bluuebunny/crossref_metadata_2025 huggingface dataset:
Conflicting views on court interpreting examined through surveys of legal professionals and court interpreters
Authors: Lee Jieun
Published: April 2009

This survey-based study examined the views of 226 legal professionals and 36 interpreting practitioners in Australia with respect to the role of the court interpreter and the quality of interpreting and revealed a statistically significant gap between the perceptions of the two professional groups. Both groups, however, were ambivalent in relation to some practical aspects of court interpreting, such as cultural intervention and the reproduction of speech style. The findings indicate that legal professionals generally held a favourable view of the overall quality of court interpreting. Both groups supported specialist certification for court interpreters.
Evolution of language with spatial topology
Authors: Chio Cecilia Di , Chio Paolo Di
Published: April 2009

In this paper, we propose two agent-based simulation models for the evolution of language in the framework of evolutionary language games. The theory of evolutionary language games arose from the union of evolutionary game theory, introduced by the English biologist John Maynard Smith, and language games, developed by the Austrian philosopher Ludwig Wittgenstein. The first model proposed is based on Martin Nowak’s work and is designed to reproduce and verify (or refute) the results Nowak obtained in his simplest mathematical model. For the second model, we extend the previous one with the introduction of a world where the languages live and evolve, and which influences interactions among individuals. The main goal of this research is to present a model which shows how the presence of a topological structure influences the communication among individuals and contributes to the emergence of clusters of different languages.
AAVE/creole copula absence
Authors: Sharma Devyani , Rickford John R.
Published: April 2009

This study confirms the robustness of the finding in the literature on African American Vernacular English (AAVE) and creole English (especially in the Caribbean) that omission of copular and auxiliary be varies systematically according to predicate type. Verbal predicates are associated with the highest rates of copula absence and following NPs with the lowest rates; following adjectives or locatives show intermediate rates (see Rickford 1998:190). Although this pattern is highly consistent, convincing explanations for it remain elusive. A recurrent suggestion (McWhorter 2000; Winford 1998, 2004; Wolfram 2000) is that the AAVE and creole English pattern is inherited independently from general processes of imperfect second language learning (simplification, generalization) that operated as the African ancestors of today’s speakers acquired English. In this paper, we pursue this possibility, but discover that the grammatical conditioning of copula absence in AAVE and creole varieties is distinct from the patterns found in second language learning data. We examine four sets of data on English acquired as a second language (Indian English, South African Indian English, Singaporean English, Spanish English) and show, using two statistical measures, that conditioning of copula absence in the second language data does not resemble the AAVE and creole pattern. (One possible exception is the high rates of omitted be with verbal predicates, for which we explore possible explanations.) We show further that typological diversity in copula systems also militates against a universal markedness-based pattern. The findings reduce the possibility that the overall AAVE/creole pattern derives from a general tendency in second language acquisition and increase the possibility that the pattern reflects a shared substrate influence from West African languages or other historical contact factors.
Challenges in contrast
Authors: Fetzer Anita
Published: April 2009

Challenges express the speaker’s intention not to comply with a proposition, force or presupposition communicated in and through a prior conversational contribution. This may be a directly adjacent contribution, some less directly adjacent contribution, or a conversational contribution uttered in some prior discourse. As for its sequential status, a challenge is a responsive contribution, and from an interpersonal perspective, it tends to carry a high degree of face-threatening potential. A felicitous analysis of a challenge thus needs to go beyond a single conversational contribution, not only accommodating context but also the nature of a challenge’s embeddedness in context. The contribution is organized as follows: The first section systematizes the necessary and sufficient contextual constraints and requirements for a conversational contribution to be assigned the status of a challenge. The second part argues for a challenge to be conceptualized as a particularized contextual configuration, which may serve as a tertium comparationis in contrastive pragmatics. The third section exemplifies the frame of reference with a contrastive analysis of British and German challenges adopted from a corpus of political interviews. In both sets of data, challenges tend to be realized implicitly, and in both sets, challenging the content of a contribution is more frequent than challenging its force or presuppositions. While the British data display a wider variety of challenges, the German data prefer the content-based, implicitly realized challenge.
Eating to exit: autophagy-enabled senescence revealed: Figure 1.
Authors: White Eileen , Lowe Scott W.
Published: April 2009

Autophagy and senescence are two distinct cellular responses to stress that are also tumor suppression mechanisms. In this issue of Genes & Development, Young and colleagues (pp. 798–803) discovered that autophagy is induced during and facilitates the process of senescence. Knowing now that these two pathways are functionally intertwined sets the stage for establishing how they function cooperatively in the cancer setting.
Two conserved regulatory cytoplasmic poly(A) polymerases, GLD-4 and GLD-2, regulate meiotic progression in C. elegans
Authors: Schmid Mark , Küchler Beate , Eckmann Christian R.
Published: April 2009

