bluuebunny/crossref_metadata_2025 huggingface dataset:
ON PARALLEL SYSTEMS WITH HETEROGENEOUS GAMMA COMPONENTS
Authors: Zhao Peng
Published: May 2011

In this article, we study ordering properties of lifetimes of parallel systems with two independent heterogeneous gamma components in terms of the likelihood ratio order and the hazard rate order. LetX1andX2be two independent gamma random variables withXihaving shape parameterr>0 and scale parameter λi,i=1, 2, and letX*1andX*2be another set of independent gamma random variables withX*ihaving shape parameterrand scale parameter λ*i,i=1, 2. Denote byX2:2andX*2:2the corresponding maximum order statistics, respectively. It is proved that, among others, if (λ1, λ2) weakly majorize (λ*1, λ*2), thenX2:2is stochastically greater thanX*2:2in the sense of likelihood ratio order. We also establish, among others, that if 0<r≤1 and (λ1, λ2) isp-larger than (λ*1, λ*2), thenX2:2is stochastically greater thanX*2:2in the sense of hazard rate order. The results derived here strengthen and generalize some of the results known in the literature.
Vocabulary development in Greek children: a cross-linguistic comparison using the Language Development Survey*
Authors: PAPAELIOU CHRISTINA F. , RESCORLA LESLIE A.
Published: May 2011

This study investigated vocabulary size and vocabulary composition in Greek children aged 1 ; 6 to 2 ; 11 using a Greek adaptation of Rescorla's Language Development Survey (LDS; Rescorla, 1989). Participants were 273 toddlers coming from monolingual Greek-speaking families. Greek LDS data were compared with US LDS data obtained from the instrument's normative sample (Achenbach & Rescorla, 2000). Vocabulary size increased markedly with age, but Greek toddlers appeared to get off to a slower start in early word learning than US children. The correlation between percentage word use scores in Greek and US samples was moderate in size, indicating considerable overlap but some differences. Common nouns were the largest category among the fifty most frequent words in both samples. Numbers of adjectives and verbs were comparable across languages, but people and closed-class words were more numerous in the Greek sample. Finally, Greek late talkers showed similar patterns of vocabulary composition to those observed in typically developing Greek children.
Wide dissemination of extended-spectrum beta-lactamase (ESBL)-producingEscherichia coliandKlebsiellaspp. in acute care and rehabilitation hospitals
Authors: KOHLENBERG A. , SCHWAB F. , RÜDEN H.
Published: May 2011

A prospective surveillance system for extended-spectrum beta-lactamase-producingEscherichia coli(ESBL-E) and ESBL-producingKlebsiellaspp. (ESBL-K) was implemented in 39 German hospitals with the aim of determining the incidence densities (IDs) of community-onset and hospital-onset cases and of identifying risk factors for high IDs of hospital-onset cases. During 2008, 2081 ESBL-E/K cases were documented. ESBL-E cases (n=1330, 63·9%) were more common than ESBL-K cases (n=751, 36·1%), but a higher proportion of ESBL-K cases (59%) than of ESBL-E cases (39·5%) were hospital-onset cases. The mean IDs were 0·54 (range 0–2·53) per 1000 patient-days for all ESBL-EK cases, 0·29 (range 0–1·81) per 1000 patient-days for community-onset ESBL-EK cases and 0·25 (range 0–1·82) per 1000 patient-days for hospital-onset ESBL-EK cases. Regression analysis showed a linear association between the IDs of community-onset and hospital-onset cases. The wide dissemination of ESBL-E and ESBL-K emphasizes the need for hospital-wide surveillance to guide control measures.
Homogenisation of a locally periodic medium with areas of low and high diffusivity
Authors: VAN NOORDEN T. L. , MUNTEAN A.
Published: May 2011

We aim at understanding transport in porous materials consisting of regions with both high and low diffusivities. We apply a formal homogenisation procedure to the case wherethe heterogeneities are not arranged in a strictly periodic manner. The result is a two-scale model formulated inx-dependent Bochner spaces. We prove the weak solvability of the limit two-scale model for a prototypical advection–diffusion system of minimal size. A special feature of our analysis is that most of the basic estimates (positivity,L∞-bounds, uniqueness, energy inequality) are obtained in thex-dependent Bochner spaces.
Development of the outflow tracts with reference to aortopulmonary windows and aortoventricular tunnels
Authors: Anderson Robert H. , Cook Andrew , Brown Nigel A. , Henderson Deborah J. , Chaudhry Bill , Mohun Timothy
Published: May 2011

Although malformations involving the ventricular outflow tracts are often described as conotruncal malformations, there is no consensus as to the lesions included in, or excluded from, this category, reflecting, in part, the current lack of precise definitions of the embryonic truncus and conus. Analysis of development of the outflow tract in terms of proximal, intermediate, and distal components greatly facilitates understanding of the morphology of the aortopulmonary window and aortoventricular tunnels. The aortopulmonary windows reflect failure to close the embryonic aortopulmonary foramen, the space between the distal end of the cushions that divide the lumen of the outflow tract itself and the dorsal wall of the aortic sac. The aortopulmonary tunnels are produced subsequent to abnormal development of the cushions themselves. The distal ends of these cushions excavate to produce the sinuses and leaflets of the arterial valves. The proximal parts of the cushions muscularise to form the subpulmonary infundibulum. The middle part of the cushion mass disappears to provide a tissue plane between the infundibulum and the aortic root. Abnormal formation of this area accounts for the various types of aortoventricular tunnel. In our brief review, we show how the anatomy of these lesions correlates with development of the outflow tract.
Simple sequence repeat (SSR) markers for Elymus, Pseudoroegneria and Pascopyrum species (Triticeae: Gramineae)
Authors: Mott I. W. , Larson S. R. , Bushman B. S.
Published: May 2011

