscosity of Epon facilitates orienting the specimens for imaging. As with BBBA, Epon is suitable for both light and fluorescence microscopy.
Serendipitous evidence of T lymphocyte activation in close female relatives of patients with systemic lupus erythematosus
Authors: Green M R J , Kennell A S M , Larche M J , Seifert M H , Isenberg D A , Salaman M R
Published: April 2009

A well-recognized characteristic of the autoimmune disease, systemic lupus erythematosus (SLE), is the high level of activated T cells present in the blood. Because of the increased size and granularity of activated T cells, in flow cytometry one might expect to find increased numbers of cells falling outside a standard light-scatter lymphocyte gate, and indeed we now report that the percentage of T lymphocytes in the gate (% TiG) was below the normal range in 23 of 58 (40%) female patients because of increased scatter values. However, the surprising additional observation was made that 18 of 30 (60%) female first-degree relatives of the patients also fell below the normal % TiG range, suggesting the presence of T cell activation in these relatives. This view is strengthened by the strong inverse correlation between plasma total immunoglobulin G(IgG), which was raised in some relatives, and % TiG, as T cell activation is a requirement for IgG production. Conversely, there was no correlation with IgM, which has no comparable link with T cell activation. While a definitive interpretation must await the demonstration of activation antigen expression in relatives, these findings suggest the existence of a T cell activation trait, not harmful in itself, which, however, contributes to the development of disease in patients with SLE.
Improving client‐centred care and services: the role of front/back‐office configurations
Authors: Broekhuis Manda , De Blok Carolien , Meijboom Bert
Published: April 2009

Title.  Improving client‐centred care and services: the role of front/back‐officeconfigurations.

Aim.  This paper is a report of a study conducted to explore the application of designing front‐ and back‐office work resulting in efficient client‐centred care in healthcare organizations that supply home care, welfare and domestic services.

Background.  Front/back‐office configurations reflect a neglected domain of design decisions in the development of more client‐centred processes and structures without incurring major cost increases.

Method.  Based on a literature search, a framework of four front/back‐office configurations was constructed. To illustrate the usefulness of this framework, a single, longitudinal case study was performed in a large organization, which provides home care, welfare and domestic services for a sustained period (2005–2006).

Findings.  The case study illustrates how front/back‐office design decisions are related to the complexity of the clients’ demands and the strategic objectives of an organization. The constructed framework guides the practical development of front/back‐office designs, and shows how each design contributes differently to such performance objectives as quality, speed and efficiency.

Conclusions.  The front/back‐office configurations presented comprise an important first step in elaborating client‐centred care and service provision to the operational level. It helps healthcare organizations to become more responsive and to provide efficient client‐centred care and services when approaching demand in a well‐tuned manner. In addition to its applicability in home care, we believe that a deliberate front/back‐office configuration also has potential in other fields of health care.
Risk Factors Associated with Fibular Fracture After Tibial Plateau Leveling Osteotomy
Authors: TUTTLE TRENT A. , MANLEY PAUL A.
Published: April 2009

Objective— To determine the incidence of, and risk factors for, fibular fracture after tibial plateau leveling osteotomy (TPLO) in dogs.

Study Design— Case series.

Sample Population— TPLO (n=168) on 142 dogs.

Methods— Medical records (January 2006–September 2007) and radiographs of all dogs that had TPLO were reviewed. Data retrieved were breed, sex, age, weight, type of plate, use of a jig, time to recheck, preoperative tibial plateau angle (TPA), immediate postoperative TPA, and presence or absence of fibular fracture.

Results— Fibular fractures occurred in 5.4% TPLOs. Body weight, change in TPA, and preoperative TPA were significantly higher in dogs with fibular fracture. TPLO without use of a jig was significantly associated with fibular fracture. Age, postoperative TPA, and plate type were not significantly associated with fibular fracture.

Conclusions— Fibular fracture is uncommon after TPLO. Risk factors are increased body weight, greater preoperative TPA, greater change in TPA, and TPLO performed without a jig. All fractures occurred during convalescence.

