bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death
Authors: Serra Sara , Horenstein Alberto L. , Vaisitti Tiziana , Brusa Davide , Rossi Davide , Laurenti Luca , D'Arena Giovanni , Coscia Marta , Tripodo Claudio , Inghirami Giorgio , Robson Simon C. , Gaidano Gianluca , Malavasi Fabio , Deaglio Silvia 
Published: October 2011

Abstract
Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67+ CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/CD73+ CLL cells generate ADO from ADP in a time- and concentration-dependent manner. In peripheral blood, CD73 expression occurs in 97/299 (32%) CLL patients and pairs with CD38 and ZAP-70 expression. CD73-generated extracellular ADO activates type 1 purinergic A2A receptors that are constitutively expressed by CLL cells and that are further elevated in proliferating neoplastic cells. Activation of the ADO receptors increases cytoplasmic cAMP levels, inhibiting chemotaxis and limiting spontaneous drug-induced apoptosis of CLL cells. These data are consistent with the existence of an autocrine adenosinergic loop, and support engraftment of leukemic cells in growth-favorable niches, while simultaneously protecting from the action of chemotherapeutic agents.
Chemistry and haematology sample rejection and clinical impact in a tertiary laboratory in Cape Town
Authors: Jacobsz Lourens A. , Zemlin Annalise E. , Roos Mark J. , Erasmus Rajiv T. 
Published: October 2011

AbstractRecent publications report that up to 70% of total laboratory errors occur in the pre-analytical phase. Identification of specific problems highlights pre-analytic processes susceptible to errors. The rejection of unsuitable samples can lead to delayed turnaround time and affect patient care.A retrospective audit was conducted investigating the rejection rate of routine blood specimens received at chemistry and haematology laboratories over a 2-week period. The reasons for rejection and potential clinical impact of these rejections were investigated. Thirty patient files were randomly selected and examined to assess the impact of these rejections on clinical care.A total of 32,910 specimens were received during the study period, of which 481 were rejected, giving a rejection rate of 1.46%. The main reasons for rejection were inappropriate clotting (30%) and inadequate sample volume (22%). Only 51.7% of rejected samples were repeated and the average time for a repeat sample to reach the laboratory was about 5 days (121 h). Of the repeated samples, 5.1% had results within critical values. Examination of patient folders showed that in 40% of cases the rejection of samples had an impact on patient care.The evaluation of pre-analytical processes in the laboratory, with regard to sample rejection, allowed one to identify problem areas where improvement is necessary. Rejected samples due to factors out of the laboratory’s control had a definite impact on patient care and can thus affect customer satisfaction. Clinicians should be aware of these factors to prevent such rejections.
‘Seeing tunes.’ The role of visual gestures in tune interpretation
Authors: Borràs-Comes Joan , Prieto Pilar 
Published: October 2011

AbstractOne of the unresolved questions in audiovisual prosody is the relative contribution of acoustic and visual cues to the expression of prosodic meaning. Though the majority of studies on audiovisual prosody have found a complementary mode of processing whereby sight provides relatively weak and redundant information in comparison with strong auditory cues, other work has found that sight provides information more efficiently than hearing. In Catalan, a pitch range contrast in a rising-falling nuclear configuration conveys a difference between a contrastive focus statement and an echo question. The main goal of this study is to investigate the relative contribution of visual cues in conveying this distinction. Twenty native speakers of Central Catalan participated in two identification tasks in which they had to decide between a focus statement and a question interpretation. Experiment 1 used a pitch range auditory continuum combined with two congruent and incongruent videotapes showing the facial gestures that are characteristic of the two pragmatic meanings. Experiment 2 used the same auditory continuum in combination with another continuum for facial gestures produced using a digital image-morphing technique. The responses and reaction times obtained in both experiments revealed a consistent reliance on visual cues in the listener's decisions, but also a consistent effect of the auditory stimulus. We argue that although facial gestures are the most influential elements that Catalan listeners rely on to decide between contrastive focus and echo question interpretations, bimodal integration with the acoustic cues is necessary for perceptual processing to be accurate and fast. Finally, we discuss the implications of these results for models of audiovisual processing.
ASL sign lowering as undershoot: A corpus study
Authors: Russell Kevin , Wilkinson Erin , Janzen Terry 
Published: October 2011