The Triticeae tribe (Poaceae) includes several important cereal crops, cultivated forages, annual and perennial grass weeds and ecologically diverse native North American grasses. Elymus L. is the largest and most complex genus in the Triticeae tribe with approximately 150 polyploid perennial grass species occurring worldwide. The genomic constitutions of approximately 40% of the Elymus species are unknown. Molecular markers are needed to facilitate genetic analysis of diversity and functional traits in these species. We have developed simple sequence repeat (SSR) markers for use in Elymus based on Elymus expressed sequence tag sequences. To test the polymorphic content and transferability of these SSRs, 100 SSR primer pairs were tested on 84 plants representing seven North American Elymus, Pseudoroegneria and Pascopyrum species. The number of bands produced from each of the SSRs ranged from 1 to 11 with an average of 4.3 bands/SSR. A subset of the 23 most polymorphic SSRs produced 142 bands, an average of 6.2 bands/SSR. Binary data from the 100 SSRs successfully separated all individuals into their respective accessions in a neighbour-joining phylogram with a 100% confidence interval. Analysis of molecular variance showed that 29.9% of the total variation was within and 70.1% was among the accessions. These SSRs will be a useful tool for investigating genetic diversity, genome constitutions and molecular mapping in Elymus and other Triticeae grasses.
A sail-backed suchian from the Heshanggou Formation (Early Triassic: Olenekian) of China
Authors: Nesbitt Sterling J. , Liu Jun , Li Chun
Published: May 2011

The two major lineages of extant archosaurs, crocodylians and avians, diverged in the Triassic, but the details and timing of this event are incompletely understood. Fragmentary and phylogenetically uninformative specimens, in addition to poor temporal constraints on rock units from the Early and Middle Triassic, typify obstacles in identifying early archosaurs. This paper re-describes the partial skeleton of the only known specimen of Xilousuchus sapingensis Wu, 1981 from the Early Triassic Heshanggou Formation in north-central China. Originally assigned to the non-archosaurian archosauriform clade Proterosuchidae, an extensive phylogenetic analysis posits X. sapingensis as a crown-group archosaur within Suchia, thus making this taxon the unequivocally oldest known member of Archosauria. The age and phylogenetic position of X. sapingensis indicate that many archosaurs, including all major clades of non-archosaurian archosauriforms, the avianline, ornithosuchids, aetosaurs and paracrocodylomorph lineages, must have diverged by the end of the Early Triassic. X. sapingensis is part of a possible clade of sail-backed poposauroids that were common components of archosaur assemblages during the Early to Middle Triassic.
Evaluating hypotheses for the early diversification of dinosaurs
Authors: Irmis Randall B.
Published: May 2011

Many hypotheses have been proposed for the rise of dinosaurs, but their early diversification remains poorly understood. This paper examines the occurrences, species diversity and abundance of early dinosaurs at both regional and global scales to determine patterns of their early evolutionary history. Four main patterns are clear: (1) sauropodomorph dinosaurs became abundant during the late Norian–Rhaetian of Gondwana and Europe; (2) Triassic dinosaurs of North America have low species diversity and abundance until the beginning of the Jurassic; (3) sauropodomorphs and ornithischians are absent in the Triassic of North America; and (4) ornithischian dinosaurs maintain low species diversity, relative abundance and small body size until the Early Jurassic. No one hypothesis fully explains these data. There is no evidence for a Carnian–Norian extinction event, but sauropodomorphs did become abundant during the Norian in some assemblages. No clear connection exists between palaeoenvironment and early dinosaur diversity, but environmental stress at the Triassic–Jurassic boundary is consistent with changes in North American dinosaur assemblages. Elevated growth rates in dinosaurs are consistent with the gradual phyletic increase in body size. This study demonstrates that early dinosaur diversification was a complex process that was geographically diachronous and probably had several causes.
A reassessment of the basal dinosaur Guaibasaurus candelariensis, from the Late Triassic Caturrita Formation of south Brazil
Authors: Langer Max C. , Bittencourt Jonathas S. , Schultz Cesar L.
Published: May 2011

The dinosaur record of the Santa Maria beds of Rio Grande do Sul (Mid–Late Triassic; south Brazil) includes the herrerasaur Staurikosaurus pricei, and two basal members of the sauropodomorph lineage: Saturnalia tupiniquim and Unaysaurus tolentinoi. The most enigmatic of the saurischian taxa is, however, Guaibasaurus candelariensis, previously regarded as either a basal theropod or a basal sauropodomorph. This study provides a detailed anatomical revision of all specimens originally referred to G. candelariensis by Bonaparte and co-authors, including its type-series and a more recently excavated partial postcranium. Although coming from different sites, these specimens share a unique combination of traits, and at least one possible autapomorphic feature of the pelvis, which support the inclusivity and uniqueness of the species. G. candelariensis was a medium-sized (nearly 2 m long) biped with an intriguing mix of plesiomorphic and derived (eusaurischian/theropod) features. Phylogenetic studies reveal weak support for the nesting of G. candelariensis within Theropoda, but this affinity is bolstered by various traits it shares with neotheropods. The Norian age of G. candelariensis corroborates previous studies that suggest the continuous radiation of more basal dinosauromorphs until the end of the Triassic, after the appearance of the three main dinosaur clades.
Preface to ‘Late Triassic Terrestrial Biotas and the Rise of Dinosaurs’ Special Issue
Authors: Butler Richard J. , Irmis Randall B. , Langer Max C.
Published: May 2011