Translational regulation is heavily employed during developmental processes to control the timely accumulation of proteins independently of gene transcription. In particular, mRNA poly(A) tail metabolism in the cytoplasm is a key determinant for balancing an mRNA's translational output and its decay rate. Noncanonical poly(A) polymerases (PAPs), such as germline development defective-2 (GLD-2), can mediate poly(A) tail extension. Little is known about the regulation and functional complexity of cytoplasmic PAPs. Here we report the discovery of Caenorhabditis elegans GLD-4, a cytoplasmic PAP present in P granules that is orthologous to Trf4/5p from budding yeast. GLD-4 enzymatic activity is enhanced by its interaction with GLS-1, a protein associated with the RNA-binding protein GLD-3. GLD-4 is predominantly expressed in germ cells, and its activity is essential for early meiotic progression of male and female gametes in the absence of GLD-2. For commitment into female meiosis, both PAPs converge on at least one common target mRNA—i.e., gld-1 mRNA—and, as a consequence, counteract the repressive action of two PUF proteins and the putative deadenylase CCR-4. Together our findings suggest that two different cytoplasmic PAPs stabilize and translationally activate several meiotic mRNAs to provide a strong fail-safe mechanism for early meiotic progression.
KEEP foster‐parent training intervention: model description and effectiveness
Authors: Price Joseph M. , Chamberlain Patricia , Landsverk John , Reid John
Published: April 2009

In this paper, we describe the development and history of the Keeping Foster Parents Trained and Supported (KEEP) foster‐parent training intervention. KEEP intervention represents a modified version of the Multidimensional Treatment Foster Care intervention developed by interventionists at the Oregon Social Learning Center and is designed to provide training and support for children ages 5–11 in regular foster care. We also report on the initial findings from a programme of research focused on determining the effectiveness of the intervention. Thus far, the results indicate that the intervention is effective in reducing child behaviour problems and that the effects of the intervention are mediated through changes in parenting behaviour. There is also evidence that the KEEP foster‐parent training intervention increases the chances of a positive change of placement (e.g. child reunited with biological parents) and mitigates the negative risk‐enhancing effect of a history of multiple placements. We conclude with a discussion of unanswered questions and directions for future research.
Out of the Andes: patterns of diversification in clearwing butterflies
Authors: ELIAS M. , JORON M. , WILLMOTT K. , SILVA‐BRANDÃO K. L. , KAISER V. , ARIAS C. F. , PIÑEREZ L. M. GOMEZ , URIBE S. , BROWER A. V. Z. , FREITAS A. V. L. , JIGGINS C. D.
Published: April 2009

Global biodiversity peaks in the tropical forests of the Andes, a striking geological feature that has likely been instrumental in generating biodiversity by providing opportunities for both vicariant and ecological speciation. However, the role of these mountains in the diversification of insects, which dominate biodiversity, has been poorly explored using phylogenetic methods. Here we study the role of the Andes in the evolution of a diverse Neotropical insect group, the clearwing butterflies. We used dated species‐level phylogenies to investigate the time course of speciation and to infer ancestral elevation ranges for two diverse genera. We show that both genera likely originated at middle elevations in the Andes in the Middle Miocene, contrasting with most published results in vertebrates that point to a lowland origin. Although we detected a signature of vicariance caused by the uplift of the Andes at the Miocene–Pliocene boundary, most sister species were parapatric without any obvious vicariant barrier. Combined with an overall decelerating speciation rate, these results suggest an important role for ecological speciation and adaptive radiation, rather than simple vicariance.
The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging
Authors: Goetze O. , Treier R. , Fox M. , Steingoetter A. , Fried M. , Boesiger P. , Schwizer W.
Published: April 2009

Abstract  Conventional measurement of gastric secretion is invasive and cannot assess the intra‐gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T1 mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium‐DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double‐blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T1 mapping. Data was described by the κ‐coefficient (volume change after meal ingestion), by GE half time (T50) and maximal GE rate (GERmax) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [κ(GCV):1.6 ± 0.1 vs 0.6 ± 0.1; κ(TGV): 1.6 ± 0.1 vs 0.7 ± 0.1; P < 0.001]. T1 maps revealed a secretion layer above the meal, the volume of which was associated with κ (R2 = 83%, P < 0.001). TGV and GCV change were similar in both conditions (κ; P = ns). T50 was higher for pentagastrin than for placebo (84 ± 7 vs 56 ± 4min, P < 0.001); however, GERmax was similar (5.9 ± 0.6 vs 4.9 ± 0.4 mL min−1, P = ns). This study shows volume and distribution of gastric secretion can be quantified in‐vivo by non‐invasive MRI T1 mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T50; however, GE rate is unchanged.
Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patients
Authors: Leonardi A. , Sathe S. , Bortolotti M. , Beaton A. , Sack R.
Published: April 2009

Background:  To detect the presence of multiple mediators and growth factors in tears of vernal keratoconjunctivitis (VKC) patients with active disease using stationary phase antibody arrays.

