bluuebunny/crossref_metadata_2025 huggingface dataset:
Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging
Authors: Doi Hiroshi , Shiomi Hiroya , Masai Norihisa , Tatsumi Daisaku , Igura Takumi , Imai Yasuharu , Oh Ryoong-Jin
Published: March 2016

The purpose of the present study was to investigate the threshold dose for focal liver damage after stereotactic body radiation therapy (SBRT) in cirrhotic and normal livers using magnetic resonance imaging (MRI). A total of 64 patients who underwent SBRT for liver tumors, including 54 cirrhotic patients with hepatocellular carcinoma (HCC) and 10 non-cirrhotic patients with liver metastases, were analyzed. MRI was performed 3−6 months after SBRT, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1-weighted sequences. All MRI datasets were merged with 3D dosimetry data. All dose distributions were corrected to the biologically effective dose using the linear–quadratic model with an assumed α/β ratio of 2 Gy. The development of liver dysfunction was validly correlated with isodose distribution. The median biologically effective dose (BED 2 ) that provoked liver dysfunction was 57.3 (30.0−227.9) and 114.0 (70.4−244.9) Gy in cirrhotic and normal livers, respectively ( P = 0.0002). The BED 2 associated with a >5% risk of liver dysfunction was 38.5 in cirrhotic livers and 70.4 Gy in normal livers. The threshold BED 2 for liver dysfunction was not significantly different between Child−Pugh A and B patients ( P = 0.0719). Moreover, the fractionation schedule was not significantly correlated with threshold BED 2 for liver dysfunction in the cirrhotic liver ( P = 0.1019). In the cirrhotic liver, fractionation regimen and Child−Pugh classification did not significantly influence the threshold BED 2 for focal liver damage after SBRT. We suggest that the threshold BED 2 for liver dysfunction after SBRT is 40 and 70 Gy in the cirrhotic and normal liver, respectively.
Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83–100 Gy in five fractions
Authors: Takeda Atsuya , Sanuki Naoko , Tsurugai Yuichiro , Oku Yohei , Aoki Yousuke
Published: March 2016

We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50–60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5–43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT.
Proteome and Protein Network Analyses of Memory T Cells Find Altered Translation and Cell Stress Signaling in Treated Human Immunodeficiency Virus Patients Exhibiting Poor CD4 Recovery
Authors: Azzam Sausan , Schlatzer Daniela , Maxwell Sean , Li Xiaolin , Bazdar Douglas , Chen Yanwen , Asaad Robert , Barnholtz-Sloan Jill , Chance Mark R. , Sieg Scott F.
Published: March 2016

Background.  Human immunodeficiency virus (HIV) patients who experience poor CD4 T-cell recovery despite viral suppression during antiretroviral therapy (ART) are known as immunological nonresponders. The molecular mechanism(s) underlying incomplete immune restoration during ART is not fully understood.

Methods.  Label-free quantitative proteomics on single-cell type central memory T cells were used to reveal relative protein abundance changes between nonresponder, responder (good CD4 recovery during ART), and healthy individuals. Proteome changes were analyzed by protein pathway and network analyses and verified by selected reaction monitoring mass spectrometry.

Results.  Proteomic analysis across groups detected 155 significant proteins from 1500 nonredundant proteins. Pathway and network analyses revealed dysregulation in mammalian target of rapamycin and protein translation-related proteins and decreases in stress response-related proteins for nonresponder subjects compared with responders and controls. Actin cytoskeleton signaling was increased for HIV responders and nonresponders alike.

Conclusions.  Memory T cells from immunologic nonresponders have increases in proteins related to motility and protein translation and decreases in proteins capable of responding to cellular stresses compared with responders and controls. The potential for T cells to manage stress and modulate metabolism may contribute to their capacity to reconstitute a lymphopenic host.
H. L. A. Hart, The Concept of Law
Authors: Kramer Matthew H.
Published: March 2016

H. L. A. Hartʼs The Concept of Law is, of course, primarily a work of legal philosophy. It is indeed the most influential work of legal philosophy in the English language (and perhaps in any language) published during the twentieth century. However, the immense importance of the book for philosophers of law should not prevent readers from discerning its importance for political and moral philosophers as well. Hartʼs insights into the nature of law and sovereignty are themselves of great significance for political philosophy, and the second half of The Concept of Law contains ruminations on justice and on the relationships between law and morality that deserve attention from anyone who aspires to think clearly about the problems of political philosophy.
Extraversion
Authors: Wilt Joshua , Revelle William
Published: March 2016