The early Mesozoic records an important transition in the history of the Earth’s terrestrial ecosystems. As they recovered from the largest known mass extinction (the end-Permian event), organisms in these ecosystems transitioned to new forms that eventually evolved into the classic Mesozoic biotas, and laid the foundations for many groups still flourishing today (Fraser 2006; Irmis & Whiteside 2010; Sues & Fraser 2010). All of this was set against a backdrop of dynamic climatic and physical events that shaped these biotas. This early Mesozoic terrestrial transition reached its culmination in many ways during the Late Triassic, when ecosystems had largely recovered from the end-Permian extinction, but had not yet been affected by the end-Triassic mass extinction (Fraser & Sues this volume). Thus, we see a combination of taxa, with some groups that would not survive the end of the Triassic living alongside early representatives of lineages that flourished later in the Mesozoic (e.g., Fraser 2006; Irmis et al. 2007; Brusatte et al. 2008; Sues & Fraser 2010, this volume) and in some cases are still diverse today. Just one example of this transition, recorded during the Late Triassic, is the origin and diversification of non-avian dinosaurs, the iconic representatives of Mesozoic terrestrial ecosystems (Brusatte et al. 2010; Langer et al. 2010). Although small and rare components of their respective biotas when they first evolved ∼231 Ma, dinosaurs were abundant and had a near-worldwide distribution by the beginning of the Jurassic Period (∼201·3 Ma).
Evaluation des neuropsychologischen Gruppenprogramms ATTENTIONER zur Aufmerksamkeitstherapie bei Kindern und Jugendlichen
Authors: Tischler Lars , Karpinski Norbert , Petermann Franz
Published: May 2011

Das neuropsychologische Gruppentraining ATTENTIONER zur Behandlung von Kindern und Jugendlichen mit Aufmerksamkeitsstörungen ermöglicht die gezielte Therapie der Aufmerksamkeitssteuerung. Die vorliegende Studie untersucht an einer Stichprobe von N = 17 Jungen und Mädchen im Alter von sieben bis 13 Jahren, die am ATTENTIONER-Training teilgenommen haben, mittels der TAP Veränderungen in der Aufmerksamkeitssteuerung (Geteilte Aufmerksamkeit und Go/Nogo ½) in einem Prä-Prä-Post Design. Neben Verbesserungen in der parallelen Reizverarbeitung konnte insbesondere die Inhibitionsfähigkeit der Kinder deutlich gesteigert werden. Dies ist von besonderer Bedeutung für die Rolle impulsiven Verhaltens etwa bei Störungen des Sozialverhaltens.
Der Einfluss von Schlaganfällen im Kindes- und Jugendalter auf die kognitive Entwicklung
Authors: Daseking Monika , Petermann Franz
Published: May 2011

Schlaganfälle ereignen sich im Kindesalter nur selten, haben jedoch für betroffene Kinder große Auswirkungen auch auf kognitive Fähigkeiten. Die vorliegende Studie analysiert die Intelligenzleistung von 103 Kindern nach einem Schlaganfall im Versorgungsgebiet der Arteria cerebri media. Dabei zeigt sich, dass das Alter zum Zeitpunkt der Schädigung einen großen Einfluss auf das Leistungsniveau hat. Kinder mit perinatalen Schlaganfällen schneiden in den Intelligenztestskalen insgesamt am schlechtesten ab. Dabei weist eine antikonvulsive Medikation zur Epilepsiebehandlung einen zusätzlichen Effekt auf. Ereignet sich der Schlaganfall nach dem sechsten Lebensjahr, können lateralisierte Effekte sichtbar gemacht werden: nach linkshemisphärischen Infarkten zeigen sich Sprachleistungen reduziert, rechtshemisphärische Schlaganfälle wirken sich auf visuell-räumliche Leitungen aus. Die Ergebnisse weisen auf die Notwendigkeit langfristiger neuropsychologischer Begleitung der Kinder und Jugendlichen hin.
Was wissen wir über Langzeiteffekte von Methylphenidatbehandlung auf die Hirnentwicklung von Kindern und Jugendlichen mit einer Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS)?
Authors: Gilsbach Susanne , Günther Thomas , Konrad Kerstin
Published: May 2011

Obwohl Psychostimulanzien zu den Behandlungsmethoden der ersten Wahl bei Kindern mit einer Aufmerksamkeitsdefizit/-Hyperaktivitätsstörung (ADHS) im Kindes- und Jugendalter gehören, sind mögliche Langzeitfolgen einer Stimulanzientherapie noch nicht ausreichend erforscht. Während eine kurzzeitige positive Wirkung von Stimulanzien auf Aufmerksamkeitsleistungen als gesichert gilt, sind die langfristigen Auswirkungen insbesondere einer Medikation in der frühen Kindheit sowie einer Dauermedikation noch weitestgehend unbekannt. Verschiedene Studien ergaben Hinweise auf einen Einfluss einer Dauermedikation mit Stimulanzien sowohl auf die strukturelle als auch auf funktionelle Hirnentwicklung. Des Weiteren sollten mögliche unerwünschte kognitive und motivationale Nebenwirkungen einer Medikation mit Methylphenidat genauer in Betracht gezogen werden. Insgesamt zeigt sich die Datenlage heterogen und es mangelt an Studien mit ausreichend großen Fallzahlen.
Kortikale Informationsverarbeitungsprozesse bei Vätern von Kindern mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS): eine Pilotstudie mit langsamen Hirnpotenzialen
Authors: Gerber Wolf-Dieter , Darabaneanu Stephanie , Dumpert Hans-Dieter , Müller Gabriele Gerber-von , Kowalski Jens T. , Kropp Peter , Niederberger Uwe , Siniatchkin Michael , Petermann Franz
Published: May 2011