Methods:  Tears were collected from 12 normal subjects (CT) and 24 active VKC patients. Tears were centrifuged and successively probed using three microwell plate arrays specific for: (i) cytokines: interleukin (IL)‐2, IL‐4, IL‐5, IL‐8, IL‐10, IL‐12, IL‐13, interferon‐γ and tumour necrosis factor‐α; (ii) growth factors: basic fibroblast growth factor (bFGF), platelet‐derived growth factor, thrombopoietin, angiopoietin‐2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), keratocyte growth factor, tissue inhibitor of metalloprotease (TIMP)‐1 and heparin‐binding epithelial growth factor (HB‐EGF) and (iii) matrix metalloprotease (MMP)‐1, MMP‐2, MMP‐3, MMP‐8, MMP‐9, MMP‐10, MMP‐13, TIMP‐1 and TIMP‐2.

Results:  Interleukin‐8 signals were detected in all CT and highly detected in all VKC samples. The Th2‐type cytokines, IL‐4, IL‐5 and IL‐10 were detected only in tears of VKC patients. Signals for bFGF, HB‐EGF, VEGF and HGF were detected in 41–87% of VKC samples and in few CT samples. Only TIMP‐1 and TIMP‐2 were found in all normal and patient tear samples, whereas MMP‐1, MMP‐2, MMP‐3, MMP‐9 and MMP‐10 were highly present in all VKC samples.

Conclusions:  Stationary phase antibody array methodology was useful for the screening of various cytokines, growth factors and MMPs in tears. These analyses identified in tears of VKC patients previously unreported factors including MMP‐3 and MMP‐10 and multiple proteases, growth factors and cytokines, which may all play an important role in the pathogenesis of conjunctival inflammation.
An exploratory study of the association between reactive attachment disorder and attachment narratives in early school‐age children
Authors: Minnis Helen , Green Jonathan , O’Connor Thomas G. , Liew Ashley , Glaser D. , Taylor E. , Follan M. , Young D. , Barnes J. , Gillberg C. , Pelosi A. , Arthur J. , Burston A. , Connolly B. , Sadiq F.A.
Published: April 2009

Objective:  To explore attachment narratives in children diagnosed with reactive attachment disorder (RAD).

Method:  We compared attachment narratives, as measured by the Manchester Child Attachment Story Task, in a group of 33 children with a diagnosis of RAD and 37 comparison children.

Results:  The relative risk (RR) for children with RAD having an insecure attachment pattern was 2.4 (1.4–4.2) but 30% were rated as securely attached. Within the RAD group, children with a clear history of maltreatment were more likely to be Insecure‐Disorganised than children without a clear history of maltreatment.

Conclusions:  Reactive attachment disorder is not the same as attachment insecurity, and questions remain about how attachment research informs clinical research on attachment disorders.
Use of Telemetered Electrograms in the Assessment of Normal Pacemaker Function
Authors: CLARKE MALCOLM , ALLEN ALBERT
Published: April 2009

The facility of direct real‐time endocardial electrogram recording offered by newer pacemaker models can be helpful in the assessment of normal pacemaker function. Confirmation of the main hallmarks of sensing (amplitude, slew rate, and timing of the electrogram) can be achieved. Assessment of pacing capture also can be made; techniques for further analysis using external signal averaging can enhance this. The measurement of atrial and ventricular electrograms by telemetry has led to alterations in the protocol used at implantation to allow for the input impedance of the sensing circuit of the pacemaker. Accurate measurements of retrograde VA conduction times and confirmation of normal upper rate limit behavior of ODD pacemakers can be achieved simply and reliably using telemetered electrograms from the permanent pacemaker system.
Teamwork Training for Interdisciplinary Applications
Authors: Foster Bev , Durham Carol , Sawning Susan , Frush Karen , Sherwood Gwen , Hobgood Cherri , Promes Susan , Woodyard Donald , Hollar David
Published: April 2009

Safe healthcare delivery in the emergency department is a team sport. Medical educators seek efficient and effective methods to teach and practice teamwork skills to all levels of interdisciplinary learners with the goal of enhancing communication, insuring smooth clinical operations, and improving patient safety. We present a new interdisciplinary, health professions teamwork curriculum, modified from TeamSTEPPS, that is efficient, effective, and can be delivered using multiple teaching modalities. This flexible curriculum structure begins with a brief didactic core designed to orient the learners to team concepts and invest them in the rationale for focusing on teamwork skills. This is followed by one of four additional instructional modalities: traditional didactic, interactive audience response didactic, low‐fidelity simulation (role play), and high‐fidelity patient simulation. Each of these additional modalities can be utilized singly or in combination to enhance the learners’ attitudes, knowledge, and skills in team‐based behaviors. Interdisciplinary cases have been defined, piloted, modified, and deployed at two major universities across more than 400 learners. Interdisciplinary simulation scenarios range from team‐based role play to high‐fidelity human patient simulation. Assessment cases using standardized patients are designed for interdisciplinary applications and focus on observable team‐based behaviors rather than clinical knowledge. All of these cases have accompanying assessment instruments for attitudes, knowledge, and skills. These instruments may be used for formative assessment to provide feedback to the learners and standardize the faculty's information delivery. If used in a summative manner they provide data for course completion criteria, remediation, or competency assessment.
Nephrogenic systemic fibrosis with a spectrum of clinical and histopathological presentation: a disorder of aberrant dermal remodeling
Authors: Deng A. , Martin D. Bilu , Spillane A. , Chwalek J. , Surin‐Lord S. , Brooks Sara , Petrali John , Sina B. , Gaspari A. , Kao G.
Published: April 2009

