bluuebunny/crossref_metadata_2025 huggingface dataset:
“Illicit Traffic in Cultural Objects: Law Ethics and the Realities”: Workshop Co-organized by the Institute of Advanced Studies and the Law School of the University of Western Australia, Perth, 4–5 August 2011
Authors: Prott Lyndel
Published: February 2012

Particularly in the 1980s and 1990s, universities and nongovernmental organizations, as well as UNESCO, have held innumerable meetings, workshops, and conferences on the subject of illicit traffic by. The “Illicit Traffic in Cultural Objects: Law Ethics and the Realities” workshop, however, is distinguished by two important elements. First, it emphasizes the importance of the issue for Asian and Pacific countries. Although there have been some meetings focused on the region of Asia—such as the meeting in Polonnaruwa, Sri Lanka, in 2003; one in Bangkok in 2004; and one specifically including oceanic countries in Brisbane in 1996—these are few compared to meetings held on illicit traffic in Europe and North America. The second aspect is the range of expertise of the participants. Though we are used to seeing dealers, archaeologists, and lawyers debate the subject, this workshop included on-the-ground managers, an expert in systems of detection, as well as specialists in particular fields such as underwater heritage, postconflict restoration. and criminology.
Congenital heart defects in La Réunion Island: a 6-year survey within a EUROCAT-affiliated congenital anomalies registry
Authors: Bourdial Hélène , Jamal-Bey Karim , Edmar Abdelhafid , Caillet Dominique , Wuillai Françoise , Bernede-Bauduin Claire , Boumahni Brahim , Robillard Pierre-Yves , Kauffmann Edouard , Laffitte Annick , Touret Yasmina , Cuillier Fabrice , Fourmaintraux Alain , Alessandri Jean-Luc , Gérardin Patrick , Randrianaivo Hanitra
Published: February 2012

Objectives

This study compares the prevalence and perinatal mortality of congenital heart defects on La Réunion with European (EUROCAT) standards.

Methods and results

Data were extracted from a EUROCAT-affiliated congenital malformations registry, covering 88,025 births during the period 2002–2007, on the whole island territory. A total of 512 congenital heart defects were registered, including 424 live births, 18 foetal deaths from 16 weeks of gestation, and 70 terminations of pregnancy. The total prevalence of congenital heart defects was 5.8 per 1000 births and live birth prevalence was 4.8 per 1000. The total prevalence of non-chromosomal congenital heart defects was 5.1 per 1000 births, of which 3% were perinatal deaths, 33.3% prenatally diagnosed, and 11.6% termination of pregnancy. Severe non-chromosomal congenital heart defects – excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis – occurred in 2.1 per 1000 births, of which 10.3% were perinatal deaths, 59.1% prenatally diagnosed, and 24.3% termination of pregnancy. Of the severe congenital heart defects, the rates of single ventricle (0.20‰), Ebstein anomaly (0.11‰), common arterial trunk (0.25‰), and atrioventricular septal defect (0.62‰) exceeded averages found in Europe, although coarctation of the aorta was infrequent. Conversely, rates of ventricular septal defects, atrial septal defects, and pulmonary valve stenosis were inferior to European standards. Slightly less than half of the congenital heart defects of chromosomal origin were associated with Down syndrome.

Conclusion

In La Réunion, the total prevalence of congenital heart defects is far inferior to that found in Europe. The difference can be attributable to lower prevalences of mild congenital heart defects.
Intracoronary bone marrow cell application for terminal heart failure in children
Authors: Rupp Stefan , Jux Christian , Bönig Halvard , Bauer Jürgen , Tonn Torsten , Seifried Erhard , Dimmeler Stefanie , Zeiher Andreas M. , Schranz Dietmar
Published: February 2012

Introduction

In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports.

Method and results

Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction.

Conclusion

Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.
Composing for a Networked, Pulse-Based, Laptop Orchestra
Authors: Ogborn David
Published: February 2012

Guided by the idea of participatory culture, networked pulse synchronisation and live coding have been core approaches in the activity of the Cybernetic Orchestra, an electronic performance ensemble at McMaster University in Hamilton, Canada. Following general discussion of the way in which networked pulse-based music and live coding work within this orchestra, there is specific discussion of a number of compositional models and practices that have been found effective, including code-sharing, instruction-scores, code as material, and physical performance.
DISCRETE CHOICE AND COMPLEX DYNAMICS IN DETERMINISTIC OPTIMIZATION PROBLEMS
Authors: Kamihigashi Takashi
Published: February 2012

This paper shows that complex dynamics arises naturally in deterministic discrete choice problems. In particular, it shows that if the objective function of a maximization problem can be written as a function of a sequence of discrete variables, and if the (maximized) value function is strictly increasing in an exogenous variable, then for almost all values of the exogenous variable, any optimal path exhibits aperiodic dynamics. This result is applied to a maximization problem with indivisible durable goods, as well as to a Ramsey model with an indivisible consumption good. In each model, it is shown that optimal dynamics is almost always complex. These results are illustrated with various numerical examples.
Meeting the family: Measuring effectiveness of family meetings in a specialist inpatient palliative care unit
Authors: Hannon Breffni , O'Reilly Valerie , Bennett Kathleen , Breen Karen , Lawlor Peter G.
Published: February 2012

Objective:

The World Health Organization (WHO) definition of palliative care as “an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness …” recognizes the importance of family members in this setting. In practice, family meetings account for a significant amount of the weekly workload in a specialist inpatient palliative care unit. Despite this, there is little empirical evidence to support the benefits of family meetings from the perspective of family members.

