bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a high‐dose nitrate strategy on cardiac stress in acute heart failure: a pilot study
Authors: Breidthardt T. , Noveanu M. , Potocki M. , Reichlin T. , Egli P. , Hartwiger S. , Socrates T. , Gayat E. , Christ M. , Mebazaa A. , Mueller C. 
Published: June 2009

Abstract.  Breidthardt T, Noveanu M, Potocki M, Reichlin T, Egli P, Hartwiger S, Socrates T, Gayat E, Christ M, Mebazaa A, Mueller C (University Hospital, Basel, Switzerland, University Paris, Paris, France, and Klinikum Nürnberg, Nürnberg, Germany). Impact of a high‐dose nitrate strategy on cardiac stress in acute heart failure: a pilot study. J Intern Med 2010; 267: 322–330.Background.  Intravenous nitrate therapy has been shown to improve short‐term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high‐dose nitrate strategy in the Emergency Department and the general ward remains unknown.Methods.  A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high‐dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B‐type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy.Results.  The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2–120.6) vs. 20 mg (10–30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high‐dose nitrate group (P < 0.0001). The larger decrease in BNP in the high‐dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 ± 4.9% in the high‐dose nitrate strategy group compared to 15 ± 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high‐dose nitrate group [high‐dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In‐hospital and 90‐day outcome was similar amongst the two groups.Conclusions.  A noninvasive high‐dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.
Halton sampling for autofocus
Authors: PENGO T. , MUÑOZ‐BARRUTIA A. , ORTIZ‐DE‐SOLÓRZANO C. 
Published: June 2009

SummaryReliable autofocusing is a critical part of any automated microscopy system: by precisely positioning the sample in the focal plane, the acquired images are sharp and can be accurately segmented and quantified. The three main components of an autofocus algorithm are a contrast function, an optimization algorithm and a sampling strategy. The latter has not been given much attention in the literature. It is however a very important part of the autofocusing algorithm, especially in high content and high throughput image‐based screening. It deals with the problem of sampling the focus surface as sparsely as possible to reduce bleaching and computation time while with sufficient detail as to permit a faithful interpolation. We propose a new strategy that has higher performance compared to the classical square grid or the hexagonal lattice, which is based on the concept of low discrepancy point sets and in particular on the Halton point set. We tested the new algorithm on nine different focus surfaces, each under 24 different combinations of Signal‐to‐Noise ratio (SNR) and sampling rate, obtaining that in 88% of the tested conditions, Halton sampling outperforms its counterparts.
TEM foil preparation of sub‐micrometre sized individual grains by focused ion beam technique
Authors: HOLZAPFEL C. , SOLDERA F. , VOLLMER C. , HOPPE P. , MÜCKLICH F. 
Published: June 2009

SummaryAnalysis of presolar silicate grains provides new knowledge on interstellar and circumstellar environments and can be used to test models of the Galactic chemical evolution. However, structural information of these grains is rare because sample preparation for transmission electron microscopy is very difficult due to the small dimensions of these grains (<0.5 μm). With the use of the focused ion beam technique thin foils from these grains for transmission electron microscopy analysis can be prepared. Nevertheless, reaching the required precision of some tens of nanometres for the preparation of the transmission electron microscopy foil in the place of interest is not trivial. Furthermore, in the current samples, the grain of interest can only be identified by its different isotopic composition; i.e. there is no contrast difference in scanning electron microscopy or transmission electron microscopy images which allow the identification of the grain. Therefore, the grain has to be marked in some way before preparing the transmission electron microscopy foil. In the present paper, a method for transmission electron microscopy foil preparation of grains about 200 to 400 nm in diameter is presented. The method utilizes marking of the grain by Pt deposition and milling of holes to aid in the exact orientation of the transmission electron microscopy foil with respect to the grain. The proposed method will be explained in detail by using an example grain.
EBSD for analysing the twinning microstructure in fine‐grained TWIP steels and its influence on work hardening
Authors: BARBIER D. , GEY N. , BOZZOLO N. , ALLAIN S. , HUMBERT M. 
Published: June 2009

SummaryA 22 Mn–0.6 C twinning induced plasticity steel with an average grain size of 2.6 μm was deformed in tension at room temperature. The electron backscattered diffraction technique was used to characterize the twinning structure in relation with the local texture evolution. For nanoscale analysis, additional transmission electron microscopy analysis was performed. Nanotwins were activated in the largest grains from the beginning of the deformation. They interacted with a well‐developed dislocation structure that induced detectable intragranular orientation variations. With increasing deformation, dense bundles of nanotwins preferentially developed in grains oriented close to the <111>//tensile direction fibre (promoted by the deformation) as well as medium to high angle sub‐boundaries. These key features of the twinned microstructure were finally related to the remarkably high strain hardening, which evolved according to different stages.
Chromatic two‐photon excitation fluorescence imaging
Authors: XU Q. , SHI K. , YIN S. , LIU Z. 
Published: June 2009