Background: Nephrogenic fibrosing dermopathy (NFD) has emerged as a clinicopathologic entity since 1997 and recently renamed as nephrogenic systemic fibrosis (NSF). The etiology and pathogenesis remain uncertain. Characteristic clinical presentation is described as diffuse thickening and hardening of the skin occurring in patients with renal insufficiency. Typical histological features include proliferation of CD34 positive fibrocytes, increased thick collagen bundles and mucin deposition, without significant inflammatory infiltrate. Variations in clinical presentations have been reported, including papular and plaque‐like skin lesions, focal lesion only, as well as systemic involvement. Histological changes can be subtle and non‐specific, overlapping with other disease processes and harboring features including calcification and osteoclast‐like giant cells with osseous metaplasia.

Methods: We reviewed patients with NSF that presented to our dermatology clinic by chart review, clinical examination and histological examination. Skin biopsy specimens were obtained from all cases. Histopathology evaluations were carried out by three dermatopathologists (AD, BS and GK) independently and the features were compared among all the cases. Special stains and immunohistochemistry study were also performed to highlight the histological features.

Results: Seven cases of NSF presented with a spectrum of clinical manifestations, from classic diffuse hardening of the skin to localized linear plaques. On histological examination, proliferation of CD34‐positive fibrocytes ranged from sparse to dense, collagen bundles ranged from thin to thick, and the interstitial dermal mucin accumulation ranged from scant‐patchy to abundant. In addition, the lesion displayed various degrees of vascular proliferation, inflammatory infiltrates and intensities of CD68 and Factor XIIIa staining. Two cases showed extensive dermal calcification and ossification.

Conclusion: NSF may present with a spectrum of clinical abnormalities, and exhibit overlapping histopathological features resembling cicatrix and other dermal reparative/regenerative processes. NSF may in fact to be a disorder of aberrant extracellular matrix remodeling in patients with renal insufficiency.

Deng A, Bilu Martin D, Spillane A, Chwalek J, St. Surin‐Lord S, Brooks S, Petrali J, Sina B, Gaspari A, Kao G. Nephrogenic systemic fibrosis with a spectrum of clinical and histopathological presentation: a disorder of aberrant dermal remodeling.
Global tests of regional effect on species richness of vascular plants and terrestrial vertebrates
Authors: Qian Hong
Published: April 2009

Determining the effects of regional and contemporary factors on large‐scale patterns in species richness has been a fundamental question in modern ecology and biogeography. However, few studies have examined effects of historical and regional factors on species richness at the global scale, and conclusions are often inconsistent or controversial. Here, I use a comprehensive dataset to examine regional effects on species richness of vascular plants and four taxa of terrestrial vertebrates (mammals, birds, reptiles, and amphibians) in the same set of sample units (ecoregions) in seven biogeographic realms across the globe. The same spatial scale and the same set of environmental variables, which are thought to influence large‐scale patterns in species richness of vascular plants and terrestrial vertebrates, are used for all the five taxa. Species richness of each taxon is compared across biogeographic realms. Regional effect on species richness has been found for all the five taxa. Of the 90 realm‐pair comparisons for the five taxa between observed richness of a region and the richness of the region predicted by the richness–environment relationship derived from the data of another region, 74 (82.2%) showed significant differences between observed and predicted species richness, indicating that a species richness–environment relationship developed for one region cannot accurately predict species richness in other regions of similar environments.
COMBINING GEOSTATISTICS AND MULTI‐ATTRIBUTE TRANSFORMS: A CHANNEL SAND CASE STUDY, BLACKFOOT OILFIELD (ALBERTA)
Authors: Russell B. , Hampson D. , Todorov T. , Lines L.
Published: April 2009

In this paper, we combine the methods of geostatistics and multi‐attribute reservoir parameter prediction (the multi‐attribute transform) for the integration of seismic and well log data, and illustrate this new procedure with a case study involving the prediction of porosity at the Blackfoot oilfield, central Alberta. The objectives of the survey were to delineate incised, valley‐fill sediments within the Early Cretaceous Glauconitic Formation at this field and to distinguish between sand‐fill and shale‐fill. The input consisted of twelve porosity logs together with a 3D seismic volume and the inversion of this volume. Although an excellent correlation was found between porosity and the initial inverted acoustic impedance volume, the combination of traditional geostatistics and the multi‐attribute transform produced an improved final result.