Hintergrund/Fragestellung: ADHS wird als eine womöglich genetisch bedingte Störung der kortikalen Informationsverarbeitung im Kindes- und Jugendalter, die bei mehr als zwei Drittel der Betroffenen auch im Erwachsenenalter andauert, beschrieben. Wenig bekannt ist über die kortikale Informationsverarbeitung und Aufmerksamkeitsbereitschaft von Vätern von Kindern mit ADHS. In der vorliegenden Studie sollten daher Väter von ADHS-Kindern mit gesunden Kontrollen hinsichtlich ihrer kortikalen Aufmerksamkeitsbereitschaft verglichen werden. Patienten und Methoden: 14 Väter von ADHS-Kindern im Alter von 24 bis 62 Jahren (M = 39,4 Jahre) wurden mit 14 Vätern von gesunden Kindern (M = 36,7 Jahre) verglichen. Die kortikale Aufmerksamkeitsbereitschaft wurde mittels Contingente Negative Variation (CNV) in einem zwei Stimulusparadigma (Go/NoGo; Cz, Fz) mit einem Intervall von 3 Sekunden gemessen. Die ADHS-Kernsymptome wurden mittels spezifischer Fragebögen erfasst. Ergebnisse: Die CNV-Reaktionszeiten der ADHS-Väter waren signifikant langsamer als die der gesunden Kontrollgruppe. Zudem ergab sich eine deutlich beschleunigte Habituation, während sich die CNV-Amplituden im Cervix-Potenzial statistisch nicht von den Gesunden unterschieden. Dagegen zeigte sich frontal eine signifikant stärkere Negativierung der ADHS-Väter. Schlussfolgerung: Väter von ADHS-Kindern zeigen in den langsamen Hirnpotenzialen ähnliche Auffälligkeiten, wie sie auch bei Kindern nachweisbar sind. Die erkennbare gestörte kortikale Informationsverarbeitung könnte sowohl als Hinweis einer genetischen Disposition, als auch epigenetischer Determination denkbar sein.
Mast cells reside in myometrium and cervix, but are dispensable in mice for successful pregnancy and labor
Authors: Menzies Fiona M , Higgins Claire A , Shepherd Malcolm C , Nibbs Robert JB , Nelson Scott M
Published: May 2011

Parturition is associated with myometrial and cervical inflammation. The causes and consequences of this inflammatory response are not clear. Mast cells (MCs) are important inducers of allergic and non‐allergic inflammation, and their secreted products can induce myometrial contractions. Thus, mast cell activation has been hypothesized to have a role in initiating labor and/or driving labor‐associated inflammation. We report that small numbers of MCs expressing chymase and tryptase are present in the myometrium and cervix of pregnant women. Labor did not lead to any change in mast cell abundance in these tissues, but was associated with reduced expression of the mast‐cell regulator FcεR1A, indicative of a change in mast cell properties. This coincided with contraction‐dependent myocyte production of interleukin‐10 (IL‐10), a known suppressor of FcεR1A expression. MCs were also found in the uterine horn and cervical region of pregnant C57BL/6 mice, increasing in number in the cervix, but not the myometrium, with labor. As expected, these cells were absent from mast‐cell‐deficient KitW−sh mice. Nonetheless, pregnant KitW−sh mice showed no defects in the timing of labor induction or in the upregulation of leukocyte markers during labor. Thus, MCs are present in the uterus and cervix of humans and mice, and our mouse studies suggest that they do not have a vital role in the induction of labor, or in the promotion of labor‐associated inflammation.
Development of a mobile magnetic resonance imaging system for outdoor tree measurements
Authors: Kimura Takeshi , Geya Yuto , Terada Yasuhiko , Kose Katsumi , Haishi Tomoyuki , Gemma Hiroshi , Sekozawa Yoshihiko
Published: May 2011

By combining a 0.3 T permanent magnet with flexible rotation and translation mechanism, a probe with a local electromagnetic shielding, several electrical units, a mobile lift, and an electric wagon, a mobile magnetic resonance imaging (MRI) system was developed for outdoor tree measurements. 2D cross-sectional images of normal and diseased branches of a pear tree were acquired for measurements of T1, T2, proton density, and apparent diffusion constant (ADC). The ADC map clearly differentiated diseased from normal branches. A whole-day measurement of the ADC map demonstrated that microscopic water flow in the normal branch changed proportionally with solar radiation. Therefore, we have concluded that our mobile MRI system is a powerful tool for studies of plants in outdoor environments.
‘The Stone in the Air’: Paul Celan's other Terrain
Authors: Groves Jason
Published: May 2011