SummaryWe report on a chromatic axial scanning method for two‐photon excitation fluorescence imaging. Effective axial scanning is achieved by incorporating a Fresnel lens in the system, which has large chromatic aberration and can therefore focus the excitation beam to different axial positions depending on its wavelength. We experimentally demonstrated this technique and used it to image the cross‐section of fluorescent microspheres.
High‐aperture cryogenic light microscopy
Authors: LE GROS M.A. , McDERMOTT G. , UCHIDA M. , KNOECHEL C.G. , LARABELL C.A. 
Published: June 2009

SummaryWe report here the development of instruments and protocols for carrying out high numerical aperture immersion light microscopy on cryogenic specimens. Imaging by this modality greatly increases the lifetimes of fluorescence probes, including those commonly used for protein localization studies, while retaining the ability to image the specimen with high fidelity and spatial resolution. The novel use of a cryogenic immersion fluid also minimizes the refractive index mismatch between the sample and lens, leading to a more efficient coupling of the light from the sample to the image forming system. This enhancement is applicable to both fluorescence and transmitted light microscopy techniques. The design concepts used for the cryogenic microscope can be applied to virtually any existing light‐based microscopy technique. This prospect is particularly exciting in the context of ‘super‐resolution’ techniques, where enhanced fluorescence lifetime probes are especially useful. Thus, using this new modality it is now possible to observe dynamic events in a live cell, and then rapidly vitrify the specimen at a specific time point prior to carrying out high‐resolution imaging. The techniques described can be used in conjunction with other imaging modalities in correlated studies. We have also developed instrumentation to perform cryo‐light imaging together with soft X‐ray tomography on the same cryo‐fixed specimen as a means of carrying out high content, quantifiable correlated imaging analyses. These methods are equally applicable to correlated light and electron microscopy of frozen biological objects.
Live cell tracking based on cellular state recognition from microscopic images
Authors: SUN Y.‐N. , LIN C.‐H. , KUO C.‐C. , HO C.‐L. , LIN C.‐J. 
Published: June 2009

SummaryThe analysis of cell motion is an essential process in fundamental medical studies because most active cellular functions involve motion. In this paper, a computer‐assisted motion analysis system is proposed for cell tracking. In the proposed tracking process, unlike in conventional tracking methods, cellular states referring to the cellular life cycle are defined and appropriate strategies are adopted for cells at different states. The use of cellular state recognition allows detection of possible cell division and hence can improve the robustness of cell tracking. Experimental results show that cells can be successfully segmented and tracked over a long period of time, and the proposed system is found to be as accurate as manual tracking. Various quantitative analyses and visualizations are used to represent cell motion, which demonstrates the usefulness of the proposed system in the study of cell dynamics.
Continuous positive airway pressure treatment for obstructive sleep apnoea reduces resting heart rate but does not affect dysrhythmias: a randomised controlled trial
Authors: CRAIG SONYA , PEPPERELL JUSTIN C. T. , KOHLER MALCOLM , CROSTHWAITE NICKY , DAVIES ROBERT J. O. , STRADLING JOHN R. 
Published: June 2009

SummaryObstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and may precipitate cardiac dysrhythmias. Uncontrolled reports suggest that continuous positive airway pressure (CPAP) may reduce dysrhythmia frequency and resting heart rate. We undertook a randomised controlled trial of therapeutic CPAP and compared with a subtherapeutic control which included an exploration of changes in dysrhythmia frequency and heart rate. Values are expressed as mean (SD). Eighty‐three men [49.5 (9.6) years] with moderate–severe OSA [Oxygen Desaturation Index, 41.2 (24.3) dips per hour] underwent 3‐channel 24‐h electrocardiograms during normal daily activities, before and after 1 month of therapeutic (n = 43) or subtherapeutic (n = 40) CPAP. Recordings were manually analysed for mean heart rate, pauses, bradycardias, supraventricular and ventricular dysrhythmias. The two groups were well matched for age, body mass index, OSA severity, cardiovascular risk factors and history. Supraventricular ectopics and ventricular ectopics were frequently found in 95.2% and 85.5% of patients, respectively. Less common were sinus pauses (42.2%), episodes of bradycardia (12%) and ventricular tachycardias (4.8%). Compared with subtherapeutic control, CPAP reduced mean 24‐h heart rate from 83.0 (11.5) to 79.7 (9.8) (P < 0.002) in the CPAP group compared with a non‐significant rise (P = 0.18) from 79.0 (10.4) to 79.9 (10.4) in the subtherapeutic group; this was also the case for the day period analysed separately. There was no significant change in the frequencies of dysrhythmias after CPAP. Four weeks of CPAP therapy reduces mean 24‐h heart rate possibly due to reduced sympathetic activation but did not result in a significant decrease in dysrhythmia frequency.
Highway driving performance and cognitive functioning the morning after bedtime and middle‐of‐the‐night use of gaboxadol, zopiclone and zolpidem
Authors: LEUFKENS TIM R. M. , LUND JESPER S. , VERMEEREN ANNEMIEK 
Published: June 2009