Clinical Relevance— Owners should be warned of potential complications and risk factors associated for fibular fracture after TPLO.
A Hemodynamically Responsive Antitachycardia System: Theoretical Bases for Design
Authors: COHEN TODD J. , VELTRI ENRICO P. , MOWER MORTON M.
Published: April 2009

Current antitachycardia systems such as the automatic implantable cardioverter/defibrillator (AICD), detect tachyarrhythmias primarily by sensing rate and thereby perform inadequately in differentiating hemodynamically stable from unstable arrhythmias. As a result, these devices may discharge during stable tachycardias (such as sinus tachycardia), causing discomfort to the patient and depleting the device's limited energy supply. If a parameter which could reflect the particular hemodynamic state of a tachycardia were incorporated into the sensing algorithm of these systems, function may be more hemodynamically precise and discharge specificity may be improved.
Effect of Basic Drive Train Cycle Length on Induction of Ventricular Tachycardia by a Single Extrastimulus
Authors: MORADY FRED , KOU WILLIAM H. , KADISH ALAN H. , SCHMALTZ STEPHEN , SUMMITT JONI , ROSENHECK SHIMON
Published: April 2009

This study determined the effects of a wide range of basic drive cycle lengths on the induction of ventricular tachycardia (VT) by a single extrastimulus (S2). Seventy‐one patients with coronary artery disease and inducible sustained monomorphic VT underwent 121 electrophysiology tests either in the control state or during treatment with an antiarrhythmic drug. Ventricular basic drive trains were eight beats in duration and the intertrain interval was three seconds. Programmed ventricular stimulation was performed with S2 using the longest possible basic drive cycle length rounded off to the nearest multiple of 100 msec, then using basic drive train cycle lengths that decreased in 100 msec steps to 400 msec, and finally using a basic drive cycle length of 350 msec. At each drive cycle length, an interval of > 50 msec beyond the effective refractory period (ERP) was scanned with S2. Monomorphic VT was induced by S2 in 52/121 studies (43%). The drive cycle length had a significant linear effect on the log odds of inducing VT (P < 0.0001). The highest yield of VT occurred with a drive cycle length of 350 msec (42/121, 34%), and with each increment in drive cycle length, the expected odds of inducing VT decreased by a factor of 1.7. In 88% of cases in which VT was induced at a particular drive cycle length but not at longer drive cycle lengths, the coupling intervals that induced VT exceeded the ERP measured at one or more of the longer basic drive cycle lengths. In conclusion, there is an inverse relationship between the basic drive cycle length and the yield of monomorphic VT induced by S2. The use of shorter basic drive cycle lengths often facilitates the induction of VT by some effect other than critical shortening of the S2 coupling interval.
A Mathematical Model of the Cardiac Chronotropic Response to Exercise
Authors: WILKOFF BRUCE L. , COREY JOSEPH , BLACKBURN GORDON
Published: April 2009

A mathematical model was developed from data collected from 410 normal subjects in order to describe the normal cardiac Chronotropic response to exercise. Subjects were examined by treadmill testing on either the Bruce protocol (189 patients) or the Chronotropic Assessment Exercise Protocol (CAEP) (221 patients), The CAEP, designed specifically for chronotropic assessment, is structured to collect heart rate data at submaximal as well as peak exercise intensities. Analysis of these subjects, without evidence of medical illness or cardiac medications, found the heart rate response to be a function of exercise intensity, age, resting heart rate, and maximal functional capacity. Heart rate reserve (HRR) was defined as the difference betii'een maximal predicted heart rate (MPHR) and resting heart (HRrest). Metabolic reserve was defined as the difference between the maximally achieved workload (METSpeak) and the workload at rest (METSrest). The Bruce and CAEP data provided a statistically linear and identical response of the form y = mx + b. The Bruce equation was %HRR = 0.95 ×%MR + 3.4 and the CAEP equation is %HRR = 0.94 ×%MR + 4.55. The following formula describes the normal predicted heart rate for an individual at some submaximal stage of exercise: HRstage= [(220 ‐ age ‐HRrest) × (METSstage ‐ 1)/(METSpeak ‐ 1)] + HRrest. We conclude that the cardiac chronotropic response can be modeled as a simple linear mathematical function of exercise intensity, age, resting heart rate, and maximal functional capacity, and is independent of type of treadmill exercise protocol in normal subjects.
Catheter Ablation of Ventricular Endocardium Using Radiofrequency Energy: Determinants of Lesion Volume and Shape
Authors: GROGAN E. WAYNE , NELLIS STEPHEN H. , SUBRAMANIAN RAMIAH
Published: April 2009