Method:

A prospective study over 6 months, invited a designated family member to complete a self-report instrument (SRI) and the Family Inventory of Needs (FIN) questionnaire prior to, immediately following, and 48 hours after a planned family meeting attended by several members of the multidisciplinary team.

Results:

Thirty-one designated family members completed the study. The SRIs completed prior to a family meeting identified particular areas of concern and worry for family members, and also helped to generate an agenda based on the family's particular needs. The pre-meeting FIN identified areas of patient care of greatest importance to each family member, and asked them to rate whether particular care needs were presently met or unmet, in their opinion, by the healthcare team caring for the patient. Following the family meeting, repeat SRIs showed an overall reduction in concerns and increased confidence in dealing with those issues raised. Post-family meeting FIN scores confirmed a greater number of met care needs compared with pre-meeting scores, all of which were sustained over time.

Significance of results:

This study confirms the value of planned multidisciplinary family meetings for patients in specialist inpatient palliative care units. It identifies the often unmet needs of family members and the sustained benefits associated with formal family meetings.
A PROBABILISTIC SEMANTICS FOR COUNTERFACTUALS. PART B
Authors: LEITGEB HANNES
Published: February 2012

This is part B of a paper in which we defend a semantics for counterfactuals which is probabilistic in the sense that the truth condition for counterfactuals refers to a probability measure. Because of its probabilistic nature, it allows a counterfactual ‘ifAthenB’ to be true even in the presence of relevant ‘Aand notB’-worlds, as long such exceptions are not too widely spread. The semantics is made precise and studied in different versions which are related to each other by representation theorems. Despite its probabilistic nature, we show that the semantics and the resulting system of logic may be regarded as a naturalistically vindicated variant of David Lewis’ truth-conditional semantics and logic of counterfactuals. At the same time, the semantics overlaps in various ways with the non-truth-conditional suppositional theory for conditionals that derives from Ernest Adams’ work. We argue that counterfactuals have two kinds of pragmatic meanings and come attached with two types of degrees of acceptability or belief, one being suppositional, the other one being truth based as determined by our probabilistic semantics; these degrees could not always coincide due to a new triviality result for counterfactuals, and they should not be identified in the light of their different interpretation and pragmatic purpose. However, for plain assertability the difference between them does not matter. Hence, if the suppositional theory of counterfactuals is formulated with sufficient care, our truth-conditional theory of counterfactuals is consistent with it. The results of our investigation are used to assess a claim considered by Hawthorne and Hájek, that is, the thesis that most ordinary counterfactuals are false.
IDENTITY AND DISCERNIBILITY IN PHILOSOPHY AND LOGIC
Authors: LADYMAN JAMES , LINNEBO ØYSTEIN , PETTIGREW RICHARD
Published: February 2012

Questions about the relation between identity and discernibility are important both in philosophy and in model theory. We show how a philosophical question about identity and discernibility can be ‘factorized’ into a philosophical question about the adequacy of a formal language to the description of the world, and a mathematical question about discernibility in this language. We provide formal definitions of various notions of discernibility and offer a complete classification of their logical relations. Some new and surprising facts are proved; for instance, that weak discernibility corresponds to discernibility in a language with constants for every object, and that weak discernibility is the most discerning nontrivial discernibility relation.
The retrievals and analysis of clear‐sky water vapor density in the Arctic regions from MWHS measurements on FY‐3A satellite
Authors: He Jieying , Zhang Shengwei , Wang Zhenzhan
Published: February 2012

The atmospheric humidity profiles of clear sky in the Arctic regions were retrieved from the microwave humidity sounder on China's FY‐3A satellite using the back‐propagation neural network algorithm. The algorithm was developed using the reliable measurements of surface temperature, humidity, and pressure as well as atmospheric temperature and humidity profiles from radiosonde observations. Considering the influence of sounding geometry, different surface types, and atmospheric conditions, we improved the commonly used back‐propagation artificial neural network by treating the Mexican hat wavelet function as a transfer function and transforming the input data space. The retrieved root‐mean‐square (RMS) error is about 0.12 g/m3 in absolute humidity (water vapor density) profiles and 12.7% in relative humidity profiles. Water vapor density retrievals in winter are in acceptable agreement with profiles from radiosonde, but the agreement of the summer data was not as good. Furthermore, the retrieval model has been used in another Arctic station with a mean water vapor density RMS error of 0.185 g/m3 and 18.3% for a relative humidity profile for all seasons in 2008 at 12:00 UT.
Microstructure measurements along a quasi‐meridional transect in the northeastern Atlantic Ocean
Authors: Jurado E. , van der Woerd H. J. , Dijkstra H. A.
Published: February 2012