SummaryGaboxadol is a selective extrasynaptic GABAA receptor agonist previously in development for the treatment of insomnia. Due to its short half‐life (1.5–2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle‐of‐the‐night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty‐eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double‐blind, placebo‐controlled, active‐referenced five‐way cross‐over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on‐the‐road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all‐subjects‐completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle‐of‐the‐night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.
Evidence for divergent natural selection of a Lake Tanganyika cichlid inferred from repeated radiations in body size
Authors: TAKAHASHI T. , WATANABE K. , MUNEHARA H. , RÜBER L. , HORI M. 
Published: June 2009

AbstractDivergent natural selection is thought to play a vital role in speciation, but clear, measurable examples from nature are still few. Among the many possible sources of divergent natural selection, predation pressure may be important because predators are ubiquitous in food webs. Here, we show evidence for divergent natural selection in a Lake Tanganyika cichlid,Telmatochromis temporalis, which uses burrows under stones or empty snail shells as shelters. This species contains normal and dwarf morphs at several localities. The normal morph inhabits rocky shorelines, whereas the dwarf morph invariably inhabits shell beds, where empty snail shells densely cover the lake bottom. Genetic evidence suggested that the dwarf morph evolved independently from the normal morph at two areas, and morphological analysis and evaluation of habitat structure revealed that the body sizes of morphs closely matched the available shelter sizes in their habitats. These findings suggest that the two morphs repeatedly evolved through divergent natural selection associated with the strategy for sheltering from predators.
How might infant and paediatric immune responses influence malaria vaccine efficacy?
Authors: MOORMANN A. M. 
Published: June 2009

SummaryNaturally acquired immunity to malaria requires repeat infections yet does not engender sterile immunity or long‐lasting protective immunologic memory. This renders infants and young children the most susceptible to malaria‐induced morbidity and mortality, and the ultimate target for a malaria vaccine. The prevailing paradigm is that infants initially garner protection due to transplacentally transferred anti‐malarial antibodies and other intrinsic factors such as foetal haemoglobin. As these wane infants have an insufficient immune repertoire to prevent genetically diverse Plasmodium infections and an inability to control malaria‐induced immunopathology. This Review discusses humoral, cell‐mediated and innate immune responses to malaria and how each contributes to protection – focusing on how deficiencies in infant and paediatric immune responses might influence malaria vaccine efficacy in this population. In addition, burgeoning evidence suggests a role for inhibitory receptors that limit immunopathology and guide the development of long‐lived immunity. Precisely how age or malaria infections influence the function of these regulators is unknown. Therefore the possibility that infants may not have the immune‐dexterity to balance effective parasite clearance with timely immune‐regulation leading to protective immunologic memory is considered. And thus, malaria vaccines tested in adults and older children may not be predictive for trials conducted in infants.
Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming ‘vaccine resistant malaria’
Authors: TAKALA S. L. , PLOWE C. V. 
Published: June 2009

SummaryThe development of effective malaria vaccines may be hindered by extensive genetic diversity in the surface proteins being employed as vaccine antigens. Understanding of the extent and dynamics of genetic diversity in vaccine antigens is needed to guide rational vaccine design and to interpret the results of vaccine efficacy trials conducted in malaria endemic areas. Molecular epidemiological, population genetic, and structural approaches are being employed to try to identify immunologically relevant polymorphism in vaccine antigens. The results of these studies will inform choices of which alleles to include in multivalent or chimeric vaccines; however, additional molecular and immuno‐epidemiological studies in a variety of geographic locations will be necessary for these approaches to succeed. Alternative means of overcoming antigenic diversity are also being explored, including boosting responses to critical conserved regions of current vaccine antigens, identifying new, more conserved and less immunodominant antigens, and developing whole‐organism vaccines. Continued creative application and integration of tools from multiple disciplines, including epidemiology, immunology, molecular biology, and evolutionary genetics and genomics, will likely be required to develop broadly protective vaccines against Plasmodium and other antigenically complex pathogens.
The development of the RTS,S malaria vaccine candidate: challenges and lessons
Authors: BALLOU W. R. 
Published: June 2009

SummaryRTS,S is the world’s most advanced malaria vaccine candidate and is intended to protect infants and young children living in malaria endemic areas of sub‐Saharan Africa against clinical disease caused by Plasmodium falciparum. Recently, a pivotal Phase III efficacy trial of RTS,S began in Africa. The goal of the programme has been to develop a vaccine that will be safe and effective when administered via the Expanded Program for Immunization (EPI) and significantly reduce the risk of clinically important malaria disease during the first years of life. If a similar reduction in the risk of severe malaria and other important co‐morbidities associated with malaria infection can be achieved, then the vaccine could become a major new tool for reducing the burden of malaria in sub‐Saharan Africa. Encouraging data from the ongoing phase II programme suggest that these goals may indeed be achievable. This review discusses some of the unique challenges that were faced during the development of this vaccine, highlights the complexity of developing new vaccine technologies and illustrates the power of partnerships in the ongoing fight against this killer disease.
Malaria vaccine trial endpoints – bridging the gaps between trial design, public health and the next generation of vaccines
Authors: O’MEARA W. P. , LANG T. 
Published: June 2009

SummaryA recent working group convened by the World Health Organization recommended that time to first or only episode of clinical malaria should be used to evaluate vaccine efficacy in phase III trials. However, calculating vaccine efficacy based on this endpoint misses important aspects of malaria disease and transmission. Here, we discuss the gaps that this approach leaves in predicting the potential public health impact of a vaccine and the challenges faced by vaccine trial designers. We examine the implications of current vaccine trial design on effectiveness studies and the next generation of malaria vaccines.
Acclimation of leaf hydraulic conductance and stomatal conductance of Pinus taeda (loblolly pine) to long‐term growth in elevated CO2 (free‐air CO2 enrichment) and N‐fertilization
Authors: DOMEC JEAN‐CHRISTOPHE , PALMROTH SARI , WARD ERIC , MAIER CHRIS A. , THÉRÉZIEN M. , OREN RAM 
Published: June 2009

ABSTRACTWe investigated how leaf hydraulic conductance (Kleaf) of loblolly pine trees is influenced by soil nitrogen amendment (N) in stands subjected to ambient or elevated CO2 concentrations (CO2a and CO2e, respectively). We also examined how Kleaf varies with changes in reference leaf water potential (Ψleaf‐ref) and stomatal conductance (gs‐ref) calculated at vapour pressure deficit, D of 1 kPa. We detected significant reductions in Kleaf caused by N and CO2e, but neither treatment affected pre‐dawn or midday Ψleaf. We also detected a significant CO2e‐induced reduction in gs‐ref and Ψleaf‐ref. Among treatments, the sensitivity of Kleaf to Ψleaf was directly related to a reference Kleaf (Kleaf‐ref computed at Ψleaf‐ref). This liquid‐phase response was reflected in a similar gas‐phase response, with gs sensitivity to D proportional to gs‐ref. Because leaves represented a substantial component of the whole‐tree conductance, reduction in Kleaf under CO2e affected whole‐tree water use by inducing a decline in gs‐ref. The consequences of the acclimation of leaves to the treatments were: (1) trees growing under CO2e controlled morning leaf water status less than CO2a trees resulting in a higher diurnal loss of Kleaf; (2) the effect of CO2e on gs‐ref was manifested only during times of high soil moisture.
Thermogenesis of three species of Arum from Crete
Authors: SEYMOUR ROGER S. , GIBERNAU MARC , PIRINTSOS STERGIOS ARG. 
Published: June 2009

ABSTRACTInflorescences of arum lilies have a three‐part spadix with a scent‐producing, sterile appendix above two bands of fertile male and female florets. The appendix and male florets are thermogenic, but with different temporal patterns. Heat‐production was measured in Arum concinnatum, A. creticum and A. idaeum. The male florets of A. concinnatum showed a 3 d continuous episode of thermogenesis with three waves, and the appendix warmed in a single, 6 h episode. Maximum fresh‐mass‐specific CO2 production rate was 0.17 µmol s−1 g−1 to achieve a 10.9 °C temperature elevation by the appendix, and 0.92 µmol s−1 g−1 to achieve a 4.8 °C elevation by male florets. Reversible, physiological temperature regulation was not evident in either tissue. Respiration increased with tissue temperatures with Q10 values of 1.8–3.9, rather than less than 1.0 as occurs in thermoregulatory flowers. Experimental step changes in temperature of appendix and male floret tissues also failed to show thermoregulatory responses. The patterns of thermogenesis therefore appear to be fixed by the temporal sequence of blooming. Thermogenesis in the alpine species, A. creticum and A. idaeum, was significantly lower than in the lowland A. concinnatum, possibly related to difficulty in raising floral temperature in their cold and windy habitat.