bluuebunny/crossref_metadata_2025 huggingface dataset:
Marx, the Young Hegelians, and the Origins of Radical Social Theory
Authors: Breckman Warren
Published: March 2010

This is the first major study of Marx and the Young Hegelians in twenty years. The book offers a new interpretation of Marx's early development, the political dimension of Young Hegelianism, and that movement's relationship to political and intellectual currents in early nineteenth-century Germany. Warren Breckman challenges the orthodox distinction drawn between the exclusively religious concerns of Hegelians in the 1830s and the sociopolitical preoccupations of the 1840s. He shows that there are inextricable connections between the theological, political and social discourses of the Hegelians in the 1830s. The book draws together an account of major figures such as Feuerbach and Marx, with discussions of lesser-known but significant figures such as Eduard Gans, August Cieszkowski, Moses Hess, F. W. J. Schelling as well as such movements as French Saint-Simonianism and 'positive philosophy'. Wide-ranging in scope and synthetic in approach, this is an important book for historians of philosophy, theology, political theory and nineteenth-century ideas.
An Introduction to Magnetohydrodynamics
Authors: Davidson P. A.
Published: March 2010

Magnetic fields influence many natural and man-made flows. They are routinely used in industry to heat, pump, stir and levitate liquid metals. There is the terrestrial magnetic field which is maintained by fluid motion in the earth's core, the solar magnetic field, which generates sunspots and solar flares, and the galactic field which influences the formation of stars. This is an introductory text on magnetohydrodynamics (MHD) - the study of the interaction of magnetic fields and conducting fluids. This book is intended to serve as an introductory text for advanced undergraduates and postgraduate students in physics, applied mathematics and engineering. The material in the text is heavily weighted towards incompressible flows and to terrestrial (as distinct from astrophysical) applications. The final sections of the text also contain an outline of the latest advances in the metallurgical applications of MHD and so are relevant to professional researchers in applied mathematics, engineering and metallurgy.
Pattern Formation and Dynamics in Nonequilibrium Systems
Authors: Cross Michael , Greenside Henry
Published: March 2010

Many exciting frontiers of science and engineering require understanding the spatiotemporal properties of sustained nonequilibrium systems such as fluids, plasmas, reacting and diffusing chemicals, crystals solidifying from a melt, heart muscle, and networks of excitable neurons in brains. This introductory textbook for graduate students in biology, chemistry, engineering, mathematics, and physics provides a systematic account of the basic science common to these diverse areas. This book provides a careful pedagogical motivation of key concepts, discusses why diverse nonequilibrium systems often show similar patterns and dynamics, and gives a balanced discussion of the role of experiments, simulation, and analytics. It contains numerous worked examples and over 150 exercises. This book will also interest scientists who want to learn about the experiments, simulations, and theory that explain how complex patterns form in sustained nonequilibrium systems.
'Religion' and the Religions in the English Enlightenment
Authors: Harrison Peter
Published: March 2010

This study examines the changes which took place in the understanding of 'religion' and 'the religions' during the Enlightenment in England, the period when the decisive break with Patristic, Medieval and Renaissance notions of religion occurred. Dr Harrison's view is that the principles of the English Enlightenment not only made a special contribution to our modern understanding of what religion is, but they pioneered, in addition, the 'scientific', or non-religious approach, to religious phenomena. During this period a crisis of authority in the Church necessitated a rational enquiry into the various forms of Christianity, and in addition, into the claims of all religions. This led to a concept of 'religion' (based on 'natural' theology) which could link together the apparently disparate religious beliefs and practices found in the empirical religions.
Theory of International Trade
Authors: Dixit Avinash , Norman Victor
Published: March 2010

This book expounds trade theory emphasizing that a trading equilibrium is general rather than partial, and is often best modelled using dual or envelope functions. This yields a compact treatment of standard theory, clarifies some errors and confusions, and produces some new departures. In particular, the book (i) gives unified treatments of comparative statics and welfare, (ii) sheds new light on the factor-price equalization issue, (iii) treats the modern specific-factor model in parallel with the usual Heckscher-Ohlin one, (iv) analyses the balance of payments in general equilibrium with flexible and fixed prices, (v) studies imperfect competition and intra-industry trade.
The Challenge of Child Labour in International Law
Authors: Humbert Franziska
Published: March 2010

Child labour remains a widespread problem around the world. Over 200 million children can be regarded as child labourers, and about 10 million children are involved in producing either agricultural or manufactured products for export. Franziska Humbert explores the status of child labour in international law. Offering a wide-ranging analysis of the problem, she explores the various UN and ILO instruments and reveals the weaknesses of the current frameworks installed by these bodies to protect children from economic exploitation. After assessing to what extent trade measures such as conditionalities, labelling and trade restrictions and promotional activities can reduce child labour, she suggests an alternative legal framework which takes into account the needs of children.
Task-Based Language Teaching
Authors: Nunan David
Published: March 2010