This study presents vertical profiles of turbulence parameters obtained in the upper 100 m of the northeastern Atlantic Ocean along a transect from tropical permanently stratified waters to subpolar seasonally stratified waters in July–August 2009. The focus is to fully characterize the vertical mixing along this transect for further studies related to phytoplankton and nutrient distributions. Derived values of temperature eddy diffusivity KT, of temperature variance dissipation rate χT, and of turbulent kinetic energy dissipation rate ε indicate a northward increase of turbulent mixing below the mixed layer. In the northern stations where the wind stress is sufficiently high, the vertical distributions of ε in the mixed layer follow the wind stress scaling. The related low wind‐scaling factors, and the low values of ε encountered at this cruise, are in agreement with a strongly stratified upper water column at midday in summer.
Stochastic analysis of tsunami runup due to heterogeneous coseismic slip and dispersion
Authors: Løvholt F. , Pedersen G. , Bazin S. , Kühn D. , Bredesen R. E. , Harbitz C.
Published: February 2012

Most tsunami models apply dislocation models that assume uniform slip over the entire fault plane, followed by standard analytical models based on Volterra's theory of elastic dislocations for the seabed deformation. In contrast, we quantify tsunami runup variability for an earthquake with fixed magnitude but with heterogeneous rupture distribution assuming plane wave propagation (i.e., an infinitely long rupture). A simple stochastic analysis of 500 slip realizations illustrates the expected variability in coseismic slip along a fault plane and the subsequent runup that occurs along a coastline in the near field. Because of the need for systematically analyzing different fault geometries, grid resolutions, and hydrodynamic models, several hundred thousand model runs are required. Thus, simple but efficient linear models for the tsunami generation, propagation, and runup estimation are used. The mean value and variability of the maximum runup is identified for a given coastal slope configuration and is analyzed for different dip angles. On the basis of the ensemble runs, nonhydrostatic effects are discussed with respect to their impact on generation, nearshore propagation, and runup. We conclude that for the geometry and magnitude investigated, nonhydrostatic effects reduce the variability of the runup; that is, hydrostatic models will produce an artificially high variability.
MISR observations of Etna volcanic plumes
Authors: Scollo S. , Kahn R. A. , Nelson D. L. , Coltelli M. , Diner D. J. , Garay M. J. , Realmuto V. J.
Published: February 2012

In the last twelve years, Mt. Etna, located in eastern Sicily, has produced a great number of explosive eruptions. Volcanic plumes have risen to several km above sea level and created problems for aviation and the communities living near the volcano. A reduction of hazards may be accomplished using remote sensing techniques to evaluate important features of volcanic plumes. Since 2000, the Multiangle Imaging SpectroRadiometer (MISR) on board NASA's Terra spacecraft has been extensively used to study aerosol dispersal and to extract the three‐dimensional structure of plumes coming from anthropogenic or natural sources, including volcanoes. In the present work, MISR data from several explosive events occurring at Etna are analyzed using a program named MINX (MISR INteractive eXplorer). MINX uses stereo matching techniques to evaluate the height of the volcanic aerosol with a precision of a few hundred meters, and extracts aerosol properties from the MISR Standard products. We analyzed twenty volcanic plumes produced during the 2000, 2001, 2002–03, 2006 and 2008 Etna eruptions, finding that volcanic aerosol dispersal and column height obtained by this analysis is in good agreement with ground‐based observations. MISR aerosol type retrievals: (1) clearly distinguish volcanic plumes that are sulphate and/or water vapor dominated from ash‐dominated ones; (2) detect even low concentrations of volcanic ash in the atmosphere; (3) demonstrate that sulphate and/or water vapor dominated plumes consist of smaller‐sized particles compared to ash plumes. This work highlights the potential of MISR to detect important volcanic plume characteristics that can be used to constrain the eruption source parameters in volcanic ash dispersion models. Further, the possibility of discriminating sulphate and/or water vapor dominated plumes from ash‐dominated ones is important to better understand the atmospheric impact of these plumes.
Effect of aerosol size distribution changes on AOD, CCN and cloud droplet concentration: Case studies from Erfurt and Melpitz, Germany
Authors: Romakkaniemi S. , Arola A. , Kokkola H. , Birmili W. , Tuch T. , Kerminen V.‐M. , Räisänen P. , Smith J. N. , Korhonen H. , Laaksonen A.
Published: February 2012