AbstractAmerican Sign Language (ASL) signs that are located on the forehead in their canonical form are often articulated lower during natural signing. Previous studies have examined this phenomenon from a phonetic perspective, treating it as a form of undershoot, and from a variationist sociolinguistic perspective, treating it as a categorical process. This study sees if the findings and explanations of these studies can be extended to the lowering of signs formed in locations other than the forehead. In a corpus of natural conversational signing from six signers, we measure the vertical displacement of over 3000 tokens of signs canonically formed at the face, head, or neck. While there is some apparent evidence for a categorical lowering process in a minority of signs and considerable evidence for undershoot, neither alone can explain the full range of displacement patterns across all signs and locations. Undershoot must be carefully planned and controlled: no matter how sloppy the signing, signers systematically avoid contacting their eyes. The results can be explained if there is a somatosensory forward-modelling mechanism that can veto undesirable gestural scores and whose decisions are incorporated during learning into the phonological distributions representing the locations of signs.
Dynamical account of how /b, d, g/ differ from /p, t, k/ in Spanish: Evidence from labials
Authors: Parrell Benjamin 
Published: October 2011

AbstractThis study examines articulatory lenition of intervocalic stops in Spanish and tests the theories that 1) /b, d, g/ have an intended target for closure equal to that of /p, t, k/ and 2) spirantization of /b, d, g/ is caused by undershoot due to their short duration phrase medially. Consistent with past acoustic studies, subjects produce /b/ with incomplete closure phrase medially and complete closure phrase initially. Additionally, /b/ is shorter than /p/ phrase medially though not initially. For /b/, though not for /p/, there is a correlation between constriction degree and duration, consistent with the theory of dynamical undershoot. The results from the study are accurately modeled with a virtual target for /b/ slightly beyond the point of articulator contact. Such a target results in full closure at long durations (such as found phrase initially) and incomplete closure at shorter durations. Based on this evidence, it is proposed that /b, d, g/ differ from /p, t, k/ in three ways: they are shorter, lack a devoicing gesture, and have a target closer to – but still beyond – the point of articulator contact.
Towards a gestural characterization of liquids: Evidence from Spanish and Russian
Authors: Proctor Michael 
Published: October 2011

AbstractThe production of intervocalic liquid consonants by five speakers of Spanish and four speakers of Russian was examined using ultrasound. Liquids in both languages were found to be united by a lower susceptibility to vocalic coarticulation than coronal obstruents produced in the same environments. Tongue body articulation in the Spanish lateral resembled that of a mid-front vowel; dorsal posture in the Spanish trill resembled that of a mid-back vowel. Tongue body articulation in Russian non-palatalized laterals resembled that of a mid-back vowel, and Russian non-palatalized trills were produced with a dorsal posture resembling that of a mid-central vowel.These results are consistent with the hypothesis that coronal liquid consonants consist of a consonant-like coronal component and an intrinsic vowel-like dorsal component (Delattre and Freeman, Linguistics 44: 29– 68, 1968; Sproat and Fujimura, Journal of Phonetics 21: 291–311, 1993). Liquid segments are modeled as recurrent stable constellations in which a tongue-tip gesture is coordinated with a tongue-body gesture (Browman and Goldstein, Gestural syllable position effects in American English, AIP Press, 1995). Differences between ‘clear’ and ‘pharyngealized’ liquids are attributed to differences in dorsal target locations. Rhotic allophony is argued to result from the interaction of articulatory and aerodynamic factors. Spanish liquid vocalization is modeled as lenition of tongue tip gestures, and Slavic liquid metathesis as a change in intergestural coupling relationships.
Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans
Authors: Marcus-Gueret Nancy , Schmidt Kristopher L , Stringham Eve G 
Published: October 2011

Abstract
The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor, the Rac/Rho GEF UNC-73/TRIO operates in both pathways, as isoform specific alleles exhibit enhancement of the phenotype in double-mutant combination with either unc-53 or vab-8. On the basis of these results, we propose a bipartite model for UNC-73/TRIO activity in excretory canal extension: a cell autonomous function that is mediated by the Rho-specific GEF domain of the UNC-73E isoform in conjunction with UNC-53 and UNC-71 and a cell nonautonomous function that is mediated by the Rac-specific GEF domain of the UNC-73B isoform, through partnering with VAB-8 and the receptors SAX-3 and EVA-1.
Emlődaganatos betegek primer szisztémás terápiája során elért eredményeink (2007–2010)
Authors: Zapf István , Tizedes György , Pavlovics Gábor , Kovács Gyula , Kálmán Endre , Szalai Gábor , Kövér Erika , Farkas Róbert , Horváth Örs Péter 
Published: October 2011