Radiofrequency energy was delivered at varying powers and durations to excised portions of canine left ventricle that were mounted in a tank of saline at room temperature. A radiofrequenciy generator delivered alternating current in a sine wave pattern at a frequency of 500 kHz, at variable voltage. In each of five excised ventricles, 49 lesions were created, at delivered RMS voltages from 18 to 40 V and durations of ablation from 5 to 180 seconds. Lesion diameter and depth were measured grossly, and lesion volume and shape (ratio of radius/depth) were calculated. Lesion diameter, depth, and volume increased with increasing power and duration of energy delivery, and the relation of delivered energy (joules) to calculated lesion volume (mm3) was linear (r = 0.88, P < 0.001). Shallower lesions were produced by shorter duration of energy delivery at all power levels, and similar volume but deeper, more symmetric lesions by lower power and longer duration of energy delivery. Radiofrequency energy in vitro thus produces reproducible lesions whose volume is proportional to delivered energy, and whose shape can be altered by delivering similar total energies, but varying the power and duration of energy delivery
Structural features and dynamics of a cold‐adapted alkaline phosphatase studied by EPR spectroscopy
Authors: Heidarsson Pétur O. , Sigurdsson Snorri Th , Ásgeirsson Bjarni
Published: April 2009

EPR spectroscopy, performed after site‐directed spin‐labeling, was used to study structural dynamics in a cold‐adapted alkaline phosphatase (EC 3.1.1.1). Differences in the structural environment of six spin‐labeled side chains allowed them to be classified (with reference to previously obtained mobility maps) as belonging to loop positions (either relatively surface exposed or in structural contact) or helix positions (surface exposed, in contact, or buried). The mobility map constructed in the present study provides structural information that is in broad agreement with the location in the crystal structure. All but one of the chosen serine‐to‐cysteine mutations reduced activity considerably and this coincided with improved thermal stability. The effect of spin‐labeling on enzyme function ranged from nonperturbing to an almost complete loss of activity. In the latter case, treatment with a thiol reagent reactivated the enzyme, indicating relief of steric hindrance to the catalytic process. Two mutations of an active‐site residue W274 (K328 in Escherichia coli alkaline phosphatase), known to reduce activity and increase stability of Vibrio alkaline phosphatase, gave a coincidental reduction in mobility of a nearby spin‐label located at C67, as determined by EPR spectroscopy. This suggests that movement of the helix carrying C67 and the closely positioned nucleophilic S65 is interconnected with catalytic events.
Evaluation of Combined Direct‐Push Methods Used for Aquifer Model Generation
Authors: Köber Ralf , Hornbruch Götz , Leven Carsten , Tischer Lars , Großmann Jochen , Dietrich Peter , Weiß Holger , Dahmke Andreas
Published: April 2009

Most established methods to characterize aquifer structure and hydraulic conductivities of hydrostratigraphical units are not capable of delivering sufficient information in the spatial resolution that is desired for sophisticated numerical contaminant transport modeling and adapted remediation design. With hydraulic investigation methods based on the direct‐push (DP) technology such as DP slug tests, DP injection logging, and the hydraulic profiling tool, it is possible to rapidly delineate hydrogeological structures and estimate their hydraulic conductivity in shallow unconsolidated aquifers without the need for wells. A combined application of these tools was used for the investigation of a contaminated German refinery site and for the setup of hydraulic aquifer models. The quality of DP investigation and the models was evaluated by comparisons of tracer transport simulations using these models and measured breakthroughs of two natural gradient tracer tests. Model scenarios considering the information of all tools together showed good reproduction of the measured breakthroughs, indicating the suitability of the approach and a minor impact of potential technical limitations. Using the DP slug tests alone yielded significantly higher deviations for the determined hydraulic conductivities compared to considering two or three of the tools. Realistic aquifer models developed on basis of such combined DP investigation approaches can help optimize remediation concepts or identify flow regimes for aquifers with a complex structure.
Zinc Avoidance by Fathead Minnows (Pimephales promelas): Computerized Tracking and Greater Ecological Relevance
Authors: Korver R. M. , Sprague J. B.
Published: April 2009