The field of task-based language teaching has developed considerably since the publication of Designing Tasks for the Communicative Classroom (Nunan, 1989), a book which helped to set the research agenda in teaching methodology for the following decade. While Designing Tasks underpins this new title, the material has been thoroughly updated and includes four completely new chapters. Task-Based Language Teaching offers a comprehensive and up-to-date appraisal of the field.
American Literature and the Free Market, 1945–2000
Authors: Clune Michael W.
Published: March 2010

The years after World War Two have seen a widespread fascination with the free market. In this book, Michael W. Clune considers this fascination in postwar literature. In the fictional worlds created by works ranging from Frank O'Hara's poetry to nineties gangster rap, the market is transformed, offering an alternative form of life, distinct from both the social visions of the left and the individualist ethos of the right. These ideas also provide an unsettling example of how art takes on social power by offering an escape from society. American Literature and the Free Market presents a new perspective on a number of wide ranging works for readers of American post-war literature.
SUPERADDITIVITY OF SOME FUNCTIONALS ASSOCIATED WITH JENSEN’S INEQUALITY FOR CONVEX FUNCTIONS ON LINEAR SPACES WITH APPLICATIONS
Authors: DRAGOMIR S. S.
Published: March 2010

Some new results related to Jensen’s celebrated inequality for convex functions defined on convex sets in linear spaces are given. Applications for norm inequalities in normed linear spaces andf-divergences in information theory are provided as well.
ON PRIME-LIKE RADICALS
Authors: TUMURBAT S. , FRANCE-JACKSON H.
Published: March 2010

A radical γ is prime-like if, for every prime ring A, the polynomial ring A[x] is γ-semisimple. In this paper, we study properties of prime-like radicals. In particular, we give necessary and sufficient conditions for a radical γ containing the prime radical β to be prime-like. This allows us to easily find distinct special radicals that coincide on simple rings and on polynomial rings, which answers a question put by Ferrero. It also allows us to reformulate a long-standing open problem of Gardner in terms of prime-like radicals.
QUADRATIC CURVATURE ENERGIES IN THE 2-SPHERE
Authors: ARROYO JOSU , GARAY ÓSCAR J. , MENCÍA JOSE
Published: March 2010

The classical variational analysis of curvature energy functionals, acting on spaces of curves of a Riemannian manifold, is extremely complicated, and the procedure usually can not be completely developed under such a degree of generality. Sometimes this difficulty may be overcome by focusing on specific actions in real space forms. In this note, we restrict ourselves to quadratic Lagrangian energies acting on the space of closed curves of the 2-sphere. We solve the Euler–Lagrange equation and show that there exists a two-parameter family of closed critical curves. We also discuss the stability of the circular critical points. Since, even for this class of energies, the complete variational analysis is quite involved, we use instead a numerical approach to provide a useful method of visualization of relevant aspects concerning uniqueness, stability and explicit representation of the closed critical curves.
Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort
Authors: Leffelaar Evelien R. , Vrijkotte Tanja G. M. , van Eijsden Manon
Published: March 2010

Low vitamin D levels during pregnancy may account for reduced fetal growth and for altered neonatal development. The present study explored the association between maternal vitamin D status measured early in pregnancy and birth weight, prevalence of small-for-gestational-age (SGA) infants and postnatal growth (weight and length), as well as the potential role of vitamin D status in explaining ethnic disparities in these outcomes. Data were derived from a large multi-ethnic cohort in The Netherlands (Amsterdam Born Children and their Development (ABCD) cohort), and included 3730 women with live-born singleton term deliveries. Maternal serum vitamin D was measured during early pregnancy (median 13 weeks, interquartile range: 12–14), and was labelled ‘deficient’ ( ≤ 29·9 nmol/l), ‘insufficient’ (30–49·9 nmol/l) or ‘adequate’ ( ≥ 50 nmol/l). Six ethnic groups were distinguished: Dutch, Surinamese, Turkish, Moroccan, other non-Western and other Western. Associations with neonatal outcomes were analysed using multivariate regression analyses. Results showed that compared with women with adequate vitamin D levels, women with deficient vitamin D levels had infants with lower birth weights ( − 114·4 g, 95 % CI − 151·2, − 77·6) and a higher risk of SGA (OR 2·4, 95 % CI 1·9, 3·2). Neonates born to mothers with a deficient vitamin D status showed accelerated growth in weight and length during the first year of life. Although a deficient vitamin D status influenced birth weight, SGA risk and neonatal growth, it played a limited role in explaining ethnic differences. Although vitamin D supplementation might be beneficial to those at risk of a deficient vitamin D status, more research is needed before a nationwide policy on the subject can be justified.
Others No More: The Changing Representation of Non-Han Peoples in Chinese History Textbooks, 1951–2003
Authors: Baranovitch Nimrod
Published: March 2010