For the period of 1990 to 2000, atmospheric particulate mass concentrations have decreased in Central Europe. Simultaneously, the amount of shortwave radiation reaching the ground increased during clear sky conditions. The aerosol indirect effect has not been seen as clearly, as the radiation reaching the ground during overcast conditions has not increased as much as might be expected. Here we show that this may be caused by the condensation kinetics of water during cloud droplet formation. The decrease in the particulate mass led to a clear decrease in the number concentration of cloud condensation nuclei (CCN). However, in urban areas a relatively larger decrease in the number of particles in the upper end of the accumulation mode has led to slower condensation of water. As a result, a higher maximum supersaturation is reached during the cloud droplet formation. This compensates for the effect of decreased CCN concentrations. For example in Erfurt between 1991 and 1996, the aerosol properties changed so that aerosol optical depth decreased by 58% and CCN concentration decreased by 25 to 50%. These led to a 4 to 12% reduction in cloud droplet number concentration (CDNC) and less than a 2 Wm−2 increase in shortwave radiation during overcast conditions. These results demonstrate that locally the aerosol direct effect can be much larger than the aerosol indirect effect. Furthermore, even though AOD appears to be a valid proxy for CCN, the correlation between AOD and CDNC is not straightforward and thus AOD cannot be used as a proxy for CDNC.
Grooms receives 2011 Donald L. Turcotte Award
Authors: Anonymous
Published: February 2012

Ian Grooms has been awarded the AGU Donald L. Turcotte Award, given annually to recent Ph.D. recipients for outstanding dissertation research that contributes directly to the field of nonlinear geophysics. Grooms's thesis is entitled “Asymptotic and numerical methods for rapidly rotating buoyant flow.” He presented an invited talk and was formally presented with the award at the 2011 AGU Fall Meeting, held 5–9 December in San Francisco, Calif. Grooms received his B.S. in mathematics from the College of William and Mary, Williamsburg, Va., in 2005. He received a Ph.D. in applied mathematics in 2011 under the supervision of Keith Julien at the University of Colorado at Boulder. His research interests include asymptotic and numerical methods for multiscale problems in geophysical fluid dynamics.
Pulling regional weather from the climate record
Authors: Schultz Colin
Published: February 2012

At its core, weather is fueled by the redistribution of energy, and the medium for this regional shuffling is the surface atmosphere. Adjacent air masses are characterized by different physical properties, with atmospheric fronts demarcating the boundaries between them. A passing front can bring storms and heat waves, or, expressed more mundanely, sudden changes in atmospheric conditions: temperature, humidity, and pressure. Despite the power of atmospheric fronts in explaining regional weather, little effort has been put into understanding front frequency or dynamics from a climatic perspective.
Nanofluid based optical sensor for rapid visual inspection of defects in ferromagnetic materials
Authors: Mahendran V. , Philip John
Published: February 2012

We have developed a simple sensor for imaging internal defects in materials using a magnetically polarizable nanoemulsion. The gradient in the magnetic flux lines around the defective region leads to the formation of one-dimensional nanodroplet arrays along the field direction, which incredibly diffract the incident white light to produce bright colors. As the diffracted wavelength has a direct correlation with the defect features, this approach enable visual inspection of ferromagnetic components and has several advantages over existing flux leakage sensors in terms of cost, re-usability and complexity.
Plumatella trasimenica and Plumatella timwoodi, two new species belonging to the 'repens group' from central Italy (Bryozoa : Phylactolaemata : Plumatellidae)
Authors: Taticchi Maria Illuminata , Elia Antonia Concetta , Todini Chiara , Prearo Marino
Published: February 2012

Two new species – Plumatella trasimenica, from Lake Trasimeno and from an external sedimentation pond of a tropical fish farm, and Plumatella timwoodi, from Lake Piediluco – are described. These species belong to the ‘repens group’ (P. bushnelli Wood, 2001; P. geimermassardi Wood & Okamura, 2004; P. nitens Wood, 1996; P. repens (Linné, 1758); P. rugosa Wood, Geimer & Massard, 1998; P. similirepens Wood, 2001; P. viganoi Taticchi, 2010), because the annulus-chamber pores of the floatoblast are always characterised by the presence of long spines regularly distributed around the pores. Here, further morphological features, which distinguish them from the other species of the repens group, are described for both new species. The coexistence in the same sampling sites of species of the repens-group indicates that the new species are not ecomorphs of similar species.
Inhibitory effect of dietary lipids on chaperone-mediated autophagy
Authors: Rodriguez-Navarro Jose Antonio , Kaushik Susmita , Koga Hiroshi , Dall'Armi Claudia , Shui Guanghou , Wenk Markus R. , Di Paolo Gilbert , Cuervo Ana Maria
Published: February 2012

Cytosolic proteins can be selectively delivered to lysosomes for degradation through a type of autophagy known as chaperone-mediated autophagy (CMA). CMA contributes to intracellular quality control and to the cellular response to stress. Compromised CMA has been described in aging and in different age-related disorders. CMA substrates cross the lysosomal membrane through a translocation complex; consequently, changes in the properties of the lysosomal membrane should have a marked impact on CMA activity. In this work, we have analyzed the impact that dietary intake of lipids has on CMA activity. We have found that chronic exposure to a high-fat diet or acute exposure to a cholesterol-enriched diet both have an inhibitory effect on CMA. Lysosomes from livers of lipid-challenged mice had a marked decrease in the levels of the CMA receptor, the lysosome-associated membrane protein type 2A, because of loss of its stability at the lysosomal membrane. This accelerated degradation of lysosome-associated membrane protein type 2A, also described as the mechanism that determines the decline in CMA activity with age, results from its increased mobilization to specific lipid regions at the lysosomal membrane. Comparative lipidomic analyses revealed qualitative and quantitative changes in the lipid composition of the lysosomal membrane of the lipid-challenged animals that resemble those observed with age. Our findings identify a previously unknown negative impact of high dietary lipid intake on CMA and underscore the importance of diet composition on CMA malfunction in aging.
Nucleotide excision repair (NER) machinery recruitment by the transcription-repair coupling factor involves unmasking of a conserved intramolecular interface
Authors: Deaconescu Alexandra M. , Sevostyanova Anastasia , Artsimovitch Irina , Grigorieff Nikolaus
Published: February 2012