Male fathead minnows (Pimephales promelas) avoided 0.284 mg∙L−1 of zinc when given a choice of clean and dosed sides of a featureless openfield tank, as frequently used in avoidance/preference experiments. More than six times as much zinc (1.83 mg∙L−1) was required to cause avoidance when males were allowed to establish a territory under a shelter on the side of the experimental chamber which was later dosed. Activity increased during zinc dosing when a shelter was present but did not change in no-shelter tests. Control period activity was positively related to strength of avoidance response. By incorporating relevant motivational factors, behaviour observed in avoidance experiments should be more predictive to nature. A new computerized tracking system automatically recorded movements of the fish, calculated various measures of locomotor response and filed results in preparation for statistical analysis.
Radioisotopic study of11C-labelling methanol decomposition on iron oxide modified mesoporous MCM-41 silica
Authors: Sarkadi-Pribóczki Eva , Tsoncheva Tanya , Ivanova Ljubomira
Published: April 2009

Novel11C-radiolabelling method was applied for the investigation of methanol conversion on iron oxide modified mesoporous MCM-41. Changes in the selectivity were observed varying the state of the loaded iron species or the degree of the surface coverage with11C-radiolabelling methanol. Combining the Moessbauer spectroscopy, X-ray diffraction (XRD), N2-physisorption, and temperature-programmed reduction- thermogravimetric (TPR-TG) techniques with the high sensitive11C-radioisotopic catalytic analysis, the contribution of the different reaction pathways of methanol conversion was discussed.
Magnetic separable PSA@Fe3O4/Ag composites — Fabrication and catalytic properties
Authors: Jiang Cuifeng , Chen Mingwei , Xuan Shouhu , Jiang Wanquan , Gong Xinglong , Zhang Zhong
Published: April 2009

A novel PSA@Fe3O4/Ag composite, with high efficiency in the degradation of Rhodamine B, was synthesized through a simple wet-chemistry method. The results showed that the rate of the catalytic reaction was significantly concentration-dependent. Furthermore, there was no significant loss in the catalytic activity of the recycled catalysts, even after being recycled nine times (average 83%), from which one can deduce that almost all the nanosilver were regathered due to the super-paramagnetic Fe3O4 nanoparticles.
DYNAMICAL GAPS AND QUANTUM HALL EFFECT IN GRAPHENE
Authors: GORBAR E. V. , GUSYNIN V. P. , MIRANSKY V. A.
Published: April 2009

We analyze the gap equation for Dirac quasiparticles in graphene in a magnetic field using a low-energy effective model with a contact interaction. It is found that the order parameters connected with the quantum Hall (QH) ferromagnetism and the magnetic catalysis scenarios necessarily coexist. The ground-state solutions of the gap equation describe all the recently discovered novel QH plateaus in graphene in strong magnetic fields.
Influence of Task Predictability on the Activity of Neurons in the Rostral Superior Colliculus During Double-Step Saccades
Authors: Reyes-Puerta Vicente , Philipp Roland , Lindner Werner , Lünenburger Lars , Hoffmann Klaus-Peter
Published: April 2009