Literary writing has operated as a space of inquiry unsettling the literal and figurative ground on which thinking takes place. From Hölderlin's invocations to the ether, to Walter Benjamin's characterization of Baudelaire's poetry as unfathomable, a certain tradition of writing, particularly in German letters, takes shape around a critique of gravity. Against the background of a geopoetics, I propose to turn to the question of an inconstant and inconsistent ground in Paul Celan's ‘geological lyric’ by explicating the relationship in his writing between the earth and its unthought other: air. This reading has as its object of inquiry what I am calling Celan's aerography, which is doubly articulated in the turn to aerial space in his poetry and in his articulation of the work of air in those terrestrial landscapes formed and deformed by aeolian processes. I argue that the radically dissipative geographies evoked in his poems could extend critical geographic inquiry into a multiple and turbulent materiality; however, the sheer spectrality of the material world in Celan's poetry seems to require an (a)material criticism, that is, a materiality without matter.
Bunkerology—A Case Study in the Theory and Practice of Urban Exploration
Authors: Bennett Luke
Published: May 2011

This paper reviews existing academic interpretations of ‘urban exploration’ and argues that focus to date on identifying and celebrating the transgressive and/or emancipatory dimension of this practice has failed to account for the taxonomic and survey-related orientation evident in the author's study of accounts of exploration of Cold War bunkers posted on urban exploration Internet forums. The author's study suggests that the survey and veneration of place evident in these accounts may be a more significant motivation for urban exploration as practised than psychogeographical revere and/or transgressive incursion into space and place.
Role of mother's genes and environment in postpartum depression
Authors: Mitchell Colter , Notterman Daniel , Brooks-Gunn Jeanne , Hobcraft John , Garfinkel Irwin , Jaeger Kate , Kotenko Iulia , McLanahan Sara
Published: May 2011

Most studies of human molecular genetics and social environment interactions on health have relied heavily on the classic diathesis-stress model that treats genetic variations and environments as being either “risky” or “protective.” The biological susceptibility model posits that some individuals have greater genetic reactivity to stress, leading to worse outcomes in poor environments, but better outcomes in rich environments. Using a nontruncated measure of a chronic environmental stressor—socioeconomic status—measured by education, and two polymorphisms (5-HTTLPR and STin2 VNTR) of the serotonin transporter gene (
5-HTT
), we find strong evidence that some women are genetically more reactive to the environment, resulting in a crossover of risks of postpartum depression for the most reactive groups. We discuss how our approach and findings provide a framework for understanding some of the confusion in the gene-environment interaction literature on stress,
5-HTT
, and depression.
Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window
Authors: Welsher Kevin , Sherlock Sarah P. , Dai Hongjie
Published: May 2011

Fluorescent imaging in the second near-infrared window (NIR II, 1–1.4 μm) holds much promise due to minimal autofluorescence and tissue scattering. Here, using well-functionalized biocompatible single-walled carbon nanotubes (SWNTs) as NIR II fluorescent imaging agents, we performed high-frame-rate video imaging of mice during intravenous injection of SWNTs and investigated the path of SWNTs through the mouse anatomy. We observed in real-time SWNT circulation through the lungs and kidneys several seconds postinjection, and spleen and liver at slightly later time points. Dynamic contrast-enhanced imaging through principal component analysis (PCA) was performed and found to greatly increase the anatomical resolution of organs as a function of time postinjection. Importantly, PCA was able to discriminate organs such as the pancreas, which could not be resolved from real-time raw images. Tissue phantom studies were performed to compare imaging in the NIR II region to the traditional NIR I biological transparency window (700–900 nm). Examination of the feature sizes of a common NIR I dye (indocyanine green) showed a more rapid loss of feature contrast and integrity with increasing feature depth as compared to SWNTs in the NIR II region. The effects of increased scattering in the NIR I versus NIR II region were confirmed by Monte Carlo simulation. In vivo fluorescence imaging in the NIR II region combined with PCA analysis may represent a powerful approach to high-resolution optical imaging through deep tissues, useful for a wide range of applications from biomedical research to disease diagnostics.
Control ofToxoplasmareactivation by rescue of dysfunctional CD8+T-cell response via PD-1–PDL-1 blockade
Authors: Bhadra Rajarshi , Gigley Jason P. , Weiss Louis M. , Khan Imtiaz A.
Published: May 2011

In this study, we document thatToxoplasma gondiidifferentiation and reactivation are mediated by systemic CD8 T-cell dysfunction during chronic infection. We demonstrate that CD8+T-cell exhaustion occurs despite control of parasitemia during early-chronic toxoplasmosis. During later phases, these cells become exhausted, leading to parasite reactivation and mortality. Concomitant with increased CD8+T-cell apoptosis and decreased effector response, this dysfunction is characterized by a graded elevation in expression of inhibitory receptor PD-1 on these cells in both lymphoid and nonlymphoid tissue. Blockade of the PD-1–PDL-1 pathway reinvigorates this suboptimal CD8+T-cell response, resulting in control of parasite reactivation and prevention of mortality in chronically infected animals. To the best of our knowledge, this report is unique in showing that exposure to a persistent pathogen despite initial control of parasitemia can lead to CD8+T-cell dysfunction and parasite reactivation.
Doublesex and mab-3–related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate
Authors: Gennet Nicole , Gale Emily , Nan Xinsheng , Farley Emma , Takacs Katalin , Oberwallner Barbara , Chambers David , Li Meng
Published: May 2011