AbsztraktBevezetés:A műtét előtti onkológiai kezelés az előrehaladott emlőrákok mellett az utóbbi években a primeren operábilis esetekben is egyre nagyobb teret hódít. Retrospektív vizsgálatunk célja volt a primer szisztémás terápián (PST) átesett emlőtumoros betegek radiológiai és szövettani leleteinek kiértékelése az alkalmazott sebészi kezelés tükrében.Anyag és módszerek:Klinikánkon 2007 márciusa és 2010 januárja között 114 esetben előzte meg preoperatív kemoterápia az emlőműtétet, ebből 22 esetben a kezelés indikációja lokális irresecabilitas volt. 92 esetben az onkoteam a beteg fiatal kora, magas gradusú daganat vagy axillaris nyirokcsomó-metastasis miatt döntött a PST mellett. A betegek 6 ciklus 5-Fluorouracil-Epirubicin-Cyclophosphamid vagy Taxotere-Epirubicin kezelésben részesültek, melyet radiológiai kontroll, majd műtét követett. Vizsgálatainkban a preoperatív staging eredményeket hasonlítottuk össze a műtéti specimenből meghatározott patológiai staging eredményekkel.Eredmények:A PST után az operált betegek 17%-nál komplett, 21%-nál jelentős, míg 43%-nál mérsékelt regressziót értünk el. A preoperatív kezelésre 19%-uk nem reagált. A feldolgozás során észlelt T és N stádiumok csökkenése nem minden esetben korrelált egymással, illetve a PST-re adott radiológiai és hisztológiai válasz is eltérő volt.Konklúzió:Az alkalmazott PST a daganat méretének csökkentésére kifejezetten hatásosnak bizonyult, de a nyirokcsomóstátusz változása tekintetében kevésbé volt hatásos. A residualis DCIS miatt gyakran nem tudjuk annyira csökkenteni a resectio volumenét, mint amennyire a daganat méretének csökkenése azt megengedné.
Philosophy of … Philosophy and …: Taking the Conditions We Find Ourselves in Seriously
Authors: Smeyers Paul , Zahir Amrita 
Published: October 2011

Starting from Peters' characterization of philosophy of education, the article elaborates the development offered by the Blackwell Guide (i.e. a field of study that involves a variety of approaches, including philosophical analysis with problems rooted in the use of language in educational discourse, addressing the assumptions and values embedded in other disciplinary approaches in the study of education, and exploring what education might be or might become). Taking into account recent developments of educational research, it is argued that room should be made for other forms of study than empirical, be it quantitative or qualitative types of research. A critical discussion of the preoccupation with method — as well as more generally in educational research, in philosophy of education in particular — is offered. It is argued that the conditions we find ourselves in today, for example the demand for performativity in educational contexts, should be taken seriously and that this has implications for what we address in philosophy of education. Applying Sidorkin's ontological concept of dialogue, this reply extends Smeyers' argument that explorations in philosophy of education are insufficiently related to educational issues and to non-philosopher audiences, something that needs to occur in order for philosophers of education to escape from becoming extinct in the current climate of performativity, by focusing on how philosophers of education should bring together interest and substance to inform problems of policy and practice in education in a less monological way.
From the Scientistic to the Humanistic in the Construction of Contemporary Educational Knowledge
Authors: Bridges David , Thompson Christiane 
Published: October 2011

The starting point for this article is a lecture given fifty years ago by C.P. Snow under the title ‘The Two Cultures and the Scientific Revolution’, in which Snow critiques what he sees as the damaging intellectual division between the arts and humanities on the one side and the sciences on the other. Fifty years later this problem is, perhaps, better considered in terms of the hegemony of science, or, more accurately, in terms of a very restricted notion of science which the author refers to as ‘scientism’. Scientism privileges a very narrow empiricist view of science and in particular experimental methods which allow the measurement of physical and, by extension, human and social phenomena. The article illustrates a number of ways in which such scientism operates to exclude alternative perspectives on experience rooted in the humanities from social and educational enquiry and discourse. It challenges scientism in two ways. First, it argues that it represents an impoverished view of science itself, which, properly understood, draws on a much wider range of methods and methodologies, some of which bring it much closer to humanistic forms of enquiry than the narrow empiricism that is popularly advanced as its defining characteristic. Then the article begins to illustrate, more positively, the sort of contributions to educational understanding that draw essentially from the academic traditions of the humanities. These include: (i) the exploration of human conscious experience and intentionality; (ii) narratives (including auto/biography); (iii) descriptive writing; (iv) normativity; (v) literary, perhaps even ‘romantic’, sensibility. In this reply, the statement by David Bridges that scientism has taken hold of educational inquiry today is critically discussed. While it is argued that standardisation of educational research indeed brings about problematic consequences, it is also shown that the dichotomy of scientism and humanist perspective — as Bridges uses it — comes up short it terms of describing the current state of affairs. Referring to an announcement from the German Ministry of Education, it is demonstrated that the usage of the term ‘evidence’ is not evident in the context of standardised research: educational philosophy has to analyze the social contexts in which educational knowledge is fabricated. Generally it is necessary to employ plural research strategies in order not to reduce educational reality and the perspective that we have of it.
Philosophy of Education: A Thorn in the (Clay) Foot of the Educational System
Authors: Soëtard Michel , Casale Rita 
Published: October 2011

The article tries to defend the thesis that our educational systems are not doing well (which is not at all original), that the philosophy of education, more often than not, accompanies, justifies and reinforces the malaise of the system (which is already more original), and that it should, without a doubt, question itself in order to know how to support the betterment of education in our societies in crisis. The author tries to show how far the arguments supported by Soëtard — despite their critical attitude and purpose — may in a certain sense be compatible after all with the situation of the philosophy of education and even more with the situation of the educational system. Finally, the author suggests an alternative to Soëtard's philosophy of education: where Soëtard speaks of a philosophie de l'action pédagogique, the author prefers to speak of a philosophy of education as a critique.
Philosophy and the Rationalisation of Educative Action: The Example of Personal Autonomy
Authors: Foray Philippe , Maxwell Bruce 
Published: October 2011

In France, the philosophy of education is not accustomed to reflect on the concept of the ‘education system’. Often, the ‘humanistic’ purposes that it gives to education are far away from the real goals of a systematic education. Often also, it is confined to a critical attitude, whose constructive side is missing. Which form of philosophical practice is desirable vis-à-vis the transformations of the education systems? How to develop an at the same time normative and critical thought, which take account of the current evolutions? This is what this contribution is concerned with, using the limited example of personal autonomy. In this reply to Philippe Foray's article ‘Philosophy and the Rationalisation of Educative Action’, the author salutes Foray's call to anchor the project of articulating aims of education in the realities of contemporary education but claims that Foray's plea to re-imagine the philosophy of education is arbitrarily restricted. The notion that defending high-level directives should preoccupy educational philosophy is rejected. Far from characterising educational philosophy prior to mass, state-managed educational systems, the author argues, a more faithful rendering of the history of the field demonstrates that the responsibility of stating education's ends was largely imposed on educational philosophy by the rationalisation of educational systems itself. In conclusion, contemporary practical ethics is advanced as a model for a more expansive conception of educational philosophy's potential contribution to educational research, policy and practice.
Islet Cholesterol Accumulation Due to Loss of ABCA1 Leads to Impaired Exocytosis of Insulin Granules
Authors: Kruit Janine K. , Wijesekara Nadeeja , Fox Jocelyn E. Manning , Dai Xiao-Qing , Brunham Liam R. , Searle Gavin J. , Morgan Garry P. , Costin Adam J. , Tang Renmei , Bhattacharjee Alpana , Johnson James D. , Light Peter E. , Marsh Brad J. , MacDonald Patrick E. , Verchere C. Bruce , Hayden Michael R. 
Published: October 2011

OBJECTIVE
The ATP-binding cassette transporter A1 (ABCA1) is essential for normal insulin secretion from β-cells. The aim of this study was to elucidate the mechanisms underlying the impaired insulin secretion in islets lacking β-cell ABCA1.

RESEARCH DESIGN AND METHODS
Calcium imaging, patch clamp, and membrane capacitance were used to assess the effect of ABCA1 deficiency on calcium flux, ion channel function, and exocytosis in islet cells. Electron microscopy was used to analyze β-cell ultrastructure. The quantity and distribution of proteins involved in insulin-granule exocytosis were also investigated.

RESULTS
We show that a lack of β-cell ABCA1 results in impaired depolarization-induced exocytotic fusion of insulin granules. We observed disturbances in membrane microdomain organization and Golgi and insulin granule morphology in β-cells as well as elevated fasting plasma proinsulin levels in mice in the absence of β-cell ABCA1. Acute cholesterol depletion rescued the exocytotic defect in β-cells lacking ABCA1, indicating that elevated islet cholesterol accumulation directly impairs granule fusion and insulin secretion.

CONCLUSIONS
Our data highlight a crucial role of ABCA1 and cellular cholesterol in β-cells that is necessary for regulated insulin granule fusion events. These data suggest that abnormalities of cholesterol metabolism may contribute to the impaired β-cell function in diabetes.