Transcription-coupled DNA repair targets DNA lesions that block progression of elongating RNA polymerases. In bacteria, the transcription-repair coupling factor (TRCF; also known as Mfd) SF2 ATPase recognizes RNA polymerase stalled at a site of DNA damage, removes the enzyme from the DNA, and recruits the Uvr(A)BC nucleotide excision repair machinery via UvrA binding. Previous studies of TRCF revealed a molecular architecture incompatible with UvrA binding, leaving its recruitment mechanism unclear. Here, we examine the UvrA recognition determinants of TRCF using X-ray crystallography of a core TRCF–UvrA complex and probe the conformational flexibility of TRCF in the absence and presence of nucleotides using small-angle X-ray scattering. We demonstrate that the C-terminal domain of TRCF is inhibitory for UvrA binding, but not RNA polymerase release, and show that nucleotide binding induces concerted multidomain motions. Our studies suggest that autoinhibition of UvrA binding in TRCF may be relieved only upon engaging the DNA damage.
Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels
Authors: Batra Nidhi , Burra Sirisha , Siller-Jackson Arlene J. , Gu Sumin , Xia Xuechun , Weber Gregory F. , DeSimone Douglas , Bonewald Lynda F. , Lafer Eileen M. , Sprague Eugene , Schwartz Martin A. , Jiang Jean X.
Published: February 2012

The connexin 43 (Cx43) hemichannel (HC) in the mechanosensory osteocytes is a major portal for the release of factors responsible for the anabolic effects of mechanical loading on bone formation and remodeling. However, little is known about how the Cx43 molecule responds to mechanical stimulation leading to the opening of the HC. Here, we demonstrate that integrin α5β1 interacts directly with Cx43 and that this interaction is required for mechanical stimulation-induced opening of the Cx43 HC. Direct mechanical perturbation via magnetic beads or conformational activation of integrin α5β1 leads to the opening of the Cx43 HC, and this role of the integrin is independent of its association with an extracellular fibronectin substrate. PI3K signaling is responsible for the shear stress-induced conformational activation of integrin α5β1 leading to the opening of the HC. These results identify an unconventional function of integrin that acts as a mechanical tether to induce opening of the HC and provide a mechanism connecting the effect of mechanical forces directly to anabolic function of the bone.
Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase
Authors: Mastrangelo Lina , Kim Ji-Eun , Miyanohara Atsushi , Kang Tae Hyuk , Friedmann Theodore
Published: February 2012

Lesch–Nyhan disease (LND) is an X-linked genetic disorder caused by mutations of the hypoxanthine guanine phosphoribosyltransferase (HPRT) purine biosynthesis gene and characterized by aberrant purine metabolism, deficient basal ganglia dopamine levels, dystonia, and severe neurobehavioral manifestations, including compulsive self-injurious behavior. Although available evidence has identified important roles for purinergic signaling in brain development, the mechanisms linking HPRT deficiency, purinergic pathways, and neural dysfunction of LND are poorly understood. In these studies aimed at characterizing purinergic signaling in HPRT deficiency, we used a lentivirus vector stably expressing an shRNA targeted to theHPRTgene to produce HPRT-deficient human CVB induced pluripotent stem cells and human HUES11 embryonic stem cells. Both CVB and HUES11 cells show >99% HPRT knockdown and demonstrate markedly decreased expression of the purinergic P2Y1 receptor mRNA. In CVB cells, P2Y1 mRNA and protein down-regulation by HPRT knockdown is refractory to activation by the P2Y1 receptor agonist ATP and shows aberrant purinergic signaling, as reflected by marked deficiency of the transcription factor pCREB and constitutive activation of the MAP kinases phospho-ERK1/2. Moreover, HPRT-knockdown CVB cells also demonstrate marked reduction of phosphorylated β-catenin. These results indicate that the housekeeping geneHPRTregulates purinergic signaling in pluripotent human stem cells, and that this regulation occurs at least partly through aberrant P2Y1-mediated expression and signaling. We propose that such mechanisms may play a role in the neuropathology of HPRT-deficiency LND and may point to potential molecular targets for modulation of this intractable neurological phenotype.
Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors
Authors: den Boon Femke S. , Chameau Pascal , Schaafsma-Zhao Qiluan , van Aken Willem , Bari Monica , Oddi Sergio , Kruse Chris G. , Maccarrone Mauro , Wadman Wytse J. , Werkman Taco R.
Published: February 2012

The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB
2
Rs) in the CNS. Here, we show that CB
2
Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP
3
R-dependent opening of Ca
2+
-activated Cl
−
channels. To investigate the functional role of CB
2
R activation, we induced neuronal firing and observed a CB
2
R-mediated reduction in firing frequency. The description of this unique CB
2
R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.
Solute carrier family 3 member 2 (Slc3a2) controls yolk syncytial layer (YSL) formation by regulating microtubule networks in the zebrafish embryo
Authors: Takesono Aya , Moger Julian , Farooq Sumera , Cartwright Emma , Dawid Igor B. , Wilson Stephen W. , Kudoh Tetsuhiro
Published: February 2012

The yolk syncytial layer (YSL) in the zebrafish embryo is a multinucleated syncytium essential for embryo development, but the molecular mechanisms underlying YSL formation remain largely unknown. Here we show that zebrafish solute carrier family 3 member 2 (Slc3a2) is expressed specifically in the YSL and that
slc3a2
knockdown causes severe YSL defects including clustering of the yolk syncytial nuclei and enhanced cell fusion, accompanied by disruption of microtubule networks. Expression of a constitutively active RhoA mimics the YSL phenotypes caused by
slc3a2
knockdown, whereas attenuation of RhoA or ROCK activity rescues the
slc3a2
-knockdown phenotypes. Furthermore,
slc3a2
knockdown significantly reduces tyrosine phosphorylation of c-Src, and overexpression of a constitutively active Src restores the
slc3a2
-knockdown phenotypes. Our data demonstrate a signaling pathway regulating YSL formation in which Slc3a2 inhibits the RhoA/ROCK pathway via phosphorylation of c-Src to modulate YSL microtubule dynamics. This work illuminates processes at a very early stage of zebrafish embryogenesis and more generally informs the mechanism of cell dynamics during syncytium formation.
Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice
Authors: Sun Hongmin , Xu Yuanxi , Sitkiewicz Izabela , Ma Yibao , Wang Xixi , Yestrepsky Bryan D. , Huang Yuping , Lapadatescu Martian C. , Larsen Martha J. , Larsen Scott D. , Musser James M. , Ginsburg David
Published: February 2012

The widespread occurrence of antibiotic resistance among human pathogens is a major public health problem. Conventional antibiotics typically target bacterial killing or growth inhibition, resulting in strong selection for the development of antibiotic resistance. Alternative therapeutic approaches targeting microbial pathogenicity without inhibiting growth might minimize selection for resistant organisms. Compounds inhibiting gene expression of streptokinase (SK), a critical group A streptococcal (GAS) virulence factor, were identified through a high-throughput, growth-based screen on a library of 55,000 small molecules. The lead compound [Center for Chemical Genomics 2979 (CCG-2979)] and an analog (CCG-102487) were confirmed to also inhibit the production of active SK protein. Microarray analysis of GAS grown in the presence of CCG-102487 showed down-regulation of a number of important virulence factors in addition to SK, suggesting disruption of a general virulence gene regulatory network. CCG-2979 and CCG-102487 both enhanced granulocyte phagocytosis and killing of GAS in an in vitro assay, and CCG-2979 also protected mice from GAS-induced mortality in vivo. These data suggest that the class of compounds represented by CCG-2979 may be of therapeutic value for the treatment of GAS and potentially other Gram-positive infections in humans.
Scalar semantics in the foreground
Authors: Hillert Albin
Published: February 2012

This paper offers a corpus-based study of the noun phrase pattern exemplified in This is anticipated to be more common a scenario than fleas spreading bubonic plague, referred to as the Optional Postposed Indefinite Article Noun Phrase (OPIANP). The central question is whether there is semantic motivation for this postposition of the indefinite article. The results suggest that there is such motivation, namely that the OPIANP could be an extension of a more frequent construction identified as the Postposed Indefinite Article Noun Phrase (PIANP). It is shown that the pattern’s semantics is unpredictable from its component parts and that its primary function is to position already given arguments on an adjectival scale, thus foregrounding scalar qualities and backgrounding the nominal meaning. These findings are then discussed in light of current grammatical theory, and some suggestions are made for future research.
Modification and constructional blends in the use of proper names
Authors: Dancygier Barbara
Published: February 2012

This paper discusses a range of attested examples of NPs in which proper names are preceded by articles, determiners, and adjectives, arguing that such instances do not constitute a change into a common noun category. On the basis of such examples, it is claimed that the meaning of proper names relies not on unique reference, but on frame metonymy. Frames evoked by proper names interact with NP constructions, yielding a range of uses driven by the discourse context. Further, it is shown how the use of modified proper names in copular constructions is best explained through the framework of blending and the concept of constructional compositionality (as defined in Dancygier and Sweetser 2005).
If and when it’s a construction …
Authors: Sullivan Karen
Published: February 2012

The current study documents and analyzes the previously unrecognized English if and when construction. This construction coordinates a conditional and a temporal conjunction, as in if and when P Q; Q until and unless P; and a wide range of other micro-constructions. The current study documents the various types of if and when constructions, examines their relation to temporal and conditional constructions, and analyzes their variations in form and meaning from a Construction Grammar perspective.
“Not a Mission Impossible”
Authors: Malthus Caroline , Lu Hongyan
Published: February 2012