Understanding the control of cell-fate choices during embryonic stem cell (ESC) differentiation is crucial for harnessing strategies for efficient production of desired cell types for pharmaceutical drug screening and cell transplantation. Here we report the identification of the zinc finger-like doublesex and mab-3–related transcription factor 5 (Dmrt5) as a marker for mammalian ventral-medial mesencephalic neuroepithelium that give rise to dopamine neurons. Gain- and loss-of-function studies in ESC demonstrate that Dmrt5 is critically involved in the specification of ventral-medial neural progenitor cell fate and the subsequent generation of dopamine neurons expressing essential midbrain characteristics. Genome-wide analysis of Dmrt5-mediated transcriptome changes and expression profiling of ventral-medial and ventral-lateral mesencephalic neuroepithelium revealed suppressive and inductive regulatory roles for Dmrt5 in the transcription program associated with the ventral-medial neural progenitor fates. Together, these data identify Dmrt5 as an important player in ventral mesencephalic neural fate specification.
Using luminosity data as a proxy for economic statistics
Authors: Chen Xi , Nordhaus William D.
Published: May 2011

A pervasive issue in social and environmental research has been how to improve the quality of socioeconomic data in developing countries. Given the shortcomings of standard sources, the present study examines luminosity (measures of nighttime lights visible from space) as a proxy for standard measures of output (gross domestic product). We compare output and luminosity at the country level and at the 1° latitude × 1° longitude grid-cell level for the period 1992–2008. We find that luminosity has informational value for countries with low-quality statistical systems, particularly for those countries with no recent population or economic censuses.
Committed sea-level rise for the next century from Greenland ice sheet dynamics during the past decade
Authors: Price Stephen F. , Payne Antony J. , Howat Ian M. , Smith Benjamin E.
Published: May 2011

We use a three-dimensional, higher-order ice flow model and a realistic initial condition to simulate dynamic perturbations to the Greenland ice sheet during the last decade and to assess their contribution to sea level by 2100. Starting from our initial condition, we apply a time series of observationally constrained dynamic perturbations at the marine termini of Greenland’s three largest outlet glaciers, Jakobshavn Isbræ, Helheim Glacier, and Kangerdlugssuaq Glacier. The initial and long-term diffusive thinning within each glacier catchment is then integrated spatially and temporally to calculate a minimum sea-level contribution of approximately 1 ± 0.4 mm from these three glaciers by 2100. Based on scaling arguments, we extend our modeling to all of Greenland and estimate a minimum dynamic sea-level contribution of approximately 6 ± 2 mm by 2100. This estimate of committed sea-level rise is a minimum because it ignores mass loss due to future changes in ice sheet dynamics or surface mass balance. Importantly, > 75% of this value is from the long-term, diffusive response of the ice sheet, suggesting that the majority of sea-level rise from Greenland dynamics during the past decade is yet to come. Assuming similar and recurring forcing in future decades and a self-similar ice dynamical response, we estimate an upper bound of 45 mm of sea-level rise from Greenland dynamics by 2100. These estimates are constrained by recent observations of dynamic mass loss in Greenland and by realistic model behavior that accounts for both the long-term cumulative mass loss and its decay following episodic boundary forcing.
Thermodynamic stability of small hairpin RNAs highly influences the loading process of different mammalian Argonautes
Authors: Gu Shuo , Jin Lan , Zhang Feijie , Huang Yong , Grimm Dirk , Rossi John J. , Kay Mark A.
Published: May 2011

MicroRNAs and siRNAs interact with target sequences in mRNAs, inducing cleavage- and non-cleavage–based gene repression through the RNA-induced silencing complex (RISC) that consists of one of four mammalian Argonaute proteins, Ago1–Ago4. The process of how Dicer substrate small hairpin RNAs (shRNAs) are loaded into different mammalian Agos in vivo is not well established. Here we report that shRNAs are loaded into mammalian Agos in two stepwise processes, physical association and activation, with the latter being the rate-limiting step with noncleaving RISC. We establish that, although RNA duplexes processed from shRNAs bind to Agos in cells with similar affinity, the degree by which the complexes are activated (coupled with the removal of the passenger strand) correlates with the thermodynamic instability of RNA duplexes being loaded rather than the structure of the RNA, as was previously demonstrated inDrosophila. Interestingly, Ago loading of siRNAs is less sensitive to thermostability than that of their shRNA equivalents. These results may have important implications for the future design of RNAi-based therapeutics.
Cell-free sorting of peroxisomal membrane proteins from the endoplasmic reticulum
Authors: Agrawal Gaurav , Joshi Saurabh , Subramani Suresh
Published: May 2011