This chapter provides a review of extraversion, defined as a dimension of personality reflecting individual differences in the tendencies to experience and exhibit positive affect, assertive behavior, decisive thinking, and desires for social attention. Extraversion is one of five basic tendencies in the Five Factor Model (FFM) of personality. In the FFM, basic tendencies are conceptualized as including the following characteristics. They are organized hierarchically, based in biology, develop over time according to intrinsic maturation principles, are manifested in characteristic adaptations (i.e., are expressed in affective, behavioral, and cognitive tendencies), influence one’s objective biography, are reflected in the self-concept, and have both adaptive and maladaptive variants. This chapter is organized around the theory and research on extraversion relevant to each of the aforementioned characteristics.
Agreeableness and the Five Factor Model
Authors: Graziano William G. , M. Tobin Renée
Published: March 2016

Agreeableness is a summary label for individual differences in the motivation to maintain positive relations with others. Agreeableness is one of the major dimensions in the Big Five structural model of personality. It is also a major domain in the Five Factor Model of personality. This chapter provides an overview of the considerable body of research concerning the conceptualization, assessment, and etiology of Agreeableness with a focus on its six facets. It concludes with a discussion of alternative theoretical explanations for Agreeableness. In particular, an opponent process model that involves two competing motive systems is applied to the processes underlying Agreeableness.
Health Psychology
Authors: Kern Margaret L. , Friedman Howard S.
Published: March 2016

As research on personality and health has moved to developing multitrait, multioutcome models, the five factor approach has shown excellent utility for understanding health, including physical and mental health, longevity, cognitive function, social competence, and productivity. Drawing on a growing arsenal of advanced statistical techniques, studies are testing complex models to explain how personality influences health. Health behaviors, social situations, physiological changes, and various indirect and moderating factors are important pathways connecting personality and health, and reciprocally influence one another. Future personality research will benefit from interdisciplinary approaches, including integrative data analyses of archival data, big data analyses, neuroscientific approaches, and lifespan epidemiology. Bringing together different types of data, innovative methods, and well-specified theories offers the potential to understand the personality–health model in ways never before imagined. Identifying pathways and key factors in turn will inform effective intervention to help more people live healthier, more productive lives.
Information Retrieval
Authors: Mei Qiaozhu , Radev Dragomir R.
Published: March 2016

This chapter is a basic introduction to text information retrieval. Information Retrieval (IR) refers to the activities of obtaining information resources (usually in the form of textual documents) from a much larger collection, which are relevant to an information need of the user (usually expressed as a query). Practical instances of an IR system include digital libraries and Web search engines. This chapter presents the typical architecture of an IR system, an overview of the methods corresponding to the design and the implementation of each major component of an information retrieval system, a discussion of evaluation methods for an IR system, and finally a summary of recent developments and research trends in the field of information retrieval.
The Word
Authors: Puff Helmut
Published: March 2016

This chapter argues that, contrary to widespread notions about the Reformation as a period of the Word, the words the Reformers uttered should be considered in their social, cultural, and performative contexts. An analysis of a Protestant church interior, Luther’s Bible translation, and an exploration of the preached Word in Reformation Europe as well as an exploration of the differences within the pro-Reform faction are marshalled to illustrate that what was strikingly novel about the religious communities in this time period was not so much the hegemony of Holy Writ but the ensemble of textual and other media confessional churches instituted to bring communities into a novel age, infused with and inspired by the Word.
The Bohemian Reformations
Authors: Louthan Howard
Published: March 2016

The article examines religious changes in Bohemia and Moravia from the age of Emperor Charles IV (1346–1378) through the first half of the seventeenth century. It begins by considering the vibrant ecclesiastical landscape in the generation before Hus. After reviewing the tumultuous events of the Hussite era, it evaluates both the radical and more conservative legacy of this movement with the development of the Utraquist Church and the Unity of Brethren. Entering the sixteenth century, the article analyzes the impact of Luther and Calvin on the Bohemian churches, the dynamics of confessional cooperation and conflict. The essay closes with an investigation of the early seventeenth century, events leading to the outbreak of the Thirty Years War, the re-Catholization of the region, the exile generation of John Comenius, and the survival of Protestant enclaves within the kingdom.
Print Workshops and Markets
Authors: Pettegree Andrew
Published: March 2016