This article analyzes the changes in the representation of non-Han peoples in textbooks of premodern Chinese history published in China since the establishment of the People's Republic. Whereas in the early 1950s, these peoples were treated as non-Chinese others and were even referred to as “foreigners,” by the beginning of the twenty-first century, they were totally incorporated into the Chinese historical self through a new narrative claiming that they had always been Chinese. Simultaneously, the textbooks exhibit a clear shift from a Han-exclusivist vision of Chinese history to a more inclusive and multi-ethnic one. Based on an analysis of the content, language, and organization of textbooks and other related materials, the article proposes that although the incorporation of non-Han peoples into the Chinese historical subject was gradual, this process accelerated dramatically as a result of a planned reform launched in the late 1970s and early 1980s. The article explains the reasons for the reform and its timing, and examines its implications for the Chinese nation-state and China's ethnic minorities.
Atypical presentations of malignant otitis externa
Authors: Vourexakis Z , Kos M-I , Guyot J-P
Published: March 2010

Introduction:

Malignant otitis externa is a life-threatening infection of the skull base. Its presentation is not always typical.

Case reports:

We report three cases of malignant otitis externa which illustrate the diversity of its clinical manifestations and the difficulties in its diagnosis.

Discussion:

The perception of malignant otitis externa as an infection caused byPseudomonas aeruginosain diabetic patients is not always correct. The adoption of diagnostic criteria could be helpful in identifying atypical cases.
Alcohol use among older adults
Authors: St John Philip D , Snow Wanda M , Tyas Suzanne L
Published: March 2010

Alcohol use is common in older adults and is associated with numerous health and social problems. Recent evidence suggests that in addition to level of alcohol consumption, drinking pattern may also be important. Moderate alcohol intake may confer some cardiac benefits, while heavy episodic drinking seems particularly problematic. Detecting alcohol misuse in older adults is difficult since clinical acumen is often poor, screening questionnaires have serious limitations and laboratory tests are not diagnostic. Brief alcohol interventions to reduce alcohol consumption appear useful in younger populations, but are less studied in older adults. While there is increasing research into the issue of alcohol use among older adults, clinicians and policy-makers must rely on limited evidence when making clinical decisions.
Pneumonia and influenza – specific considerations in care homes
Authors: Gordon Adam , Ewan Victoria
Published: March 2010

This review provides an update on current evidence surrounding epidemiology, treatment and prevention of lower respiratory tract infection, with special reference to pneumonia and influenza, in care home residents. The care home sector is growing and provides a unique ecological niche for infections, housing frail older people with multiple co-morbidities and frequent contact with healthcare services. There are therefore considerations in the epidemiology and management of these conditions that are specific to care homes. Opportunities for prevention, in the form of vaccination strategies and improving oral hygiene, may reduce the burden of these diseases in the future. Work is needed to research these infections specifically in the care home setting, and this article highlights current gaps in our knowledge.
Characterization of dormancy behaviour in seeds of the model legumeMedicago truncatula
Authors: Bolingue William , Ly Vu Benoit , Leprince Olivier , Buitink Julia
Published: March 2010

Seeds ofMedicago truncatula, a genomic model species for legumes, exhibit physiological and physical dormancy. Here, the factors influencing the germination behaviour of freshly harvested and stored seeds were investigated using several genotypes. Hardseededness is promoted when mature seeds are equilibrated at relative humidities (RH) below 75%. The release of physical dormancy during imbibition was dependent on the initial water content/RH that the seeds were dried to: the drier the seeds, the longer the imbibition time needed to break physical dormancy. The kinetics of physical dormancy release was slower than that of physiological dormancy, making it possible to uncouple both phenomena. Freshly harvested embryos without seed coverings germinated at the same speed as afterripened seeds. The depth of dormancy varied between differentM. truncatulagenotypes, from more to less dormant: DZA315.16>A17 (Jemalong)>R108>DZA45.5. This difference was eliminated by removing the endosperm. Collectively, these observations indicate that the endosperm is likely the main factor in the reduced germination of freshly harvested seeds. White light decreased germination speed of dormant seeds whereas it had no effect on non-dormant seeds. Recently harvested seeds were most dormant at temperatures above 17°C, whereas afterripened seeds germinated over a wider range of temperature. Fluridone could efficiently break dormancy, reinforcing the role of abscisic acid (ABA) synthesis. However, dormancy was not affected by gibberellic acid (100 μM GA3) or nitrate. The particular dormancy features unravelled here forM. truncatula, combined with the available genomic resources, make it a new, useful model for genetic and molecular studies which can complement those developed for Arabidopsis.
Inverting geodetic time series with a principal component analysis‐based inversion method
Authors: Kositsky A. P. , Avouac J.‐P.
Published: March 2010