Several yeast and mammalian peroxisomal membrane proteins (PMPs) are delivered to peroxisomes via the endoplasmic reticulum (ER). Fluorescence microscopy showed a focused assembly of PMPs in a specialized domain of the ER, referred to as the preperoxisomal ER. It is proposed that preperoxisomal vesicles containing PMPs bud from this domain to either fuse with preexisting peroxisomes or to mature into functional peroxisomes by uptake of peroxisomal membrane and matrix proteins. However, such vesicular entities are not identified nor are the biochemical requirements for the budding process known. We developed an in vitro cell-free ER-budding assay using
Pichia pastoris
and followed two endogenous PMPs, Pex11p and Pex3p during their ER exit. Both the PMPs were copackaged in the ER-budded vesicles that float on a Nycodenz gradient. PMP budding from the ER was dependent on ATP, temperature, cytosol, and Pex19p and generated preperoxisomal vesicles with an incomplete complement of PMPs. Surprisingly, Pex11p budding was independent of Pex3p; however, the budded vesicles were devoid of most of the PMPs otherwise present in the wild-type vesicles and might represent peroxisomal remnants. Our findings provide a biochemical platform to uncover the mechanism of PMP budding from the ER.
Optimized clinical performance of growth hormone with an expanded genetic code
Authors: Cho Ho , Daniel Tom , Buechler Ying Ji , Litzinger David C. , Maio Zhenwei , Putnam Anna-Maria Hays , Kraynov Vadim S. , Sim Bee-Cheng , Bussell Stuart , Javahishvili Tsotne , Kaphle Sami , Viramontes Guillermo , Ong Mike , Chu Stephanie , GC Becky , Lieu Ricky , Knudsen Nick , Castiglioni Paola , Norman Thea C. , Axelrod Douglas W. , Hoffman Andrew R. , Schultz Peter G. , DiMarchi Richard D. , Kimmel Bruce E.
Published: May 2011

The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of
p
-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
Repair of injured proximal tubule does not involve specialized progenitors
Authors: Humphreys Benjamin D. , Czerniak Suzanne , DiRocco Derek P. , Hasnain Wirasat , Cheema Rabia , Bonventre Joseph V.
Published: May 2011

Recently we have established that the kidney tubular epithelium is repaired by surviving epithelial cells. It is not known, however, whether a population of intratubular adult progenitor cells are responsible for this epithelial repair after acute kidney injury. In this study, we used an unbiased DNA analog-based approach that does not rely on candidate markers to track multiple rounds of cell division in vivo. In the proximal tubule, robust thymidine analog incorporation was observed postinjury. Cell division was stochastic and enriched among cells that were injured and dedifferentiated. There was no evidence for the presence of a population of specialized progenitors that repeatedly divide in response to injury. Instead, these results indicate that after injury, new epithelial cells arise from self-duplication of surviving cells, most of which are injured. Because the renal papilla contains DNA label-retaining cells and has been proposed as a stem cell niche, we examined the proliferative behavior of these putative progenitors after ischemia-reperfusion injury. Although label-retaining cells in the renal papilla diminished with time after ischemia-reperfusion injury, they neither proliferated nor migrated to the outer medulla or cortex. Thus, nonlethally injured cells repopulate the kidney epithelium after injury in the absence of any specialized progenitor cell population.
Circadian oscillation of gibberellin signaling in
Arabidopsis
Authors: Arana María Verónica , Marín-de la Rosa Nora , Maloof Julin N. , Blázquez Miguel A. , Alabadí David
Published: May 2011

Circadian clocks are endogenous timekeeping mechanisms that allow organisms to anticipate rhythmic, daily environmental changes. Temporal coordination of transcription results in a set of gene expression patterns with peak levels occurring at precise times of the day. An intriguing question is how a single clock can generate different oscillatory rhythms, and it has been proposed that hormone signaling might act in plants as a relay mechanism to modulate the amplitude and the phase of output rhythms. Here we show that the circadian clock gates gibberellin (GA) signaling through transcriptional regulation of the GA receptors, resulting in higher stability of DELLA proteins during daytime and higher GA sensitivity at night. Oscillation of GA signaling appears to be particularly critical for rhythmic growth, given that constitutive expression of the GA receptor expands the daily growth period in seedlings, and complete loss of DELLA function causes continuous, arrhythmic hypocotyl growth. Moreover, transcriptomic analysis of a pentuple
della
KO mutant indicates that the GA pathway mediates the rhythmic expression of many clock-regulated genes related to biotic and abiotic stress responses and cell wall modification. Thus, gating of GA sensitivity by the circadian clock represents an additional layer of regulation that might provide extra robustness to the diurnal growth rhythm and constitute a regulatory module that coordinates the circadian clock with additional endogenous and environmental signals.
Inhibition of autoprocessing of natural variants and multidrug resistant mutant precursors of HIV-1 protease by clinical inhibitors
Authors: Louis John M. , Aniana Annie , Weber Irene T. , Sayer Jane M.
Published: May 2011

Self-cleavage at the N terminus of HIV-1 protease from the Gag-Pol precursor (autoprocessing) is crucial for stabilizing the protease dimer required for onset of mature-like catalytic activity, viral maturation, and propagation. Among nine clinical protease inhibitors (PIs), darunavir and saquinavir were the most effective in inhibiting wild-type HIV-1 group M precursor autoprocessing, with an IC50value of 1–2 μM, 3–5 orders of magnitude higher than their binding affinities to the corresponding mature protease. Accordingly, both group M and N precursor–PI complexes exhibitTms 17–21 °C lower than those of the corresponding mature protease–PI complexes suggestive of markedly reduced stabilities of the precursor dimer–PI ensembles. Autoprocessing of group N (natural variant) and three group M precursors bearing 11–20 mutations associated with multidrug resistance was either weakly responsive or fully unresponsive to inhibitors at concentrations up to a practical limit of approximately 150 μM PI. This observation parallels decreases of up to 8 × 103-fold (e.g., 5 pM to 40 nM) in the binding affinity of darunavir and saquinavir to mature multidrug resistant proteases relative to wild type, suggesting that inhibition of some of these mutant precursors will occur only in the high μM to mM range in extreme PI-resistance, which is an effect arising from coordinated multiple mutations. An extremely darunavir-resistant mutant precursor is more responsive to inhibition by saquinavir. These findings raise the questions whether clinical failure of PI therapy is related to lack of inhibition of autoprocessing and whether specific inhibitors can be designed with low-nM affinity to target autoprocessing.
Cytochrome P450 CYP94B3 mediates catabolism and inactivation of the plant hormone jasmonoyl-L-isoleucine
Authors: Koo Abraham J. K. , Cooke Thomas F. , Howe Gregg A.
Published: May 2011