This paper considers the impact of the Reformation on the book culture of Europe, as it had developed in the seventy years since the invention of printing. The technical problems of printing with moveable type had been resolved relatively swiftly; the most testing challenge was to develop an infrastructure of distribution and sales. The result was a consolidation into a much smaller number of major centers of production. Luther’s movement created a new market that both subverted and energized this established economic geography. This reorientation of production owed a great deal to Luther’s own incisive, intuitive understanding of the potentialities of the new medium.
Dynamic Capability as a Theory of Competitive Advantage
Authors: Denrell Jerker , Powell Thomas C.
Published: March 2016

Dynamic capability is a theory of competitive advantage in rapidly changing environments. We reconcile this explanation with previous theories of competitive advantage, showing how it informs and complements explanations based on market positions, firm resources, and Schumpeterian creative destruction. We examine the scope conditions of dynamic capability; that is, when the theory has more and less explanatory power. We find that dynamic capability has greatest explanatory power when a partially foreseeable technological change is on the verge of transforming market competition; and less explanatory power when dynamic capabilities are not undervalued or scarce; when change is unforeseeable; when change is easily foreseeable; when the effect size of new capabilities is small; in industries subject to repeated technological shifts; and in markets that reward short bursts of extraordinary performance over long-term persistence. We discuss these scope conditions and show how dynamic capability combines with prior theories to explain competitive advantage in different industry contexts.
Islamic Law in Post-revolutionary Iran
Authors: Fujinaga Antonia Fraser
Published: March 2016

This article examines Islamic law in post-revolutionary Iran, with particular emphasis on areas where Islamic and Iranian law intersect. Before discussing the various manifestations of Islam in Iran, it traces the history of Iran’s adoption of Islamized laws. It then turns to the nature and history of the post-revolutionary Iranian constitution and constitutional law, along with the efforts of Iranian Islamic reformists and thinkers to conceptualize Islam so as to accommodate popular representation and adaptability to changing social and cultural preferences. It also considers the relationship between conformity to Shi‘a law (and/or its governmentally endorsed interpretations) on the one hand, and the exigencies of a modern state—including some responsiveness to popular and parliamentary demands for legal reform—on the other. Finally, the article looks at various areas where Islamic law intersects with Iranian law.
A Historiography of Islamic Law in the Mughal Empire
Authors: Pirbhai M. Reza
Published: March 2016

Whereas political and cultural histories of the Mughal Sultanate (1526–1858) abound, the study of Islamic law under the state’s auspices is less clearly drawn. This article considers the reasons behind the dearth by outlining the process by which major archival collections came into being and critically evaluating the secondary works produced over the last century and half. It argues that two factors are primarily responsible: 1) the qualitative and quantitative paucity of extant documentation as a consequence of no Mughal state archives and the fact that contemporary collections originated with British colonialism; 2) the approach too often taken by historians of South Asia. Early secondary works make little to no distinction between treatises reflexive of legal theory and practice, while many late works compensate by considering theory entirely divorced from Mughal practice. For the study of Islamic law under the Mughals to progress, practical and theoretical obstacles must be overcome.
Neo-Gricean Pragmatics
Authors: Huang Yan
Published: March 2016

The aim of this chapter is to provide a state-of-the-art survey of classical and especially neo-Gricean pragmatics, focusing on the bipartite model put forward by Horn and the trinitarian model advanced by Levinson. It assesses the role neo-Gricean pragmatics plays in effecting a radical simplification of the lexicon, semantics, and formal syntax in linguistic theory respectively, covering lexical narrowing, lexical cloning, lexical blocking, and lexicalization asymmetry in logical operators, and concentrating on pragmatic intrusion into what is said, Grice’s circle, and the pragmatics–semantics interface, and anaphora and binding.
Interlanguage Pragmatics
Authors: Félix-Brasdefer J. César
Published: March 2016

This chapter provides an overview and an assessment of central topics in interlanguage pragmatics (ILP). The chapter begins by defining the pragmatics for ILP, followed by a selective account of the main concepts covered in the field, such as pragmatic competence, the distinction between pragmalinguistics and sociopragmatics, second-language (L2) pragmatics, pragmatic transfer, pragmatic instruction, and types of pragmatic failure. Then, it describes and evaluates predominant theoretical and methodological approaches, as well as the methods generally used to collect data in ILP. The chapter also reviews research on pragmatic development, including longitudinal and cross-sectional studies, pedagogical intervention, study-abroad (SA) contexts, and pragmatic development as a result of incidental learning. The chapter ends with a discussion of future directions in ILP.
Treatment Processes and Outcomes in Psychology
Authors: Maltzman Sara
Published: March 2016