The Global Positioning System (GPS) system now makes it possible to monitor deformation of the Earth's surface along plate boundaries with unprecedented accuracy. In theory, the spatiotemporal evolution of slip on the plate boundary at depth, associated with either seismic or aseismic slip, can be inferred from these measurements through some inversion procedure based on the theory of dislocations in an elastic half‐space. We describe and test a principal component analysis‐based inversion method (PCAIM), an inversion strategy that relies on principal component analysis of the surface displacement time series. We prove that the fault slip history can be recovered from the inversion of each principal component. Because PCAIM does not require externally imposed temporal filtering, it can deal with any kind of time variation of fault slip. We test the approach by applying the technique to synthetic geodetic time series to show that a complicated slip history combining coseismic, postseismic, and nonstationary interseismic slip can be retrieved from this approach. PCAIM produces slip models comparable to those obtained from standard inversion techniques with less computational complexity. We also compare an afterslip model derived from the PCAIM inversion of postseismic displacements following the 2005 8.6 Nias earthquake with another solution obtained from the extended network inversion filter (ENIF). We introduce several extensions of the algorithm to allow statistically rigorous integration of multiple data sources (e.g., both GPS and interferometric synthetic aperture radar time series) over multiple timescales. PCAIM can be generalized to any linear inversion algorithm.
Development of a bimodal structure in ocean wave spectra
Authors: Toffoli A. , Onorato M. , Bitner‐Gregersen E. M. , Monbaliu J.
Published: March 2010

Traditionally, the directional distribution of ocean waves has been regarded as unimodal, with energy concentrated mainly on the wind direction. However, numerical experiments and field measurements have already demonstrated that the energy of short waves tends to be accumulated along two off‐wind directions, generating a bimodal directional distribution. Here, numerical simulations of the potential Euler equations are used to investigate the temporal evolution of initially unimodal directional wave spectra. Because this approach does not include external forcing such as wind and breaking dissipation, spectral changes are only driven by nonlinear interactions. The simulations show that the wave energy spreads outward from the spectral peak, following two characteristic directions. As a result, the directional distribution develops a bimodal form as the wavefield evolves. Although bimodal properties are more pronounced in the high wave number part of the spectrum, in agreement with previous field measurements, the simulations also show that directional bimodality characterizes the spectral peak.
Dam safety effects due to human alteration of extreme precipitation
Authors: Hossain Faisal , Jeyachandran Indumathi , Pielke Roger
Published: March 2010

Very little is known about the vulnerability of dams and reservoirs to man‐made alteration of extreme precipitation and floods as we step into the 21st century. This is because conventional dam and reservoir design over the last century has been “one‐way” with no acknowledgment of the possible feedback mechanisms affecting the regional water cycle. Although the notion that an impoundment could be built to increase rainfall was suggested more than 60 years ago, dam design protocol in civil engineering continues to assume as “static” the statistical parameters of a low exceedance probability precipitation event during the lifespan of the dam. It is time for us to change our perceptions and embrace a hydrometeorological approach to dam design and operations.
Bruce T. Tsurutani Receives 2009 John Adam Fleming Medal
Authors: Kozyra Janet U. , Tsurutani Bruce T.
Published: March 2010

Bruce T. Tsurutani was awarded the 2009 John Adam Fleming Medal at the AGU Fall Meeting Honors Ceremony, held on 16 December 2009 in San Francisco, Calif. The medal is for “original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, space physics, and related sciences.”
The basis of morality
Authors: Hunter Philip
Published: March 2010

The neurological explanation and evolutionary development of our capacity for moral reasoning remain elusive. New research suggests that it is based on an awareness and that various animals have also evolved this very human approach to the world.
Pandemics: is hoping for the best enough?
Authors: Osterhaus Albert D M E
Published: March 2010

Albert Osterhaus reflects on the reasons for the increase in emerging pandemics and how we are coping with these situations. Although we might risk over‐reacting, better safe than sorry is still the most reasonable policy.
Overcoming Barriers to Climate Change Adaptation—A Question of Multilevel Governance?
Authors: Amundsen Helene , Berglund Frode , Westskog Hege
Published: March 2010