In New Zealand, Bachelor of Nursing (BN) programmes have in recent years attracted large cohorts of students with English as an additional language (EAL). The authors, a lecturer on the BN and a learning development advisor, observed many students successfully achieving both the BN qualification and nursing registration status. Nevertheless the prevailing discourse around EAL students within this programme, elsewhere at the institution and to some extent in the literature seem to be a deficit model in which lacks, gaps, problems and barriers, especially in communication, often have received more attention than acquired skills. This paper reports on a semi-structured retrospective interview-based study which explored the strategies and factors which in their own views helped 8 BN graduates to develop spoken language. We found that the interaction of socio-cultural learning with personal agency and a proactive approach to learning in academic and workplace contexts seem to have helped these graduates successfully develop communication skills. We argue that positively-focused initiatives for staff and students on both socio-cultural and individual contributions to oral communication development could help other EAL students succeed.
The politeness of a disciplining text
Authors: Hostetler Margaret
Published: February 2012

This paper uses linguistic theories of politeness to shed light on the functioning of certain discourse features of the Early Middle English Ancrene Wisse. It has been suggested that Ancrene Wisse is generically impolite because of the presence of conventional misogynistic tropes; however, the nature of the text as a religious rule requires a stance in which face-threatening acts, such as admonishing, advising, and even condemning, are common. The text also exhibits clear politeness strategies, including affectionate direct addresses of readers and comments that explicitly exclude readers from the text’s admonishments. The pragmatic effect of integrating these politeness strategies with the genre’s regulatory requirements creates a complex discourse field for readers to compass but, in fact, may provide an ideal environment for the text and its readers to pursue the genre’s Christian ideals.
Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores
Authors: Roscioli Emanuele , Di Francesco Laura , Bolognesi Alessio , Giubettini Maria , Orlando Serena , Harel Amnon , Schininà Maria Eugenia , Lavia Patrizia
Published: February 2012

Importin-β is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-β regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which binds importin-α) inhibits mitotic spindle pole formation. The central region (harboring nucleoporin-binding sites) regulates microtubule dynamic functions and interaction with kinetochores. Importin-β interacts through this region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores. We show that this interaction continues after nuclear pore disassembly. Overexpression of importin-β, or of the nucleoporin-binding region, inhibited RANGAP1 recruitment to mitotic kinetochores, an event that is known to require microtubule attachment and the exportin CRM1. Co-expressing either importin-β–interacting RANBP2 fragments, or CRM1, restored RANGAP1 to kinetochores and rescued importin-β–dependent mitotic dynamic defects. These results reveal previously unrecognized importin-β functions at kinetochores exerted via RANBP2 and opposed by CRM1.
Structural analysis reveals features of the spindle checkpoint kinase Bub1–kinetochore subunit Knl1 interaction
Authors: Krenn Veronica , Wehenkel Annemarie , Li Xiaozheng , Santaguida Stefano , Musacchio Andrea
Published: February 2012

The function of the essential checkpoint kinases Bub1 and BubR1 requires their recruitment to mitotic kinetochores. Kinetochore recruitment of Bub1 and BubR1 is proposed to rely on the interaction of the tetratricopeptide repeats (TPRs) of Bub1 and BubR1 with two KI motifs in the outer kinetochore protein Knl1. We determined the crystal structure of the Bub1 TPRs in complex with the cognate Knl1 KI motif and compared it with the structure of the equivalent BubR1TPR–KI motif complex. The interaction developed along the convex surface of the TPR assembly. Point mutations on this surface impaired the interaction of Bub1 and BubR1 with Knl1 in vitro and in vivo but did not cause significant displacement of Bub1 and BubR1 from kinetochores. Conversely, a 62-residue segment of Bub1 that includes a binding domain for the checkpoint protein Bub3 and is C terminal to the TPRs was necessary and largely sufficient for kinetochore recruitment of Bub1. These results shed light on the determinants of kinetochore recruitment of Bub1.
Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore
Authors: Espeut Julien , Cheerambathur Dhanya K. , Krenning Lenno , Oegema Karen , Desai Arshad
Published: February 2012

Accurate chromosome segregation requires coordination between microtubule attachment and spindle checkpoint signaling at the kinetochore. The kinetochore-localized KMN (KNL-1/Mis12 complex/Ndc80 complex) network, which mediates microtubule attachment and scaffolds checkpoint signaling, harbors two distinct microtubule-binding activities: the load-bearing activity of the Ndc80 complex and a less well-understood activity in KNL-1. In this paper, we show that KNL-1 microtubule-binding and -bundling activity resides in its extreme N terminus. Selective perturbation of KNL-1 microtubule binding in Caenorhabditis elegans embryos revealed that this activity is dispensable for both load-bearing attachment formation and checkpoint activation but plays a role in checkpoint silencing at the kinetochore. Perturbation of both microtubule binding and protein phosphatase 1 docking at the KNL-1 N terminus additively affected checkpoint silencing, indicating that, despite their proximity in KNL-1, these two activities make independent contributions. We propose that microtubule binding by KNL-1 functions in checkpoint silencing by sensing microtubules attached to kinetochores and relaying their presence to eliminate generation of the checkpoint signal.
Phosphate Uptake by Phosphate-Starved Euglena
Authors: BLUM J. J.
Published: February 2012