Target probability has been shown to modulate motor preparatory activity of neurons in the caudal superior colliculus (SC) of the primate. Here we tested whether top-down processes, such as task predictability, influence the activity of neurons also at the rostral pole of the SC (rSC), classically related to fixation. To investigate this, double-step saccade tasks were embedded in two different paradigms, one containing unpredictable and another containing predictable tasks. During predictable tasks the animals could develop some expectation about the forthcoming second target jump, i.e., anticipate when and where to make the second saccade. Neuronal responses were recorded during both paradigms and compared, revealing the influence of task predictability on the activity of rSC neurons during specific periods of fixation. In particular, neuronal activity stayed significantly lower during the fixation period between two successive saccades in predictable than in unpredictable tasks. In addition there was a learning effect within a session during predictable conditions, i.e., the intersaccadic activity was higher in the early than in the late trials. Further, reaction times for the second saccade were shorter in predictable than in unpredictable tasks. However, we demonstrated that this difference in reaction times cannot be solely accounted for by the reported difference in neural activity, which was mainly influenced by the predictability of the tasks. With these results we show that top-down processes such as predictability are imposed on the activity of neurons in the rostral pole of the primate SC.
Effect of Premelting on Conductivity of DNA-Lipid Films
Authors: Kasumov A. Yu. , Nakamae S. , Cazayous M. , Kawasaki T. , Okahata Y.
Published: April 2009

We have measured temperature-dependent (between 20 and80∘C) electrical conductivity and molecular structure (Raman spectroscopy) of DNA-lipid cast film. Our findings show that the conductivity is strongly influenced by premelting effects in the molecular structure starting near physiological temperatures (∼40∘C), prior to the global DNA denaturation.
The Receptor Interacting Protein 1 Inhibits p53 Induction through NF-κB Activation and Confers a Worse Prognosis in Glioblastoma
Authors: Park Seongmi , Hatanpaa Kimmo J. , Xie Yang , Mickey Bruce E. , Madden Christopher J. , Raisanen Jack M. , Ramnarain Deepti B. , Xiao Guanghua , Saha Debabrata , Boothman David A. , Zhao Dawen , Bachoo Robert M. , Pieper Russell O. , Habib Amyn A.
Published: April 2009

Nuclear factor-κB (NF-κB) activation may play an important role in the pathogenesis of cancer and also in resistance to treatment. Inactivation of the p53 tumor suppressor is a key component of the multistep evolution of most cancers. Links between the NF-κB and p53 pathways are under intense investigation. In this study, we show that the receptor interacting protein 1 (RIP1), a central component of the NF-κB signaling network, negatively regulates p53 tumor suppressor signaling. Loss of RIP1 from cells results in augmented induction of p53 in response to DNA damage, whereas increased RIP1 level leads to a complete shutdown of DNA damage–induced p53 induction by enhancing levels of cellular mdm2. The key signal generated by RIP1 to up-regulate mdm2 and inhibit p53 is activation of NF-κB. The clinical implication of this finding is shown in glioblastoma, the most common primary malignant brain tumor in adults. We show that RIP1 is commonly overexpressed in glioblastoma, but not in grades II and III glioma, and increased expression of RIP1 confers a worse prognosis in glioblastoma. Importantly, RIP1 levels correlate strongly with mdm2 levels in glioblastoma. Our results show a key interaction between the NF-κB and p53 pathways that may have implications for the targeted treatment of glioblastoma. [Cancer Res 2009;69(7):2809–16]
Chemoprevention of Human Actinic Keratoses by Topical dl-α-tocopherol
Authors: Foote Janet A. , Ranger-Moore James R. , Einspahr Janine G. , Saboda Kathylynn , Kenyon Jaime , Warneke James , Miller Richard C. , Goldman Rayna , Xu Min-Jian , Roe Denise J. , Alberts David S.
Published: April 2009