This paper analyses the results from two surveys which were sent to all Norwegian municipalities in 2007 and gives an overview of adaptation measures undertaken by local governments. Our analyses show that municipalities have more often invested in measures related to extreme precipitation and flooding than in measures for securing buildings and infrastructure against climate change. One key factor explaining their efforts is whether they have experienced extreme events. Hence adaptation efforts are mainly reactive. With a changing climate comes a greater demand for proactive adaptation processes, as well as knowledge of how adaptation policies and measures could be implemented successfully. This paper emphasises the importance of enhancing institutional capacity in order to address the challenges of climate change adaptation at the municipal level; and asserts that a multilevel governance framework is a way of advancing proactive adaptation and overcoming the identified barriers to adaptation.
My Space: Governing Individuals' Carbon Emissions
Authors: Paterson Matthew , Stripple Johannes
Published: March 2010

This paper examines the recent growth in projects designed to enable individuals to ‘do their bit’ in the struggle to limit climate change. It discusses them in relation to a long-standing critique of trends towards individualisation amongst environmentalists. It suggests that this critique misses the complex way that subjects are produced by these practices and proposes to analyse subjectification in relation to climate change through the lens of governmentality. The paper then proceeds to examine five specific sorts of practice: carbon footprinting; carbon offsetting; carbon dieting; Carbon Reduction Action Groups; and Personal Carbon Allowances. By drawing on the concept of governmentality we show how contemporary forms of carbon government work through calculative practices that simultaneously totalise (aggregating social practices, overall greenhouse gas emissions) and individualise (producing reflexive subjects actively managing their greenhouse gas practices).
Geometric cues for directing the differentiation of mesenchymal stem cells
Authors: Kilian Kristopher A. , Bugarija Branimir , Lahn Bruce T. , Mrksich Milan
Published: March 2010

Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
Random cell movement promotes synchronization of the segmentation clock
Authors: Uriu Koichiro , Morishita Yoshihiro , Iwasa Yoh
Published: March 2010

In vertebrate somitogenesis, the expression of segmentation clock genes oscillates and the oscillation is synchronized over nearby cells. Both experimental and theoretical studies have shown that the synchronization among cells is realized by intercellular interaction via Delta–Notch signaling. However, the following questions emerge: (
i
) During somitogenesis, dynamic rearrangement of relative cell positions is observed in the posterior presomitic mesoderm. Can a synchronized state be stably sustained under random cell movement? (
ii
) Experimental studies have reported that the synchronization of cells can be recovered in about 10 or fewer oscillation cycles after the complete loss of synchrony. However, such a quick recovery of synchronization is not possible according to previous theoretical models. In this paper, we first show by numerical modeling that synchronized oscillation can be sustained under random cell movement. We also find that for initial perturbation, the synchronization of cells is recovered much faster and it is for a wider range of reaction parameters than the case without cell movement. When the posterior presomitic mesoderm is rectangular, faster synchronization is achieved if cells exchange their locations more with neighbors located along the longer side of the domain. Finally, we discuss that the enhancement of synchronization by random cell movement occurs in several different models for the oscillation of segmentation clock genes.
Atomically detailed simulation of the recovery stroke in myosin by Milestoning
Authors: Elber Ron , West Anthony
Published: March 2010

Myosin II is a molecular motor that converts chemical to mechanical energy and enables muscle operations. After a power stroke, a recovery transition completes the cycle and returns the molecular motor to its prestroke state. Atomically detailed simulations in the framework of the Milestoning theory are used to calculate kinetics and mechanisms of the recovery stroke. Milestoning divides the process into transitions between hyper-surfaces (Milestones) along a reaction coordinate. Decorrelation of dynamics between sequential Milestones is assumed, which speeds up the atomically detailed simulations by a factor of millions. Two hundred trajectories of myosin with explicit water solvation are used to sample transitions between sequential pairs of Milestones. Collective motions of hundreds of atoms are described at atomic resolution and at the millisecond time scale. The experimentally measured transition time of about a millisecond is in good agreement with the computed time. The simulations support a sequential mechanism. In the first step the P-loop and switch 2 close on the ATP and in the second step the mechanical relaxation is induced via the relay and the SH1 helices. We propose that the entropy of switch 2 helps to drive the power stroke. Secondary structure elements are progressing through a small number of discrete states in a network of activated transitions and are assisted by side chain flips between rotameric states. The few-state sequential mechanism is likely to enhance the efficiency of the relaxation reducing the probability of off-pathway intermediates.
LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy
Authors: Liu Chia-Chen , Prior Julie , Piwnica-Worms David , Bu Guojun
Published: March 2010

The Wnt/β-catenin signaling pathway is activated in breast cancer, a leading cause of cancer mortality in women. Because mutations in the key intracellular components of this pathway are rare, identifying the molecular mechanisms of aberrant Wnt activation in breast cancer is critical for development of pathway-targeted therapy. Here, we show that expression of the Wnt signaling coreceptor LRP6 is up-regulated in a subpopulation of human breast cancers. LRP6 silencing in breast cancer cells reduces Wnt signaling, cell proliferation, and in vivo tumor growth. In vivo administration of an LRP6 antagonist, Mesd, markedly suppressed growth of MMTV-Wnt1 tumors without causing undesirable side effects. These results demonstrate that Wnt activation at the cell surface contributes to breast cancer tumorigenesis. Together, our studies highlight LRP6 as a potential therapeutic target in breast cancer, and introduce Mesd as a promising antitumor agent for treating breast cancer subtypes with Wnt activation at the cell surface.
Optimal reward harvesting in complex perceptual environments
Authors: Navalpakkam Vidhya , Koch Christof , Rangel Antonio , Perona Pietro
Published: March 2010

The ability to choose rapidly among multiple targets embedded in a complex perceptual environment is key to survival. Targets may differ in their reward value as well as in their low-level perceptual properties (e.g., visual saliency). Previous studies investigated separately the impact of either value or saliency on choice; thus, it is not known how the brain combines these two variables during decision making. We addressed this question with three experiments in which human subjects attempted to maximize their monetary earnings by rapidly choosing items from a brief display. Each display contained several worthless items (distractors) as well as two targets, whose value and saliency were varied systematically. We compared the behavioral data with the predictions of three computational models assuming that (
i
) subjects seek the most valuable item in the display, (
ii
) subjects seek the most easily detectable item, and (
iii
) subjects behave as an ideal Bayesian observer who combines both factors to maximize the expected reward within each trial. Regardless of the type of motor response used to express the choices, we find that decisions are influenced by both value and feature-contrast in a way that is consistent with the ideal Bayesian observer, even when the targets’ feature-contrast is varied unpredictably between trials. This suggests that individuals are able to harvest rewards optimally and dynamically under time pressure while seeking multiple targets embedded in perceptual clutter.
Polygenic and directional regulatory evolution across pathways inSaccharomyces
Authors: Bullard James H. , Mostovoy Yulia , Dudoit Sandrine , Brem Rachel B.
Published: March 2010

The search to understand how genomes innovate in response to selection dominates the field of evolutionary biology. Powerful molecular evolution approaches have been developed to test individual loci for signatures of selection. In many cases, however, an organism's response to changes in selective pressure may be mediated by multiple genes, whose products function together in a cellular process or pathway. Here we assess the prevalence of polygenic evolution in pathways in the yeastsSaccharomyces cerevisiaeandS. bayanus. We first established short-read sequencing methods to detectcis-regulatory variation in a diploid hybrid between the species. We then tested for the scenario in which selective pressure in one species to increase or decrease the activity of a pathway has driven the accumulation ofcis-regulatory variants that act in the same direction on gene expression. Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution. In parallel, we also used population genomic sequencing data to compare protein andcis-regulatory variation within and between species. We identified pathways with evidence for divergence withinS. cerevisiae, and we detected signatures of positive selection betweenS. cerevisiaeandS. bayanus.Our results point to polygenic, pathway-level change as a common evolutionary mechanism among yeasts. We suggest that pathway analyses, including our test for directional regulatory evolution, will prove to be a relevant and powerful strategy in many evolutionary genomic applications.
A Howiesons Poort tradition of engraving ostrich eggshell containers dated to 60,000 years ago at Diepkloof Rock Shelter, South Africa
Authors: Texier Pierre-Jean , Porraz Guillaume , Parkington John , Rigaud Jean-Philippe , Poggenpoel Cedric , Miller Christopher , Tribolo Chantal , Cartwright Caroline , Coudenneau Aude , Klein Richard , Steele Teresa , Verna Christine
Published: March 2010

Ongoing debates about the emergence of modern human behavior, however defined, regularly incorporate observations from the later part of the southern African Middle Stone Age and emphasize the early appearance of artifacts thought to reflect symbolic practice. Here we report a large sample of 270 fragments of intentionally marked ostrich eggshell from the Howiesons Poort at Diepkloof Rock Shelter, Western Cape, South Africa. Dating from ≈60,000 years ago, these pieces attest to an engraving tradition that is the earliest reliable evidence of what is a widespread modern practice. These abstract linear depictions were made on functional items (eggshell containers), which were curated and involved in daily hunter-gatherer life. The standardized production of repetitive patterns, including a hatched band motif, suggests a system of symbolic representation in which collective identities and individual expressions are clearly communicated, suggesting social, cultural, and cognitive underpinnings that overlap with those of modern people.
Loss of high-frequency glucose-induced Ca
2+
oscillations in pancreatic islets correlates with impaired glucose tolerance in

Trpm5
−/−

mice
Authors: Colsoul Barbara , Schraenen Anica , Lemaire Katleen , Quintens Roel , Van Lommel Leentje , Segal Andrei , Owsianik Grzegorz , Talavera Karel , Voets Thomas , Margolskee Robert F. , Kokrashvili Zaza , Gilon Patrick , Nilius Bernd , Schuit Frans C. , Vennekens Rudi
Published: March 2010