ThisOxford Handbook of Treatment Processes and Outcomes in Psychologyoffers a multidisciplinary, biopsychosocial approach to research and practice in psychology pertinent to applied settings. It is written for practitioners from varying disciplines and perspectives (e.g., counseling, clinical, school, and developmental psychology; social work), researchers in these areas, as well as oversight bodies (e.g., mental health clinics and government agencies) tasked with the oversight of mental health services provided to the communities they serve. Practitioners and researchers in various disciplines tend to be “siloed,” accessing a restricted literature that typically does not extend far beyond their area of study. The result is suboptimal exposure to an accurate science base that can inform practice and research. ThisHandbookpresents a multidisciplinary approach from experts in their respective fields to understanding clients and treatment across the life span. It includes detailed discussions in several chapters that expand on core areas of research and practice that already have a substantive research base, such as the therapeutic alliance, temperament, therapist variables, and career counseling. TheHandbookalso provides chapters in new areas of research (e.g., neuroimaging, the role of medications, and evaluating the placebo effect) to provide a data-based assessment of the current state of the research in these areas. ThisHandbookprovides “hands-on” guidance and suggestions, based on research, for identifying interventions that are effective, determining what factors can affect treatment effectiveness, and considerations for the evaluation of the provision of mental health services for children, adolescents, adults, and families at the case or aggregate level.
Western Theologies and Judaism in the Early Modern World
Authors: Burnett Stephen
Published: March 2016

This article examines how Western theologians of the seventeenth and eighteenth centuries perceived Jews and Judaism compared to their predecessors. It considers how Judaism was portrayed by Christian Hebraism during the period, before discussing Western theological references to Jews under the doctrine of scripture, controversial theology (including theological books written for missionary outreach to Jews), and eschatology. It also explores the challenges faced by theologians of the seventeenth and eighteenth centuries with respect to writing anti-Jewish polemics, with particular emphasis on how their works were influenced by the need to establish clear theological boundaries between themselves and Judaism, as well as other confessional churches, schismatics, anti-Trinitarians, and atheists. It comments on the thinking by most confessional theologians that a mass conversion of the Jews in the future would be one of the signs of the impending Last Judgment.
Cognitive Vulnerability and Unipolar Depression
Authors: Alloy Lauren B. , Abramson Lyn , Stange Jonathan , Salk Rachel
Published: March 2016

Maladaptive cognitive styles, including dysfunctional attitudes about our self-worth, the tendency to make negative inferences about the causes and consequences of negative events, and the tendency to ruminate about our sad mood, have been hypothesized to provide vulnerability to depression when individuals experience stressful life events. This chapter presents an overview of the three main cognitive vulnerability theories of depression, Beck’s Cognitive Theory, the Hopelessness Theory, and Response Styles Theory, which feature these three proposed cognitive vulnerabilities, respectively. The chapter describes each of these cognitive vulnerabilities, their measurement, and the types of research designs that have been employed to test the cognitive vulnerability theories. It also reviews the empirical evidence for each of these three forms of cognitive vulnerability to depression. Finally, the chapter highlights directions for further research.
Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish
Authors: Ingley Spencer J. , Johnson Jerald B.
Published: March 2016

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in
Brachyrhaphis
fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time.
Differential gene expression in seasonal sympatry: mechanisms involved in diverging life histories
Authors: Fudickar Adam M. , Peterson Mark P. , Greives Timothy J. , Atwell Jonathan W. , Bridge Eli S. , Ketterson Ellen D.
Published: March 2016

In an era of climate change, understanding the genetic and physiological mechanisms underlying flexibility in phenology and life history has gained greater importance. These mechanisms can be elucidated by comparing closely related populations that differ in key behavioural and physiological traits such as migration and timing of reproduction. We compared gene expression in two recently diverged dark-eyed Junco ( 
Junco hyemalis
) subspecies that live in seasonal sympatry during winter and early spring, but that differ in behaviour and physiology, despite exposure to identical environmental cues. We identified 547 genes differentially expressed in blood and pectoral muscle. Genes involved in lipid transport and metabolism were highly expressed in migrant juncos, while genes involved in reproductive processes were highly expressed in resident breeders. Seasonal differences in gene expression in closely related populations residing in the same environment provide significant insights into mechanisms underlying variation in phenology and life history, and have potential implications for the role of seasonal timing differences in gene flow and reproductive isolation.
Benton Seymour Rabinovitch. 19 February 1919 — 2 August 2014
Authors: Campbell Charles T. , Rabinovitch Ruth A.
Published: March 2016