Our approach uses well logs to “train” the multi‐attribute transform algorithm. We first extract average porosity values over the depth zone of interest, and compare these values to average seismic attributes over the same zone. Cross‐validation is used to show which attributes are significant. We then apply the results of the training and cross‐validation to data slices derived from both the seismic data cube and the inverted cube to produce an initial porosity map. Finally, we improve the fit between the well‐log values and the porosity map using cokriging.
Art and Self
Authors: Hagman George
Published: April 2009

The following article presents a contemporary self‐psychological perspective on aesthetic experience, art, and creativity. The author argues that aesthetics is as important to human life as sex, hunger, aggression, love, and hate. Although we may rarely be conscious of it, aesthetic experience gives form, meaning, and, most importantly, value to everything we are, all we experience, and everything we do. Theoretically without it, life would be a shapeless, meaningless, and colorless series of sensations, events, and reactions. Aesthetic experience achieves its most refined form in the fine arts. However, we can also see its most archaic manifestation in the curve of the mother's shoulder during nursing, her heartbeat and breath, the melody of her voice, the balance of her eyes and smile—all embedded in the warmth, nourishment, and security of the mother–infant interaction. This article reviews recent analytic writings on psychoanalytic aesthetics that emphasize the central role of early childhood relational experiences in the emergence and structuralization of the sense of aesthetic form. The author argues that as a result of developmentally based processes of idealization, the child's aesthetic sense takes on a profound and lifelong concern with form and quality. The author extends this model and proposes a new definition of creativity and the nature of art. He argues that the creative artist is concerned not just with articulation of subjective states of feeling but also with the most refined and perfect expression possible of his or her internal vision. Although a major application of this model is to art and creativity, it is argued that aesthetic experience is a pervasive human trait that impacts on our entire experience of life, self, and relationships.
GRAVITATIONAL WAVES IN THE HYPERSPACE?
Authors: CORDA CHRISTIAN , FONTANA GIORGIO , CUADRADO GLORIA GARCIA
Published: April 2009

In the framework of the debate on high-frequency gravitational waves (GWs), after a review of GWs in standard General Relativity, which is due for completness, the possibility of merging such a traditional analysis with the hyperspace formalism that has been recently introduced in some papers in the literature, with the goal of a better understanding of manifolds dimensionality also in a cosmological framework, is discussed. Using the concept of refractive index in the hyperspace, spherical solutions are given and the propagation of GWs in a region of the hyperspace with a unitary refractive index is also discussed. Propagation phenomena associated to the higher dimensionality are proposed, possibly including nonlinear effects. Further and accurate studies in this direction are needed.
RENORMALIZATION SCHEME TO THE CHARGE TRANSFER EFFICIENCY OF SINGLE-STRAND DNA WITH LONG RANGE CORRELATED DISORDER
Authors: DENG CHAO-SHENG , XU HUI , WANG HUAN-YOU , LIU XIAO-LIANG
Published: April 2009

By using a renormalization group method together with a minimum set of parameters, the charge transfer efficiency of single-stranded synthetic guanine–cytosine DNA sequence with long-range correlated disorder is investigated. Numerical results for the transmission coefficient are derived and compared with those corresponding to periodic poly(GC) sequence. We find that, when the correlation exponent arrives at its critical value, new long-range correlations induced electronic states are formed within the energy gap between the guanine highest-occupied molecular orbital and cytosine lowest-unoccupied molecular orbital, and these two bands emerged into one at which transmission is ballistic. At the same time, a series of high-conductance peaks which indicate the existence of extended states appeared, revealing a presence of localization–delocalization phase transition in this gap. We also find that the transmission spectra are stable for all the correlation exponents which are greater than the critical one, and the above features are independent of the chain length of DNA sequence.
ON Π-NEAR-ARMENDARIZ RINGS
Authors: Ghalandarzadeh Sh. , Malakooti Rad P.
Published: April 2009

In this note we introduce a concept, so-called π-Near-Armendariz ring, that is a generalization of both Armendariz rings and 2-primal rings. We first observe the basic properties of π-Near-Armendariz rings, constructing typical examples. We next extend the class of π-Near-Armendariz rings, through various ring extensions.
Oral bovine lactoferrin improves bone status of ovariectomized mice
Authors: Blais Anne , Malet Arnaud , Mikogami Takashi , Martin-Rouas Christine , Tomé Daniel
Published: April 2009

The aim of the present study was to evaluate the effect of dietary lactoferrin on bone metabolism in vivo using a postmenopausal animal model. We investigated whether bovine lactoferrin (bLF) ingestion could prevent bone loss in ovariectomized mice. Twelve-week-old female C3H mice either ovariectomized or sham operated were fed for 27 wk with the control diet (AIN-93M with 140 g of total milk protein as a protein source per kg of diet). Four groups of ovariectomized mice received diets including different concentrations of bLF (1, 5, 10, or 20 g of total milk protein were replaced by bLF). Ovariectomy induced a decreased uterine weight and a smaller gain of bone mineral density. Immunoreactive bLF was detected in the peripheral blood, and its concentration was related to the amount of bLF ingestion. bLF supplementation to the diet improved bone mineral density (BMD) and femoral failure load in a dose-dependent manner. We confirmed the direct effects of bLF in vitro using established and primary cultures of murine bone cells. Addition of bLF to the culture medium at a concentration of between 1 and 1,000 μg/ml stimulated both cell growth and differentiation of osteoblastic MC3T3 cells while inhibiting the growth of preosteoclastic RAW 267.4 cells. In primary culture of mixed bone cells, an enhanced osteoblast differentiation was associated with an inhibition of osteoclast differentiation at lower bLF concentrations (1–10 μg/ml). In conclusion, these findings suggest that dietary lactoferrin supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption.
Tonic Activation of GABAB Receptors Reduces Release Probability at Inhibitory Connections in the Cerebellar Glomerulus
Authors: Mapelli Lisa , Rossi Paola , Nieus Thierry , D'Angelo Egidio
Published: April 2009

In the cerebellum, granule cells are inhibited by Golgi cells through GABAergic synapses generating complex responses involving both phasic neurotransmitter release and the establishment of ambient γ-aminobutyric acid (GABA) levels. Although at this synapse the mechanisms of postsynaptic integration have been clarified to a considerable extent, the mechanisms of neurotransmitter release remained largely unknown. Here we have investigated the quantal properties of release during repetitive neurotransmission, revealing that tonic GABAB receptor activation by ambient GABA regulates release probability. Blocking GABAB receptors with CGP55845 enhanced the first inhibitory postsynaptic current (IPSC) and short-term depression in a train while reducing trial-to-trial variability and failures. The changes caused by CGP55845 were similar to those caused by increasing extracellular Ca2+ concentration, in agreement with a presynaptic GABAB receptor modulation of release probability. However, the slow tail following IPSC peak demonstrated a remarkable temporal summation and was not modified by CGP55845 or extracellular Ca2+ increase. This result shows that tonic activation of presynaptic GABAB receptors by ambient GABA selectively regulates the onset of inhibition bearing potential consequences for the dynamic regulation of signal transmission through the mossy fiber–granule cell pathway of the cerebellum.
High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer
Authors: Holstege Henne , Joosse Simon A. , van Oostrom Conny Th. M. , Nederlof Petra M. , de Vries Annemieke , Jonkers Jos
Published: April 2009

Approximately half of all hereditary breast cancers are compromised in their DNA repair mechanisms due to loss of BRCA1 or BRCA2 function. Previous research has found a strong correlation between BRCA mutation and TP53 mutation. However, TP53 mutation status is often indirectly assessed by immunohistochemical staining of accumulated p53 protein. We sequenced TP53 exons 2 to 9 in 21 BRCA1-related breast cancers and 37 sporadic breast tumors. Strikingly, all BRCA1-related breast tumors contained TP53 mutations, whereas only half of these tumors stained positive for p53 accumulation. Positive p53 staining correlates with the presence of TP53 hotspot mutations in both BRCA1-related and sporadic breast tumors. However, whereas the majority of sporadic breast tumors that stained negative for p53 accumulation had wild-type TP53, the majority of BRCA1-associated breast tumors that stained negative for p53 accumulation had protein-truncating TP53 mutations (nonsense, frameshift, and splice mutations). Therefore, the strong selection for p53 loss in BRCA1-related tumors is achieved by an increase of protein-truncating TP53 mutations rather than hotspot mutations. Hence, immunohistochemical detection of TP53 mutation could lead to misdiagnosis in approximately half of all BRCA1-related tumors. The presence of deleterious TP53 mutations in most, if not all, BRCA1-related breast cancers suggests that p53 loss of function is essential for BRCA1-associated tumorigenesis. BRCA1-related tumors may therefore be treated not only with drugs that target BRCA1 deficiency [e.g., poly(ADP-ribose) polymerase inhibitors] but also with drugs that selectively target p53-deficient cells. This raises interesting possibilities for combination therapies against BRCA1-deficient breast cancers and BRCA1-like tumors with homologous recombination deficiency. [Cancer Res 2009;69(8):3625–33]
Credentialing a Preclinical Mouse Model of Alveolar Rhabdomyosarcoma
Authors: Nishijo Koichi , Chen Qing-Rong , Zhang Lei , McCleish Amanda T. , Rodriguez Andrea , Cho Min Jung , Prajapati Suresh I. , Gelfond Jonathan A.L. , Chisholm Gary B. , Michalek Joel E. , Aronow Bruce J. , Barr Frederic G. , Randall R. Lor , Ladanyi Marc , Qualman Stephen J. , Rubin Brian P. , LeGallo Robin D. , Wang Chiayeng , Khan Javed , Keller Charles
Published: April 2009

The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for the unresectable and metastatic disease is dismal and unchanged for nearly three decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e., activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report, we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We show that Pax3:Fkhr expression increases during late preneoplasia but tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole-genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared with other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS, as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 “druggable” kinases overexpressed across species. The data affirm the accuracy of this genetically engineered mouse model. [Cancer Res 2009;69(7):2902–11]
Twist1-Mediated Adriamycin-Induced Epithelial-Mesenchymal Transition Relates to Multidrug Resistance and Invasive Potential in Breast Cancer Cells
Authors: Li Qing-Quan , Xu Jing-Da , Wang Wen-Juan , Cao Xi-Xi , Chen Qi , Tang Feng , Chen Zhong-Qing , Liu Xiu-Ping , Xu Zu-De
Published: April 2009

Purpose: Besides its therapeutic effects, chemotherapeutic agents also enhance the malignancy of treated cancers in clinical situations. Recently, epithelial-mesenchymal transition (EMT) has attracted attention in studies of tumor progression. We aimed to test whether transient Adriamycin treatment induces EMT and apoptosis simultaneously in cancer cells, clarify why the same type of cells responds differentially (i.e., apoptosis, EMT) to Adriamycin treatment, and elucidate the role of Twist1, the master regulator of EMT, in this process.

Experimental Design: In unsynchronized MCF7 cells or cells synchronized at different phases, apoptosis, EMT, and concurrent events [multidrug resistance (MDR) and tumor invasion] after Adriamycin or/and Twist1 small interfering RNA treatment were examined in vitro and in vivo. The Adriamycin-induced Twist1 expression and the interaction of Twist1 with p53-Mdm2 were examined by immunoblotting and immunoprecipitation, respectively.

Results: We showed in vitro that Adriamycin induced EMT and apoptosis simultaneously in a cell cycle–dependent manner. Only the cells undergoing EMT displayed enhanced invasion and MDR. Twist1 depletion completely blocked the mesenchymal transformation, partially reversed MDR, and greatly abolished invasion induced by Adriamycin. Also, we confirmed in vivo that Twist1 RNA interference improved the efficacy of Adriamycin for breast cancers. Further, Twist1 reduction in Adriamycin-treated cells promoted p53-dependent p21 induction and disrupted the association of p53 with Mdm2.

Conclusions: Our studies show the diverse responses to Adriamycin treatment in cells at different phases, suggest an unrecognized role of EMT in regulating MDR and invasion, and show the efficacy of Twist1 RNA interference in Adriamycin-based chemotherapies for breast cancer.
Validation of a New Simple Scale to Measure Symptoms in Atrial Fibrillation
Authors: Dorian Paul , Guerra Peter G. , Kerr Charles R. , O’Donnell Suzan S. , Crystal Eugene , Gillis Anne M. , Mitchell L. Brent , Roy Denis , Skanes Allan C. , Rose M. Sarah , Wyse D. George
Published: April 2009

Background—

Atrial fibrillation (AF) is commonly associated with impaired quality of life. There is no simple validated scale to quantify the functional illness burden of AF. The Canadian Cardiovascular Society Severity in Atrial Fibrillation (CCS-SAF) scale is a bedside scale that ranges from class 0 to 4, from no effect on functional quality of life to a severe effect on life quality. This study was performed to validate the scale.

Methods and Results—

In 484 patients with documented AF (62.2�12.5 years of age, 67% men; 62% paroxysmal and 38% persistent/permanent), the SAF class was assessed and 2 validated quality-of-life questionnaires were administered: the SF-36 generic scale and the disease-specific AFSS (University of Toronto Atrial Fibrillation Severity Scale). There is a significant linear graded correlation between the SAF class and measures of symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF. Patients with SAF class 0 had age- and sex-standardized SF-36 scores of 0.15�0.16 and −0.04�0.31 (SD units), that is, units away from the mean population score for the mental and physical summary scores, respectively. For each unit increase in SAF class, there is a 0.36 and 0.40 SD unit decrease in the SF-36 score for the physical and mental components. As the SAF class increases from 0 to 4, the symptom severity score (range, 0 to 35) increases from 4.2�5.0 to 18.4�7.8 (
P
<0.0001).

Conclusions—

The CCS-SAF scale is a simple semiquantitative scale that closely approximates patient-reported subjective measures of quality of life in AF and may be practical for clinical use.
Adenosine Stress 64- and 256-Row Detector Computed Tomography Angiography and Perfusion Imaging
Authors: George Richard T. , Arbab-Zadeh Armin , Miller Julie M. , Kitagawa Kakuya , Chang Hyuk-Jae , Bluemke David A. , Becker Lewis , Yousuf Omair , Texter John , Lardo Albert C. , Lima João A.C.
Published: April 2009

Background—

Multidetector computed tomography coronary angiography (CTA) is a robust method for the noninvasive diagnosis of coronary artery disease. However, in its current form, CTA is limited in its prediction of myocardial ischemia. The purpose of this study was to test whether adenosine stress computed tomography myocardial perfusion imaging (CTP), when added to CTA, can predict perfusion abnormalities caused by obstructive atherosclerosis.

Methods and Results—

Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses ≥50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively.

Conclusions—

The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.
An Uighur Version of Vāgbhata's Astāngahrdayasamhitā
Authors: Maue Dieter
Published: April 2009

The Astāngahrdayasamhitā (AHS), one of the most important works on Old Indian medicine (āyurveda), is unattested in Central Asia. Several fragments of the Berlin Turfan collection, however, can be attributed to an Uighur translation. They are edited, translated, commented on and provided with glossaries. Special attention is paid to the translation technique.
Resonant Wave Interactions in the Presence of a Diurnally Varying Heat Source
Authors: Raupp Carlos F. M. , Silva Dias Pedro L.
Published: April 2009

Resonant interactions among equatorial waves in the presence of a diurnally varying heat source are studied in the context of the diabatic version of the equatorial β-plane primitive equations for a motionless, hydrostatic, horizontally homogeneous and stably stratified background atmosphere. The heat source is assumed to be periodic in time and of small amplitude [i.e., O(ɛ)] and is prescribed to roughly represent the typical heating associated with deep convection in the tropical atmosphere. In this context, using the asymptotic method of multiple time scales, the free linear Rossby, Kelvin, mixed Rossby–gravity, and inertio-gravity waves, as well as their vertical structures, are obtained as leading-order solutions. These waves are shown to interact resonantly in a triad configuration at the O(ɛ) approximation, and the dynamics of these interactions have been studied in the presence of the forcing.

It is shown that for the planetary-scale wave resonant triads composed of two first baroclinic equatorially trapped waves and one barotropic Rossby mode, the spectrum of the thermal forcing is such that only one of the triad components is resonant with the heat source. As a result, to illustrate the role of the diurnal forcing in these interactions in a simplified fashion, two kinds of triads have been analyzed. The first one refers to triads composed of a k = 0 first baroclinic geostrophic mode, which is resonant with the stationary component of the diurnal heat source, and two dispersive modes, namely, a mixed Rossby–gravity wave and a barotropic Rossby mode. The other class corresponds to triads composed of two first baroclinic inertio-gravity waves in which the highest-frequency wave resonates with a transient harmonic of the forcing. The integration of the asymptotic reduced equations for these selected resonant triads shows that the stationary component of the diurnal heat source acts as an “accelerator” for the energy exchanges between the two dispersive waves through the excitation of the catalyst geostrophic mode. On the other hand, since in the second class of triads the mode that resonates with the forcing is the most energetically active member because of the energy constraints imposed by the triad dynamics, the results show that the convective forcing in this case is responsible for a longer time scale modulation in the resonant interactions, generating a period doubling in the energy exchanges. The results suggest that the diurnal variation of tropical convection might play an important role in generating low-frequency fluctuations in the atmospheric circulation through resonant nonlinear interactions.
The Contribution of Mesoscale Convective Complexes to Rainfall across Subtropical South America
Authors: Durkee Joshua D. , Mote Thomas L. , Shepherd J. Marshall
Published: April 2009

This study uses a database consisting of 330 austral warm-season (October–May) mesoscale convective complexes (MCCs) during 1998–2007 to determine the contribution of MCCs to rainfall across subtropical South America (SSA). A unique precipitation analysis is conducted using Tropical Rainfall Measuring Mission (TRMM) 3B42 version 6 data. The average MCC produces 15.7 mm of rainfall across 381 000 km2, with a volume of 7.0 km3. MCCs in SSA have the largest precipitation areas compared to North American and African systems. MCCs accounted for 15%–21% of the total rainfall across portions of northern Argentina and Paraguay during 1998–2007. However, MCCs account for larger fractions of the total precipitation when analyzed on monthly and warm-season time scales. Widespread MCC rainfall contributions of 11%–20% were observed in all months. MCCs accounted for 20%–30% of the total rainfall between November and February, and 30%–50% in December, primarily across northern Argentina and Paraguay. MCCs also produced 25%–66% of the total rainfall across portions of west-central Argentina. Similar MCC rainfall contributions were observed during warm seasons. An MCC impact factor (MIF) was developed to determine the overall impact of MCC rainfall on warm-season precipitation anomalies. Results show that the greatest impacts on precipitation anomalies from MCC rainfall were located near the center of the La Plata basin. This study demonstrates that MCCs in SSA produce widespread precipitation that contributes substantially to the total rainfall across the region.