Glucose homeostasis is critically dependent on insulin release from pancreatic β-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V
m
) and the cytosolic calcium level ([Ca
2+
]
cyt
). We propose that TRPM5, a Ca
2+
-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca
2+
-activated nonselective cation current with TRPM5-like properties is significantly reduced in
Trpm
5
−/−
cells. Ca
2+
-imaging and electrophysiological analysis show that glucose-induced oscillations of V
m
and [Ca
2+
]
cyt
have on average a reduced frequency in

Trpm5
−/−

islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from
Trpm5
−/−
pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in
Trpm5
−/−
mice.
Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes
Authors: Spreu Jessica , Kuttruff Sabrina , Stejfova Veronika , Dennehy Kevin M. , Schittek Birgit , Steinle Alexander
Published: March 2010

Many well-known immune-related C-type lectin-like receptors (CTLRs) such as NKG2D, CD69, and the Ly49 receptors are encoded in the natural killer gene complex (NKC). Recently, we characterized the orphan NKC geneCLEC2Aencoding for KACL, a further member of the human CLEC2 family of CTLRs. In contrast to the other CLEC2 family members AICL, CD69, and LLT1, KACL expression is mostly restricted to skin. Here we show that KACL is a non–disulfide-linked homodimeric surface receptor and stimulates cytotoxicity by human NK92MI cells. We identified the corresponding activating receptor on NK92MI cells that is encoded adjacently to theCLEC2Alocus and binds KACL with high affinity. This CTLR, termed NKp65, stimulates NK cytotoxicity and release of proinflammatory cytokines upon engagement of cell-bound KACL. NKp65, a distant relative of the human activating NK receptor NKp80, possesses an amino-terminal hemITAM that is required for NKp65-mediated cytotoxicity. Finally, we show that KACL expression is mainly restricted to keratinocytes. Freshly isolated keratinocytes express KACL and are capable of stimulating NKp65-expressing cells in a KACL-dependent manner. Thus, we report a unique NKC-encoded receptor-ligand system that may fulfill a dedicated function in the immunobiology of human skin.
A link between the assembly of flagella and lipooligosaccharide of the Gram-negative bacterium
Campylobacter jejuni
Authors: Cullen Thomas W. , Trent M. Stephen
Published: March 2010

Campylobacter jejuni
is the leading cause of acute bacterial diarrhea worldwide and is implicated in development of Guillain-Barré syndrome. Two major surface features, the outer membrane lipooligosaccharide and flagella, are highly variable and are often targets for modification. Presumably, these modifications provide a competitive advantage to the bacterium. In this work, we identify a gene encoding a phosphoethanolamine (pEtN) transferase (Cj0256) that serves a dual role in modifying not only the lipooligosaccharide lipid anchor lipid A with pEtN, but also the flagellar rod protein FlgG. Generation of a mutant in
C. jejuni
81–176 by interruption of
cj0256
resulted in the absence of pEtN modifications on lipid A as well as FlgG. The
cj0256
mutant showed a 20-fold increase in sensitivity to the cationic antimicrobial peptide, polymyxin B, as well as a decrease in motility. Transmission EM of the
cj0256
mutant revealed a population (approximately 95%) lacking flagella, indicating that, without pEtN modification of FlgG, flagella production is hindered. Most intriguing, this research identifies a pEtN transferase showing preference for two periplasmic substrates linking membrane biogenesis and flagellar assembly. Cj0256 is a member of a large family of mostly uncharacterized proteins that may play a larger role in the decoration of bacterial surface structures.
Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing
Authors: Wu Jia Qian , Habegger Lukas , Noisa Parinya , Szekely Anna , Qiu Caihong , Hutchison Stephen , Raha Debasish , Egholm Michael , Lin Haifan , Weissman Sherman , Cui Wei , Gerstein Mark , Snyder Michael
Published: March 2010

To examine the fundamental mechanisms governing neural differentiation, we analyzed the transcriptome changes that occur during the differentiation of hESCs into the neural lineage. Undifferentiated hESCs as well as cells at three stages of early neural differentiation—N1 (early initiation), N2 (neural progenitor), and N3 (early glial-like)—were analyzed using a combination of single read, paired-end read, and long read RNA sequencing. The results revealed enormous complexity in gene transcription and splicing dynamics during neural cell differentiation. We found previously unannotated transcripts and spliced isoforms specific for each stage of differentiation. Interestingly, splicing isoform diversity is highest in undifferentiated hESCs and decreases upon differentiation, a phenomenon we call
isoform specialization
. During neural differentiation, we observed differential expression of many types of genes, including those involved in key signaling pathways, and a large number of extracellular receptors exhibit stage-specific regulation. These results provide a valuable resource for studying neural differentiation and reveal insights into the mechanisms underlying in vitro neural differentiation of hESCs, such as neural fate specification, neural progenitor cell identity maintenance, and the transition from a predominantly neuronal state into one with increased gliogenic potential.
Seromic profiling of ovarian and pancreatic cancer
Authors: Gnjatic Sacha , Ritter Erika , Büchler Markus W. , Giese Nathalia A. , Brors Benedikt , Frei Claudia , Murray Anne , Halama Niels , Zörnig Inka , Chen Yao-Tseng , Andrews Christopher , Ritter Gerd , Old Lloyd J. , Odunsi Kunle , Jäger Dirk
Published: March 2010