The phytohormone jasmonoyl-L-isoleucine (JA-Ile) signals through the COI1-JAZ coreceptor complex to control key aspects of plant growth, development, and immune function. Despite detailed knowledge of the JA-Ile biosynthetic pathway, little is known about the genetic basis of JA-Ile catabolism and inactivation. Here, we report the identification of a wound- and jasmonate-responsive gene from
Arabidopsis
that encodes a cytochrome P450 (CYP94B3) involved in JA-Ile turnover. Metabolite analysis of wounded leaves showed that loss of CYP94B3 function in
cyp94b3
mutants causes hyperaccumulation of JA-Ile and concomitant reduction in 12-hydroxy-JA-Ile (12OH-JA-Ile) content, whereas overexpression of this enzyme results in severe depletion of JA-Ile and corresponding changes in 12OH-JA-Ile levels. In vitro studies showed that heterologously expressed CYP94B3 converts JA-Ile to 12OH-JA-Ile, and that 12OH-JA-Ile is less effective than JA-Ile in promoting the formation of COI1-JAZ receptor complexes. CYP94B3-overexpressing plants displayed phenotypes indicative of JA-Ile deficiency, including defects in male fertility, resistance to jasmonate-induced growth inhibition, and susceptibility to insect attack. Increased accumulation of JA-Ile in wounded
cyp94b3
leaves was associated with enhanced expression of jasmonate-responsive genes. These results demonstrate that CYP94B3 exerts negative feedback control on JA-Ile levels and performs a key role in attenuation of jasmonate responses.
How words can and cannot be learned by observation
Authors: Medina Tamara Nicol , Snedeker Jesse , Trueswell John C. , Gleitman Lila R.
Published: May 2011

Three experiments explored how words are learned from hearing them across contexts. Adults watched 40-s videotaped vignettes of parents uttering target words (in sentences) to their infants. Videos were muted except for a beep or nonsense word inserted where each “mystery word” was uttered. Participants were to identify the word. Exp. 1 demonstrated that most (90%) of these natural learning instances are quite uninformative, whereas a small minority (7%) are highly informative, as indexed by participants’ identification accuracy. Preschoolers showed similar information sensitivity in a shorter experimental version. Two further experiments explored how cross-situational information helps, by manipulating the serial ordering of highly informative vignettes in five contexts. Response patterns revealed a learning procedure in which only a single meaning is hypothesized and retained across learning instances, unless disconfirmed. Neither alternative hypothesized meanings nor details of past learning situations were retained. These findings challenge current models of cross-situational learning which assert that multiple meaning hypotheses are stored and cross-tabulated via statistical procedures. Learners appear to use a one-trial “fast-mapping” procedure, even under conditions of referential uncertainty.
The
Arabidopsis
flagellin receptor FLS2 mediates the perception of
Xanthomonas
Ax21 secreted peptides
Authors: Danna Cristian H. , Millet Yves A. , Koller Teresa , Han Sang-Wook , Bent Andrew F. , Ronald Pamela C. , Ausubel Frederick M.
Published: May 2011

Detection of microbes by plants relies in part on an array of pattern-recognition receptors that recognize conserved microbial signatures, so-called “microbe-associated molecular patterns.” The
Arabidopsis thaliana
receptor-like kinase FLS2 is the pattern-recognition receptor for bacterial flagellin. Similarly to FLS2, the rice transmembrane protein XA21 is the receptor for the sulfated form of the
Xanthomonas oryzae
pv.
oryzae
secreted protein Ax21. Here we show that Ax21-derived peptides activate
Arabidopsis
immunity, triggering responses similar to those elicited by flagellin, including an oxidative burst, induction of defense-response genes, and enhanced resistance to bacterial pathogens. To identify
Arabidopsis Xa21
functional homologs, we used a reverse genetics approach to screen T-DNA insertion mutants corresponding to all 47 of the
Arabidopsis
genes encoding non-RD kinases belonging to the interleukin-1 receptor-associated kinase (IRAK) family. Surprisingly, among all of these mutant lines, only
fls2
mutants exhibited a significant loss of response to Ax21-derived peptides. Ax21 peptides also failed to activate defense-related responses in an
fls2-24
mutant that does not bind Flg22. Moreover, a Flg22Δ2 variant of Flg22 that binds to FLS2 but does not activate FLS2-mediated signaling suppressed Ax21-derived peptide signaling, indicating mutually exclusive perception of Flg22 or Ax21 peptides by FLS2. The data indicate that FLS2 functions beyond flagellin perception to detect other microbe-associated molecular patterns.
Tissue plasminogen activator prevents white matter damage following stroke
Authors: Correa Fernando , Gauberti Maxime , Parcq Jérôme , Macrez Richard , Hommet Yannick , Obiang Pauline , Hernangómez Miriam , Montagne Axel , Liot Géraldine , Guaza Carmen , Maubert Eric , Ali Carine , Vivien Denis , Docagne Fabian
Published: May 2011

Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor–like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment.