bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Portrait of a profession revisited’
Authors: Wilson Sir Richard 
Published: June 2003

On the walls of my private office hang the photographs of my seven distinguished predecessors as Secretary of the Cabinet. I sometimes find myself staring at them for inspiration, not always successfully I admit.A week or two ago I found myself looking at the great Lord Bridges, Secretary of the Cabinet and War Cabinet from 1938 to 1946. I wondered what he would have made of it if in the space of a week one of his predecessors had published an article in The Spectator advertised as ‘The Descent of the Civil Servant’ and another had appeared on the Frost programme to reassure the world that the Service was still in good shape.Both predecessors, Lords Butler and Armstrong, I hasten to say, were acting in the most supportive spirit and spoke from what for all of us is a deeply shared view of the role of the Civil Service. But, staring at Bridges, I could see a bubble emerging from his mouth enquiring: what precisely is happening on your watch, Sir Richard?
Advances in optical imaging of the newborn infant brain
Authors: Hebden Jeremy C. 
Published: June 2003

AbstractNew methods of imaging the oxygenation, hemodynamics, and metabolism of the newborn infant brain are being developed, based on illumination of the head with near‐infrared light. Techniques known as optical topography and optical tomography have the potential to provide valuable information about the function of the normal brain, and about a variety of cerebral pathology such as hypoxic‐ischemia. Optical methods provide a unique means of monitoring brain oxygenation safely in an intensive care environment without interference with the normal handling of the infant. Studies on infants have focused on the assessment of steady‐state regional cerebral perfusion and tissue oxygenation, as well as monitoring hemodynamic changes in response to sensory stimulation. Recent technological and methodological advances in this research field are reviewed, and the likely impact of optical imaging methods on the care of newborn infants is assessed.
Optical coherence tomography: Technology and applications for neuroimaging
Authors: Boppart Stephen A. 
Published: June 2003

AbstractOptical coherence tomography (OCT) is an emerging imaging technology with applications in biology, medicine, and materials investigations. Attractive features include high cellular‐level resolution, real‐time acquisition rates, and spectroscopic feature extraction in a compact noninvasive instrument. OCT can perform “optical biopsies” of tissue, producing images approaching the resolution of histology without having to resect and histologically process tissue specimens for characterization and diagnosis. This article will review several of the current technological developments in OCT. To illustrate the potential of this technology for neuroimaging, applications for imaging neural development, the neural retina, tumors of the central nervous system, and the microsurgical repair of peripheral nerves will be presented. This technology offers a potential investigative tool for addressing many of the present challenges in neuroimaging.
Optimum filtering for EROS measurements
Authors: Maclin Edward L. , Gratton Gabriele , Fabiani Monica 
Published: June 2003

AbstractThe event‐related optical signal (EROS) is a relatively new technology that provides noninvasive data about the time course of neural activity in circumscribed cortical areas. However, much still remains to be learned about the physiology and physics underlying the observed signals. We examined the instrumental and physiological noise observed in the intensity modulation and phase‐delay measurements produced by a frequency domain oxymeter in response to steady‐state auditory stimuli. We present here data on the effects of different filters on the between‐subjects response consistency for amplitude and phase measurements. The results of these analyses may help explain some apparently discrepant results previously reported from different laboratories (Steinbrink et al., 2000), and illustrate differences between data from different types of measurements.
Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near‐infrared optical imaging
Authors: Franceschini Maria Angela , Fantini Sergio , Thompson John H. , Culver Joseph P. , Boas David A. 
Published: June 2003

AbstractWe have performed a noninvasive bilateral optical imaging study of the hemodynamic evoked response to unilateral finger opposition task, finger tactile, and electrical median nerve stimulation in the human sensorimotor cortex. This optical study shows the hemoglobin‐evoked response to voluntary and nonvoluntary stimuli. We performed measurements on 10 healthy volunteers using block paradigms for motor, sensory, and electrical stimulations of the right and left hands separately. We analyzed the spatial/temporal features and the amplitude of the optical signal induced by cerebral activation during these three paradigms. We consistently found an increase (decrease) in the cerebral concentration of oxy‐hemoglobin (deoxy‐hemoglobin) at the cortical side contralateral to the stimulated side. We observed an optical response to activation that was larger in size and amplitude during voluntary motor task compared to the other two stimulations. The ipsilateral response was consistently smaller than the contralateral response, and even reversed (i.e., a decrease in oxy‐hemoglobin, and an increase in deoxy‐hemoglobin) in the case of the electrical stimulation. We observed a systemic contribution to the optical signal from the increase in the heart rate increase during stimulation, and we made a first attempt to subtract it from the evoked hemoglobin signal. Our findings based on optical imaging are in agreement with results in the literature obtained with positron emission tomography and functional magnetic resonance imaging.
The mind's eye, looking inward? In search of executive control in internal attention shifting
Authors: Gehring William J. , Bryck Richard L. , Jonides John , Albin Roger L. , Badre David 
Published: June 2003

AbstractIn studies of mental counting, participants are faster to increment a count that was just incremented (no‐switch trial) than to increment a different count (switch trial). Investigators have attributed the effect to a shift in the internal focus of attention on switch trials. Here we report evidence for other bottom‐up and top‐down contributions. Two stimuli were mapped to each of two counts. The no‐switch facilitation was greater when stimuli repeated than when they were different. Event‐related potential (ERP) activity associated with repetitions was anterior to that associated with switching. Runs of no‐switch trials elicited faster responses and frontal ERP activity. Runs of switches and large counts both elicited slow responses and reduced P300 amplitudes. Bottom‐up processes may include priming on no‐switch trials and conflict on switch trials. Top‐down processes may control conflict, subvocal rehearsal, and the contents of working memory.
Circadian rhythm and desensitization in chemosensory event‐related potentials in response to odorous and painful stimuli
Authors: Nordin Steven , Lötsch Jörn , Murphy Claire , Hummel Thomas , Kobal Gerd 
Published: June 2003

AbstractOlfactory (H2S) and trigeminal (CO2) event‐related potentials (ERPs) were studied with respect to circadian rhythm and desensitization. ERPs, perceived odor and pain intensity, oral temperature, blood pressure, heart rate, nasal volume, and sleepiness were assessed four times at 04:00, 08:00, 12:00, 16:00, 20:00, and 24:00 hr in five young men. For each of these 24 sessions per participant, H2S and CO2 were each presented in 15 series of five stimuli with a 5‐s ISI within and 30‐s ISI between series. ERP amplitudes, but not latencies, followed a circadian rhythm (largest at 16:00 and smallest at 04:00) similar to oral temperature and opposite to sleepiness. Amplitudes decreased (most pronounced at 16:00 and 20:00) and latencies increased with repeated stimulation, suggesting desensitization, in accordance with odor and pain intensity. These findings imply that circadian rhythm and desensitization should be considered in chemosensory ERP studies.
Reliability of smooth pursuit, fixation, and saccadic eye movements
Authors: Ettinger Ulrich , Kumari Veena , Crawford Trevor J. , Davis Robert E. , Sharma Tonmoy , Corr Philip J. 
Published: June 2003

AbstractThe present study investigated the reliability and susceptibility to practice effects of oculomotor tasks. Smooth pursuit, fixation, antisaccade, and prosaccade tasks were administered to 31 healthy participants to assess internal consistency (Cronbach's alpha) and within‐session practice effects. Twenty‐one of these participants were retested after an average interval of 57.86 days to assess temporal stability and between‐session practice effects. Internal consistencies were high for most measures, with few within‐session performance changes. Test–retest reliabilities of most measures were good. Between‐session practice effects were most consistently observed on the antisaccade task, indicated by reduced error rate and improved spatial accuracy at retest. Magnitude of improvement on these measures was related to performance, indicating that poor performers benefited most from repeated assessment. These findings support the trait nature of oculomotor function and point to the need to take into consideration between‐session practice effects on the antisaccade task in longitudinal studies.
Democracy's Performance
Authors: McKenzie Jon 
Published: June 2003

McKenzie asks, “If the ancient Greeks invented democracy in the form of the city-state, and colonial North Americans reinvented it in the nation-state, what democratic forms might the world create in the age of global performance?” He explores this question in relation to the thought of Nietzsche and Marcuse—and in terms of “dissatisfied democrats”: people who strongly believe in democracy but are unhappy with its particular embodiments. Could it be that democracy is an inherently incomplete project, one that is always “to come,” always being invented, always being tested and contested, always being asked to perform? The Electronic Disturbance Theater demonstrates how the Internet can be used to facilitate social and political engagement and protest. Dubbed “virtual Zapatistas” because of its strong support for the liberation movement in Mexico and throughout Latin America, EDT's actions combine the political struggle for indigenous self-determination with a critique of neoliberalism aka globalization. In the articles and interview that follow, EDT's origins, development, and ongoing actions are examined. You are invited to participate.
Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1
Authors: Lahav Judith , Wijnen Eveline M. , Hess Oded , Hamaia Samir W. , Griffiths Delia , Makris Michael , Knight C. Graham , Essex David W. , Farndale Richard W. 
Published: June 2003

AbstractIntegrin α2β1 is the principal adhesive receptor for collagen but platelets also adhere through glycoprotein VI (GPVI). Integrin αIIbβ3 may augment platelet adhesion. We have shown that disulfide exchange is necessary for platelet adhesion to fibrinogen, fibronectin, and collagen. However 2 questions remained: (1) Can activated αIIbβ3 explain the observed role of disulfide exchange in adhesion to collagen, or is this role common to other integrins? (2) Is disulfide dependence specific to the integrin receptors or shared with GPVI? To discriminate adhesive functions of α2β1 from those of αIIbβ3 we used Glanzmann platelets and αIIbβ3-specific antibodies applied to normal platelets. To resolve adhesive events mediated by α2β1 from those of GPVI we used synthetic peptides specific to each receptor. We addressed direct integrin ligation using purified α2β1 and recombinant I domain. We observed the following: adhesion to the α2β1-specific peptide was disulfide-exchange dependent and protein disulfide isomerase (PDI) mediated; membrane-impermeant thiol blockers inhibited α2β1, but not GPVI mediated, adhesion; direct blockade of PDI revealed that it is involved in adhesion through α2β1 but not GPVI; and purified α2β1, but not recombinant I domain, depended on free thiols for ligation. These data suggest that the enzymatically catalyzed adhesion-associated reorganization of disulfide bonds is common to members of the integrin family and specific to this family.
Leukemia in twins: lessons in natural history
Authors: Greaves Mel F. , Maia Ana Teresa , Wiemels Joseph L. , Ford Anthony M. 
Published: June 2003

AbstractIdentical infant twins with concordant leukemia were first described in 1882, and since that time many such pairs of infants and older children have been described. It has long been recognized that this situation offers a unique opportunity to identify aspects of the developmental timing, natural history, and molecular genetics of pediatric leukemia in general. We reviewed both the older literature and more recent molecular biologic studies that have uncovered the basis of concordance of leukemia. Molecular markers of clonality, including unique, genomic fusion gene sequences, have provided unequivocal evidence that twin pairs of leukemia have a common clonal origin. The only plausible basis for this, first suggested more than 40 years ago, is that following initiation of leukemia in one twin fetus, clonal progeny spread to the co-twin via vascular anastomoses within a single, monochorionic placenta. This explanation has been endorsed by the identification of clonotypic gene fusion sequences in archived neonatal blood spots of individuals who subsequently developed leukemia. These analyses of twin leukemias have thrown considerable light on the natural history of disease. They reveal a frequent prenatal origin and an early or initiating role for chromosome translocations. Further, they provide evidence for a variable and often protracted latency and the need, in childhood acute lymphoblastic leukemia (ALL)/acute myeloblastic leukemia (AML), for further postnatal exposures and/or genetic events to produce clinical disease. We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms. (Blood. 2003;102:2321-2333)
Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-γ
Authors: Rubio Marie-Therese , Kim Yong-Mi , Sachs Teviah , Mapara Markus , Zhao Guiling , Sykes Megan 
Published: June 2003

AbstractSome patients lose chimerism following nonmyeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-versus-graft (HVG) alloresponses might induce antitumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLIs) to mixed chimeras established with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2a)→B6 (H2b) strain combination using depleting anti–T-cell monoclonal antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia cells (MMB3.19) were administered 7 days following donor lymphocyte infusion (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft-versus-hostdisease (GVHD) following DLI, whereas RLI led to loss of chimerism. Both RLI and DLI significantly delayed tumor mortality. In another strain combination (B10.BR [H2k]→BALB/c [H2d]), RLI-induced or spontaneous loss of chimerism was associated with antitumor effects against the host-type B-cell lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced elevated serum interferon-γ (IFN-γ) levels, and recipient-derived IFN-γ was critical for their antitumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate antitumor effects against hematologic malignancies via a recipient-derived IFN-γ–mediated mechanism. A novel approach to achieving anti-tumor effects without the risk of GVHD is suggested.
Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development
Authors: Wertheim Jason A. , Perera Samanthi A. , Hammer Daniel A. , Ren Ruibao , Boettiger David , Pear Warren S. 
Published: June 2003

AbstractWe have previously found that P210BCR-ABL increases the adhesion of hematopoietic cell lines to fibronectin by a mechanism that is independent of tyrosine kinase activity. To investigate the pathway(s) by which P210BCR-ABL influences cell adhesion, we used a quantitative cell adhesion device that can discern small changes in cell adhesion to assay P210BCR-ABL with mutations in several critical domains. We expressed P210BCR-ABL mutants in 32D myeloblast cells and found that binding to fibronectin is mediated primarily by the α5β1 integrin. We performed a structure/function analysis to map domains important for cell adhesion. Increased adhesion was mediated by 3 domains: (1) the N-terminal coiled-coil domain that facilitates oligomerization and F-actin localization; (2) bcr sequences between aa 163 to 210; and (3) F-actin localization through the C-terminal actin-binding domain of c-abl. We compared our adhesion results with the ability of these mutants to cause a chronic myelogenous leukemia (CML)–like disease in a murine bone marrow transplantation assay and found that adhesion to fibronectin did not correlate with the ability of these mutants to cause CML. Together, our results suggest that F-actin localization may play a pivotal role in modulating adhesion but that it is dispensable for the development of CML.
Most lymphoid organ dendritic cell types are phenotypically and functionally immature
Authors: Wilson Nicholas S. , El-Sukkari Dima , Belz Gabrielle T. , Smith Christopher M. , Steptoe Raymond J. , Heath William R. , Shortman Ken , Villadangos José A. 
Published: June 2003

AbstractDendritic cells (DCs) have been thought to follow a life history, typified by Langerhans cells (LCs), with 2 major developmental stages: an immature stage that captures antigens in the periphery and a mature stage that presents those antigens in the lymphoid organs. However, a systematic assessment of the maturity of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs from peripheral tissues were mature and therefore could not process and present newly encountered antigens. However, all the other DC types were phenotypically and functionally immature: they expressed low levels of surface major histocompatibility complex class II (MHC II) and CD86, accumulated MHC II in their endosomes, and could present newly encountered antigens. These immature DCs could be induced to mature by culture in vitro or by inoculation of inflammatory stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ.
Analysis of intracellular storage and regulated secretion of 3 von Willebrand disease–causing variants of von Willebrand factor
Authors: Michaux Grégoire , Hewlett Lindsay J. , Messenger Sarah L. , Goodeve Anne C. , Peake Ian R. , Daly Martina E. , Cutler Daniel F. 
Published: June 2003

AbstractThe rapid exocytosis of von Willebrand factor (VWF) in response to vascular injury can be attributed to the fact that VWF is stored in the Weibel-Palade bodies (WPBs) of endothelial cells. We describe a system for examining the ability of VWF to drive both the formation of a storage compartment and the function of that compartment with respect to regulated secretion. Transient transfection of HEK293 cells with wild-type human VWF cDNA leads to the formation of numerous elongated organelles that resemble WPBs. These “pseudo-WPBs” exhibit the internal structure, as well as the ability to recruit membrane proteins including P-selectin, of bona fide WPBs. Finally, VWF was efficiently secreted upon stimulation by phorbol ester. We used this system to examine 3 VWF mutations leading to von Willebrand disease that affect VWF multimerization and constitutive secretion. Surprisingly we find that all 3 mutants can, to some extent, make pseudo-WPBs that recruit appropriate membrane proteins and that are responsive to secretagogues. The most striking defects are a delay in formation and a reduction in the length and number of pseudo-WPBs in proportion to the clinical severity of the mutation. Studies of pseudo-WPB formation in this system thus yield insights into the structure-function relationships underpinning the ability of VWF to form functional WPBs. (Blood. 2003;102:2452-2458)
A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation
Authors: Bozza Silvia , Perruccio Katia , Montagnoli Claudia , Gaziano Roberta , Bellocchio Silvia , Burchielli Emanuela , Nkwanyuo Gabriel , Pitzurra Lucia , Velardi Andrea , Romani Luigina 
Published: June 2003

AbstractDendritic cells (DCs) have a remarkable functional plasticity in response to conidia and hyphae of the fungus Aspergillus fumigatus. In the present study we sought to assess the capacity of DCs activated by live fungi or fungal RNA to generate antifungal immunity in vivo. We found that both human and murine DCs pulsed with live fungi or transfected with fungal RNA underwent functional maturation, as revealed by the up-regulated expression of histocompatibility class II antigen and costimulatory molecules and the production of interleukin 12 (IL-12) in response to conidia or conidial RNA and of IL-4/IL-10 in response to hyphae or hyphal RNA. DCs pulsed with conidia or transfected with conidial RNA activated antigen-specific, interferon γ (IFN-γ)-producing T lymphocytes in vitro and in vivo on adoptive transfer in mice otherwise susceptible to aspergillosis. TH1-dependent antifungal resistance could also be induced in mice receiving allogeneic bone marrow transplants and was associated with an accelerated recovery of myeloid and lymphoid cells. Because the efficacy of the infusion of DCs was superior to that obtained on the adoptive transfer of Aspergillus-specific T cells, these results indicate the vaccinating potential of DCs pulsed with Aspergillus conidia or conidial RNA in hematopoietic transplantation. (Blood. 2003;102:3807-3814)