Autoantibodies, a hallmark of both autoimmunity and cancer, represent an easily accessible surrogate for measuring adaptive immune responses to cancer. Sera can now be assayed for reactivity against thousands of proteins using microarrays, but there is no agreed-upon standard to analyze results. We developed a set of tailored quality control and normalization procedures based on ELISA validation to allow patient comparisons and determination of individual cutoffs for specificity and sensitivity. Sera from 60 patients with pancreatic cancer, 51 patients with ovarian cancer, and 53 age-matched healthy donors were used to assess the binding of IgG antibodies against a panel of >8000 human antigens using protein microarrays and fluorescence detection. The resulting data interpretation led to the definition and ranking of proteins with preferred recognition by the sera from cancer patients in comparison with healthy donors, both by frequency and strength of signal. We found that 202 proteins were preferentially immunogenic in ovarian cancer sera compared to 29 in pancreatic cancer, with few overlaps. Correlates of autoantibody signatures with known tumor expression of corresponding antigens, functional pathways, clinical stage, and outcome were examined. Serological analysis of arrays displaying the complete human proteome (seromics) represents a new era in cancer immunology, opening the way to defining the repertoire of the humoral immune response to cancer.
A ratchet mechanism for amplification in low-frequency mammalian hearing
Authors: Reichenbach Tobias , Hudspeth A. J.
Published: March 2010

The sensitivity and frequency selectivity of hearing result from tuned amplification by an active process in the mechanoreceptive hair cells. In most vertebrates, the active process stems from the active motility of hair bundles. The mammalian cochlea exhibits an additional form of mechanical activity termed electromotility: its outer hair cells (OHCs) change length upon electrical stimulation. The relative contributions of these two mechanisms to the active process in the mammalian inner ear is the subject of intense current debate. Here, we show that active hair-bundle motility and electromotility can together implement an efficient mechanism for amplification that functions like a ratchet: Sound-evoked forces, acting on the basilar membrane, are transmitted to the hair bundles, whereas electromotility decouples active hair-bundle forces from the basilar membrane. This unidirectional coupling can extend the hearing range well below the resonant frequency of the basilar membrane. It thereby provides a concept for low-frequency hearing that accounts for a variety of unexplained experimental observations from the cochlear apex, including the shape and phase behavior of apical tuning curves, their lack of significant nonlinearities, and the shape changes of threshold tuning curves of auditory-nerve fibers along the cochlea. The ratchet mechanism constitutes a general design principle for implementing mechanical amplification in engineering applications.
Evolution of species-specific promoter-associated mechanisms for protecting chromosome ends by Drosophila
Het
-
A
telomeric transposons
Authors: Traverse Karen L. , George Janet A. , DeBaryshe P. G. , Pardue Mary-Lou
Published: March 2010

The non-LTR retrotransposons forming Drosophila telomeres constitute a robust mechanism for telomere maintenance, one which has persisted since before separation of the extant Drosophila species. These elements in
D. melanogaster
differ from nontelomeric retrotransposons in ways that give insight into general telomere biology. Here, we analyze telomere-specific retrotransposons from
D. virilis
, separated from
D. melanogaster
by 40 to 60 million years, to evaluate the evolutionary divergence of their telomeric traits. The telomeric retrotransposon
HeT-A
from
D. melanogaster
has an unusual promoter near its 3′ terminus that drives not the element in which it resides, but the adjacent downstream element in a head-to-tail array. An obvious benefit of this promoter is that it adds nonessential sequence to the 5′ end of each transcript, which is reverse transcribed and added to the chromosome. Because the 5′ end of each newly transposed element forms the end of the chromosome until another element transposes onto it, this nonessential sequence can buffer erosion of sequence essential for
HeT-A
. Surprisingly, we have now found that
HeT-A
in
D. virilis
has a promoter typical of non-LTR retrotransposons. This promoter adds no buffering sequence; nevertheless, the complete 5′ end of the element persists in telomere arrays, necessitating a more precise processing of the extreme end of the telomere in
D. virilis
.