Prior research shows that topical application of free, nonfatty acid–conjugated vitamin E (dl-α-tocopherol) prevents skin cancer in mice, as well as immunosuppression induced by UVB radiation. This study investigated the chemopreventive potential of dl-α-tocopherol in humans through monitoring surrogate end point biomarkers in sun-damaged skin. Contralateral arms of healthy human volunteers with actinic keratoses (AK) were randomly assigned to receive either 12.5% dl-α-tocopherol or placebo in a crème base for 6 months. Changes in number of AKs, levels of p53 protein expression, proliferating cell nuclear antigen, and polyamines were assessed along with skin and systemic vitamin E levels. Following treatment, plasma concentration levels of dl-α-tocopherol were unchanged, but skin levels were highly elevated (P < 0.001). Levels of p53 and proliferating cell nuclear antigen did not change significantly, whereas number of AKs declined insignificantly in both placebo and treatment arms. Regression models showed significant decreases in putrescine, spermidine, spermine, and total polyamine concentrations following treatment. Topically applied dl-α-tocopherol was substantially absorbed in skin, but the 6-month application did not significantly reduce numbers of preexisting AKs on moderately to severely sun-damaged forearms. Increases in polyamine synthesis are expected during tumor initiation and promotion; conversely, the significant reductions in polyamine levels resulting from the topical dl-α-tocopherol application are consistent with reductions in tumorigenesis potential. Topical tocopherol did not normalize established sun-induced lesions, but dl-α-tocopherol–induced reductions in polyamine metabolism are consistent with the inhibition of skin squamous cell carcinogenesis as seen in previous human trials and animal models.
The Dominance Entry of the Principles of Ghārār in Electronic Contracts
Authors: Razali Siti Salwani
Published: April 2009

Contracts feature in all areas of our daily lives. For example, without much thought, we become party to a variety of contracts when we travel by bus or rail, purchase goods, accept services, and carry out our duties in the workplace. Contracts are so prevalent that ordinary men or women in the street do not realize the legal complexities of the transactions into which they enter. The use of Internet as a medium of communication has widened the scope for contract formation. Sales and purchase activities are conducted online using contracts either drawn up through the Internet itself or outside cyberspace. Several areas of uncertainty will have a significant impact on electronic contracting under Islamic Shari'ah law. This is a fundamental issue, especially with regard to online contracts for which the contracting parties are not physically present. In fact, if certain fundamental issues regarding online contracts are not resolved, then the dominance entry of the principles of ghārār (uncertainty) will apply, making such contracts unfeasible under Islamic Shari'ah law. Therefore, this paper aims to review what is actually meant by ghārār and how it affects the enforceability of electronic contracts under Shari'ah law. It also suggests how ghārār can be reduced or even eliminated to achieve an acceptable degree of certainty, thus enabling the practice of online contracts, particularly according to the Shari'ah.
‘A Prey on Normal People’: C. Killick Millard and the Euthanasia Movement in Great Britain, 1930–55
Authors: Dowbiggin Ian
Published: April 2009

Few issues in medicine and society today are more controversial than euthanasia, the term derived from the Greek word for ‘easy death’ and often called ‘mercy-killing’. Current debates raise questions about the past and what euthanasia has meant to earlier generations. The most infamous example of a state euthanasia programme occurred between 1939 and 1945 in nazi Germany when thousands of handicapped men, women and children were murdered. But little is known about the history of Anglo-American euthanasia. This article, based on an examination of documents from a variety of archival collections in England and the USA, explores the early history of the unsuccessful movement to legalize euthanasia in Great Britain, as embodied in the Voluntary Euthanasia Legislation Society (VELS). By focusing on the career of C. Killick Millard (1870–1952), the founder of the VELS, this article argues that although the VELS tried to convince the public that it sought the legalization of only mercy-killing with consent, there was a tendency within the VELS to obscure the distinctions between voluntary and involuntary euthanasia. There is even some evidence of VELS sympathy for nazi euthanasia. At the same time, VELS members also tended to be involved in the eugenics, birth control and public health movements or belong to liberal religious groups like the Unitarians, or they were physicians radicalized by the experience of watching patients die in protracted agony. It is this complex constellation of motives — some murky and some indisputably humane — that warrants attention nowadays, at a time when courts and legislatures are being asked to rule on such literally life and death issues.
Britain's Image Campaign against the Zionists
Authors: Kochavi Arieh J.
Published: April 2009

Britain's struggle against the Zionists after the second world war involved the mounting of a propaganda campaign, the aim of which was to sway attention away from the plight of the survivors of the Holocaust and to present these now displaced persons as participants in a nationalistic struggle. This included portraying Zionist activists as shrewd, unscrupulous people who were willing to adopt any means, the exploitation of suffering DPs included, to achieve their nationalistic goals. For their part, the Zionists appealed to world opinion by emphasizing both the distress of the survivors of the Holocaust in the DP camps in Germany and Austria, and the need to accept Palestine as the only solution to their plight.