Benton Seymour Rabinovitch was one of the pioneers of chemical dynamics. His brilliant experiments performed during his four decades as a Professor of Chemistry at the University of Washington in Seattle provided most of our early quantitative measurements of the efficiency with which energy is transferred between molecules in gas-phase molecule–molecule collisions and in collisions of molecules with solid surfaces. More importantly, his work provided quantitative estimates of the rates with which vibrational energy deposited locally within a molecule is redistributed among the many vibrational modes within that molecule, proving that the equilibration of this vibrational energy among these modes almost always occurs in approximately one picosecond. He further showed that this validates (in most cases) the assumptions of Rice–Ramsperger–Kassel–Marcus (RRKM) theory. He also developed several widely used mathematical shortcuts for using RRKM theory to make important predictions about physical chemistry. These shortcuts greatly increased both the applications and impact of RRKM theory, so that it has become one of the most important theories of physical chemistry. It continues to guide much of our fundamental understanding of chemical dynamics and reaction kinetics even today. In addition to being a great scientist, Seymour Rabinovitch was a devoted husband and father. He raised four accomplished children, and later in life became an expert in the art of silversmithing, a writer of children's books, and a philanthropist. His offspring are following beautifully in his footsteps in their kindness to fellow human beings, their excellence in scholarship, science and art, and in their energetic dedication to improving the world through teaching, research, service and philanthropy. The same can be said for his academic offspring as well.
Alan Carrington CBE. 6 January 1934 — 31 August 2013
Authors: Buckingham A. D. , Saykally R. J.
Published: March 2016

Alan Carrington was an outstanding physical chemist who made important contributions to molecular spectroscopy. During his distinguished career in the universities of Southampton, Cambridge and Oxford he was a pioneer in the fields of electron paramagnetic resonance spectroscopy of doped single crystals, solutions of organic radicals, and especially the high resolution spectroscopy of gaseous free-radicals and ions. He wrote three books and was an excellent teacher and lecturer. His honours included the Davy Medal, the Faraday Medal of the Royal Society of Chemistry, and election as a Foreign Associate of the National Academy of Sciences.
Evolutionary diversification of retinoic acid receptor ligand-binding pocket structure by molecular tinkering
Authors: Gutierrez-Mazariegos Juliana , Nadendla Eswar Kumar , Studer Romain A. , Alvarez Susana , de Lera Angel R. , Kuraku Shigehiro , Bourguet William , Schubert Michael , Laudet Vincent
Published: March 2016

Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication–degeneration–complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RARα, RARβ and RARγ. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RARα and RARβ. In contrast, none of the cyclostome receptors studied showed any RARγ-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor–ligand interactions of NRs following WGDs.
The causal meaning of Hamilton’s rule
Authors: Okasha Samir , Martens Johannes
Published: March 2016

Hamilton’s original derivation of his rule for the spread of an altruistic gene (
rb
>
c
) assumed additivity of costs and benefits. Recently, it has been argued that an exact version of the rule holds under non-additive pay-offs, so long as the cost and benefit terms are suitably defined, as partial regression coefficients. However, critics have questioned both the biological significance and the causal meaning of the resulting rule. This paper examines the causal meaning of the generalized Hamilton’s rule in a simple model, by computing the effect of a hypothetical experiment to assess the cost of a social action and comparing it to the partial regression definition. The two do not agree. A possible way of salvaging the causal meaning of Hamilton’s rule is explored, by appeal to R. A. Fisher’s ‘average effect of a gene substitution’.
A time-domain Kirchhoff formula for the convective acoustic wave equation
Authors: Ghorbaniasl Ghader , Siozos-Rousoulis Leonidas , Lacor Chris
Published: March 2016

Kirchhoff’s integral method allows propagated sound to be predicted, based on the pressure and its derivatives in time and space obtained on a data surface located in the linear flow region. Kirchhoff’s formula for noise prediction from high-speed rotors and propellers suffers from the limitation of the observer located in uniform flow, thus requiring an extension to arbitrarily moving media. This paper presents a Kirchhoff formulation for moving surfaces in a uniform moving medium of arbitrary configuration. First, the convective wave equation is derived in a moving frame, based on the generalized functions theory. The Kirchhoff formula is then obtained for moving surfaces in the time domain. The formula has a similar form to the Kirchhoff formulation for moving surfaces of Farassat and Myers, with the presence of additional terms owing to the moving medium effect. The equation explicitly accounts for the influence of mean flow and angle of attack on the radiated noise. The formula is verified by analytical cases of a monopole source located in a moving medium.
Mechanosensation in an adipose fin
Authors: Aiello Brett R. , Stewart Thomas A. , Hale Melina E.
Published: March 2016

Adipose fins are found on approximately 20% of ray-finned fish species. The apparently rudimentary anatomy of adipose fins inspired a longstanding hypothesis that these fins are vestigial and lack function. However, adipose fins have evolved repeatedly within Teleostei, suggesting adaptive function. Recently, adipose fins were proposed to function as mechanosensors, detecting fluid flow anterior to the caudal fin. Here we test the hypothesis that adipose fins are mechanosensitive in the catfishCorydoras aeneus. Neural activity, recorded from nerves that innervate the fin, was shown to encode information on both movement and position of the fin membrane, including the magnitude of fin membrane displacement. Thus, the adipose fin ofC. aeneusis mechanosensitive and has the capacity to function as a ‘precaudal flow sensor’. These data force re-evaluation of adipose fin clipping, a common strategy for tagging fishes, and inform hypotheses of how function evolves in novel vertebrate appendages.
Within-host competition and drug resistance in the human malaria parasite
Plasmodium falciparum
Authors: Bushman Mary , Morton Lindsay , Duah Nancy , Quashie Neils , Abuaku Benjamin , Koram Kwadwo A. , Dimbu Pedro Rafael , Plucinski Mateusz , Gutman Julie , Lyaruu Peter , Kachur S. Patrick , de Roode Jacobus C. , Udhayakumar Venkatachalam
Published: March 2016

Infections with the malaria parasite
Plasmodium falciparum
typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341
P. falciparum
infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.
Silent oceans: ocean acidification impoverishes natural soundscapes by altering sound production of the world's noisiest marine invertebrate
Authors: Rossi Tullio , Connell Sean D. , Nagelkerken Ivan
Published: March 2016

Soundscapes are multidimensional spaces that carry meaningful information for many species about the location and quality of nearby and distant resources. Because soundscapes are the sum of the acoustic signals produced by individual organisms and their interactions, they can be used as a proxy for the condition of whole ecosystems and their occupants. Ocean acidification resulting from anthropogenic CO
2
emissions is known to have profound effects on marine life. However, despite the increasingly recognized ecological importance of soundscapes, there is no empirical test of whether ocean acidification can affect biological sound production. Using field recordings obtained from three geographically separated natural CO
2
vents, we show that forecasted end-of-century ocean acidification conditions can profoundly reduce the biological sound level and frequency of snapping shrimp snaps. Snapping shrimp were among the noisiest marine organisms and the suppression of their sound production at vents was responsible for the vast majority of the soundscape alteration observed. To assess mechanisms that could account for these observations, we tested whether long-term exposure (two to three months) to elevated CO
2
induced a similar reduction in the snapping behaviour (loudness and frequency) of snapping shrimp. The results indicated that the soniferous behaviour of these animals was substantially reduced in both frequency (snaps per minute) and sound level of snaps produced. As coastal marine soundscapes are dominated by biological sounds produced by snapping shrimp, the observed suppression of this component of soundscapes could have important and possibly pervasive ecological consequences for organisms that use soundscapes as a source of information. This trend towards silence could be of particular importance for those species whose larval stages use sound for orientation towards settlement habitats.
Cuttlefish see shape from shading, fine-tuning coloration in response to pictorial depth cues and directional illumination
Authors: Zylinski Sarah , Osorio D. , Johnsen Sonke
Published: March 2016

Humans use shading as a cue to three-dimensional form by combining low-level information about light intensity with high-level knowledge about objects and the environment. Here, we examine how cuttlefishSepia officinalisrespond to light and shadow to shade the white square (WS) feature in their body pattern. Cuttlefish display the WS in the presence of pebble-like objects, and they can shade it to render the appearance of surface curvature to a human observer, which might benefit camouflage. Here we test how they colour the WS on visual backgrounds containing two-dimensional circular stimuli, some of which were shaded to suggest surface curvature, whereas others were uniformly coloured or divided into dark and light semicircles. WS shading, measured by lateral asymmetry, was greatest when the animal rested on a background of shaded circles and three-dimensional hemispheres, and less on plain white circles or black/white semicircles. In addition, shading was enhanced when light fell from the lighter side of the shaded stimulus, as expected for real convex surfaces. Thus, the cuttlefish acts as if it perceives surface curvature from shading, and takes account of the direction of illumination. However, the direction of WS shading is insensitive to the directions of background shading and illumination; instead the cuttlefish tend to turn to face the light source.
LoLoPicker: Detecting Low Allelic-Fraction Variants in Low-Quality Cancer Samples
Authors: Carrot-Zhang Jian , Majewski Jacek
Published: March 2016

We developed an efficient tool dedicated to call somatic variants from whole-exome sequencing (WES) data using tumor and its matched normal tissue, plus a user-defined control panel of non-cancer samples. Compared with other methods, we showed superior performance of LoLoPicker with significantly improved specificity. The algorithm of LoLoPicker is particularly useful for calling variants from low-quality cancer samples such as formalin-fixed and paraffinembedded (FFPE) samples.

Implementation and Availability

The main scripts are implemented in Python 2.7.8 and the package is released athttps://github.com/jcarrotzhang/LoLoPicker.
Prediction of kinase-specific phosphorylation sites through an integrative model of protein context and sequence
Authors: Patrick Ralph , Horin Coralie , Kobe Bostjan , Lê Cao Kim-Anh , Bodén Mikael
Published: March 2016

The identification of kinase substrates and the specific phosphorylation sites they regulate is an important factor in understanding protein function regulation and signalling pathways. Computational prediction of kinase targets – assigning kinases to putative substrates, and selecting from protein sequence the sites that kinases can phosphorylate – requires the consideration of both the cellular context that kinases operate in, as well as their binding affinity. This consideration enables investigation of how phosphorylation influences a range of biological processes.

We report here a novel probabilistic model for the classification of kinase-specific phosphorylation sites from sequence across three model organisms: human, mouse and yeast. The model incorporates position-specific amino acid frequencies, and counts of co-occurring amino acids from kinase binding sites in a kinase‐ and family-specific manner. We show how this model can be seamlessly integrated with protein interactions and cell-cycle abundance profiles. When evaluating the prediction accuracy of our method, PhosphoPICK, on an independent hold-out set of kinase-specific phosphorylation sites, we found it achieved an average specificity of 97% while correctly predicting 32% of true positives. We also compared PhosphoPICK’s ability, through cross-validation, to predict kinase-specific phosphorylation sites with alternative methods, and found that at high levels of specificity PhosphoPICK outperforms alternative methods for most comparisons made.

We investigated the relationship between experimentally confirmed phosphorylation sites and predicted nuclear localisation signals by predicting the most likely kinases to be regulating the phosphorylated residues immediately upstream or downstream from the localisation signal. We show that kinases PKA, Akt1 and AurB have an over-representation of predicted binding sites at particular positions downstream from predicted nuclear localisation signals, demonstrating an important role for these kinases in regulating the nuclear import of proteins.

PhosphoPICK is freely available online as a web-service athttp://bioinf.scmb.uq.edu.au/phosphopick.
Proteolytic cleavage of proBDNF into mature BDNF in the basolateral amygdala is necessary for defeat-induced social avoidance
Authors: Dulka Brooke N. , Ford Ellen C. , Lee Melissa A. , Donnell Nathaniel J. , Goode Travis D. , Prosser Rebecca , Cooper Matthew A.
Published: March 2016

Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in the BLA/central amygdala. We also showed that blocking plasmin in the BLA with microinjection of α2-antiplasmin immediately following social defeat decreases social avoidance 24 h later. These data suggest the proteolytic cleavage of BDNF in the BLA is necessary for defeat-induced social avoidance.
Phosphorylation of K+ channels at single residues regulates memory formation
Authors: Vernon Jeffrey , Irvine Elaine E. , Peters Marco , Jeyabalan Jeshmi , Giese K. Peter
Published: March 2016

Phosphorylation is a ubiquitous post-translational modification of proteins, and a known physiological regulator of K+ channel function. Phosphorylation of K+ channels by kinases has long been presumed to regulate neuronal processing and behavior. Although circumstantial evidence has accumulated from behavioral studies of vertebrates and invertebrates, the contribution to memory of single phosphorylation sites on K+ channels has never been reported. We have used gene targeting in mice to inactivate protein kinase A substrate residues in the fast-inactivating subunit Kv4.2 (T38A mutants), and in the small-conductance Ca2+-activated subunit SK1 (S105A mutants). Both manipulations perturbed a specific form of memory, leaving others intact. T38A mutants had enhanced spatial memory for at least 4 wk after training, whereas performance in three tests of fear memory was unaffected. S105A mutants were impaired in passive avoidance memory, sparing fear, and spatial memory. Together with recent findings that excitability governs the participation of neurons in a memory circuit, this result suggests that the memory type supported by neurons may depend critically on the phosphorylation of specific K+ channels at single residues.
Sustainable Lean in psychiatry? Assessment through socio-technical principles
Authors: Lindskog Pernilla , Vänje Annika , Törnkvist Åsa , Eklund Jörgen
Published: March 2016

Purpose

– This paper aims to identify conditions affecting sustainability of Lean implementations in Swedish psychiatric healthcare, from a socio-technical perspective.

Design/methodology/approach

– Longitudinal focus group interviews were conducted with 24 first-line managers within Swedish psychiatric healthcare. The analysis was made using Cherns’ ten socio-technical principles and a framework for sustainable development work in healthcare.

Findings

– The most critical socio-technical principles for a sustainable Lean implementation were boundary location; power and authority; and compatibility. At hospital level, socio-technical principles were inhibited by the weak ownership of the Lean implementation. However, strong ownership at division level meant the same principles were supported. Unclear goals made follow-ups difficult which had negative effects on the learning processes in the Lean implementation. The role and responsibility of first-line managers were unclear in that they perceived they lacked power and authority resulting in negative effects on the participation – an important sustainability concept.

Originality/value

– Empirically based papers assessing Lean implementations in psychiatry are rare. This study is a contribution to the research area of sustainable Lean implementations in healthcare. The practical implication of this study is that decision makers, senior managers, first-line managers and psychiatrists can be supported in reaching sustainable implementations of Lean.
Towards developing a model to assess the experience of visitors of the Janadriyah festival, Saudi Arabia
Authors: Abdelazim Tarek Sayed , Alajloni Abdallah Ali
Published: March 2016

Purpose

– The purpose of this paper is to evaluate the experience of visitors with the Janadriyah festival.

Design/methodology/approach

– An on-site intercept survey was conducted among a random sample of visitors of the festival. The survey was conducted by two field researchers between February 10 and February 25, 2014. A self-administered questionnaire was distributed only to those who agreed to respond to the survey. Out of 200 questionnaires distributed, 28 were incomplete and thus eliminated from the study. As a result, 172 questionnaires were accepted for the purpose of final analysis, representing a response rate of 86 percent.

Findings

– There is a statistically significant contribution for both the first motivation (I participate in the Janadriyah festival to increase my cultural knowledge) and the fifth one (I participate in the Janadriyah festival to see new and different things and to enjoy a unique atmosphere). There is a statistically significant relationship between the most of services provided and the level of satisfaction. As well as, there is a statistically significant relationship between the perception and the level of satisfaction, also with the word of mouth communication. Finally, the results shown that behavioral intention had a positive influence on word of mouth communication.

Research limitations/implications

– There were time limits to this study as the research was conducted during the organization of the Janadriyah festival during its 26th session (February-March 2014).The research was also limited by place as it was conducted at the capital of Saudi Arabia, Janadriyah province.

Practical implications

– The model of the study could be applied in similar studies for different festivals all over the world.

Social implications

– Increasing the promotional efforts to attract more visitors from different regions in the world. As it is observed that the vast majority of participants in the Janadriyah festival are local residents. In addition, there is a need to organize training programs to all staff participating in the organization of the festival supervised by academics and professionals. Organizing seminars during the festival in order to increase the awareness of local residents with importance of the cultural heritage and how to keep it. And at the end, the program of the festival has to be updated from one session to another in order to attract more attendees.

Originality/value

– The integrated model of the study represent an added value to the research in the field of tourism festivals.