Phosphate-deprived Euglena acquire the ability to rapidly in-corporate added phosphate and, also, synthesize an induced acid phosphatase localized in the pellicle. The phosphate uptake system is saturated at low concentrations of phosphate and is inhibited by dinitrophenol, by low temperature, by K+, Li+, and Na+ ions, and competitively by arsenate. The orthophosphate incorporated into the cell is rapidly converted into organic forms but enough remains unesterified to suggest that the uptake is an active transport process. The data do not rule out the possibility that the induced phosphatase is involved in the transport process.
Changes in Leucine-Specific sRNA after Infection of E. coli by Phages T2 and T4
Authors: POLLACK ROBERT E.
Published: February 2012

Normal development of T2 and T4 in E. coli can occur without major alterations of the leucyl-specific sRNA contingent of the bacterium. The minor changes observed are apparently bacterial strain-specific. They show no temporal relation to the shift from early to late function in normal phage development.
Na Transport across Frog Skin at Low External Na Concentrations
Authors: BIBER THOMAS U. L. , CHEZ RONALD A. , CURRAN PETER F.
Published: February 2012

Isolated frog skin was bathed with a dilute solution containing 1 mm NaCl on the outside and with normal Ringer’s solution on the inner surface. Net Na flux was determined by simultaneous measurement of unidirectional fluxes with Na22 and Na24 and intracellular electrical potentials were examined with microelectrodes. There was a net inward transport of Na under both open-circuit and short-circuit conditions. The short-circuit current was approximately 15% greater than the net Na flux; the discrepancy could be accounted for by a small outward flux of Cl. The electrical potential profile did not differ greatly from that observed in skins bathed on the outside with normal Ringer’s solution. Under open-circuit conditions, there were usually several potential steps and under short-circuit conditions the cells were negative relative to the bathing solutions. Estimates of epithelial Na concentrations utilizing radioactive Na suggested that if all epithelial Na were in a single compartment, an active entry step would be necessary to allow a net inward Na transport. The results could also be explained by a series arrangement of Na compartments without necessarily postulating an active Na entry. The behavior of the potential profile suggested that this latter alternative was more likely.
In Vivo Studies on Fast and Slow Muscle Fibers in Cat Extraocular Muscles
Authors: BACH-y-RITA PAUL , ITO FUMIO
Published: February 2012

In anesthetized in vivo preparations, responses of two types of extraocular muscle fibers have been studied. The small, multiply innervated slow fibers have been shown to be capable of producing propagated impulses, and thus have been labeled slow multi-innervated twitch fibers. Fast and slow multi-innervated twitch fibers are distinguished by impulse conduction velocities, by ranges of membrane potentials, by amplitudes and frequencies of the miniature end plate potentials, by responses to the intravenous administration of succinylcholine, by the frequency of stimulation required for fused tetanus, and by the velocities of conduction of the nerve fibers innervating each of the muscle fiber types.
Calcium Distribution and Exchange in the Rat Uterus
Authors: van BREEMEN CASEY , DANIEL E. E. , van BREEMEN DIANNE
Published: February 2012

The calcium content and distribution of the rat uterus were determined employing flame photometry and Ca45 determinations. The total uterine calcium concentration was found to be 2.25 millimoles (mmoles) per kilogram wet weight, 0.45 of which was inexchangeable. The exchangeable Ca could be divided into 0.8 mmole/kg wet weight extracellular and 1.0 mmole/kg wet weight intracellular. The concentration of ionic Ca in rat serum was obtained by equilibrium dialysis as 1.5 mM or 53 % of the total serum Ca. The observed Ca distribution required that its active transport be postulated, since the membrane was shown to be permeable to Ca and the internal Ca concentration was far below its electrochemical equilibrium value. Metabolic inhibition by iodoacetate or dinitrophenol caused a net Ca uptake, but cooling to 4°C and ouabain did not. Iodoacetate did not affect the Ca45 efflux, but did increase the influx, suggesting that active Ca transport is accomplished by an exclusion mechanism. In experiments with varied external sodium concentrations, no evidence was obtained that sodium competes with calcium for inward transport. Cellular Ca binding was measured under conditions of prolonged metabolic inhibition, which abolished both active transport and the membrane potential. The association constants obtained were compatible with intracellular Ca binding to proteins, but insufficient to account for the low level of intracellular ionic Ca believed essential for relaxation. Hence metabolically dependent intracellular Ca binding was postulated. The Ca45 efflux was slowed down by Ca-free efflux media. The presence of Sr or EDTA could completely prevent this decrease in efflux rate, and Ba could partly prevent it. Changes in Mg and Na concentration did not affect the rate of Ca45 efflux. A model to explain Ca exchange across smooth muscle membranes has been proposed.