bluuebunny/crossref_metadata_2025 huggingface dataset:
Target selection by natural and redesigned PUF proteins
Authors: Porter Douglas F. , Koh Yvonne Y. , VanVeller Brett , Raines Ronald T. , Wickens Marvin
Published: December 2015

Significance

Pumilio/fem-3 mRNA binding factor (PUF) proteins have become a leading scaffold in designing proteins to bind and control RNAs at will. We analyze the effects of that reengineering across the transcriptome in vivo for the first time to our knowledge. We show that yeast Puf2p, a noncanonical PUF protein, binds more than 1,000 mRNA targets. Puf2p binds multiple UAAU elements, unlike canonical PUF proteins. We design a modified Puf2p to bind UAAG rather than UAAU, which allows us to align the protein with the binding site. In vivo, the redesigned protein binds UAAG sites. Its altered specificity redistributes the protein away from 3′UTRs, such that the protein tracks with its sites, binds throughout the mRNA and represses a novel RNA network.
Evolution of stickleback in 50 years on earthquake-uplifted islands
Authors: Lescak Emily A. , Bassham Susan L. , Catchen Julian , Gelmond Ofer , Sherbick Mary L. , von Hippel Frank A. , Cresko William A.
Published: December 2015

Significance

On several Alaskan islands, phenotypically variable threespine stickleback fish now live in ponds that were formed during uplift caused by the 1964 Great Alaska Earthquake. We analyzed phenotypic and genome-wide genetic divergence of resident freshwater and oceanic threespine stickleback populations from three islands. These data support the hypothesis that the freshwater populations evolved repeatedly from their oceanic ancestors in the past half-century, and have differentiated to nearly the same extent as populations that were founded thousands of years ago. This work raises the possibility that much of the evolution that occurs when oceanic stickleback invade fresh water takes place in fewer than 50 generations after colonization, rather than gradually over thousands of years.
Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome
Authors: Rath Sneha , Donovan Jesse , Whitney Gena , Chitrakar Alisha , Wang Wei , Korennykh Alexei
Published: December 2015

Significance

The mammalian innate immune system recognizes double-stranded RNA (dsRNA) as a signature of infections and cell damage. Cells exposed to dsRNA release interferons to activate protective programs in surrounding tissues. One of these protective programs triggers regulated decay of intracellular RNA by the pseudokinase/endoribonuclease RNase L. Here we map the pathway of this RNA decay transcriptome-wide and identify groups of selectively destabilized human messenger RNAs. We show that RNA decay by RNase L has an important role in homeostasis and serves as a suppressor of cell adhesion. Our work defines the targets of RNase L and clarifies the role of the dsRNA-activated messenger RNA decay in the interferon response.
Dogs lap using acceleration-driven open pumping
Authors: Gart Sean , Socha John J. , Vlachos Pavlos P. , Jung Sunghwan
Published: December 2015

Significance

Cats and dogs are assumed to drink similarly, but little is known about the actual physical mechanisms that dogs use to transport fluids when lapping. We observed the drinking behavior of a wide range of dogs across breeds and body size, and used physical experiments to mimic the motion of a dog’s tongue as it exits the water. Dogs accelerate the tongue upward more quickly than do cats, and then time their bite to coincide with the pinch-off of the column. The everyday experience of dogs as messy drinkers results from the backward curl of the tongue, which increases the size of the water column and thus enables dogs to drink more per lap than with a straight tongue.
High-energy resolution X-ray absorption and emission spectroscopy reveals insight into unique selectivity of La-based nanoparticles for CO2
Authors: Hirsch Ofer , Kvashnina Kristina O. , Luo Li , Süess Martin J. , Glatzel Pieter , Koziej Dorota
Published: December 2015

Significance

CO2has become a challenge for our society and we have to develop new materials for its photo-/electrocatalysis, chemoresistive sensing, and storage. Particularly, for the variety of electrochemical applications the selective interaction of CO2and charge transfer with solids is in the foreground, but their origins are poorly understood. Our story will undoubtedly showcase how to access the key information, which is relevant for electrochemical application from in situ X-ray absorption spectroscopy/X-ray emission spectroscopy studies.
Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators
Authors: Bogerd Hal P. , Kornepati Anand V. R. , Marshall Joy B. , Kennedy Edward M. , Cullen Bryan R.
Published: December 2015

Significance

Cells encode several effective antiviral proteins, yet these are sometimes not expressed in infected cells. Using a synthetic transcriptional activator based on the bacterial RNA-guided DNA binding protein Cas9, we demonstrate the efficient induction of two antiviral effectors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally express neither protein. A3G is susceptible to degradation by the HIV-1 Vif protein, whereas A3B is resistant to Vif. As a result, only the induced A3B inhibited wild-type HIV-1 infectivity. However, both induced factors blocked the replication of a Vif-deficient HIV-1 mutant. These data demonstrate that Cas9-derived transcription factors can effectively induce human genes that regulate virus replication, thus setting the scene for their use in genomic screens to identify such factors.
Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly
Authors: Lee Il-Hyung , Kai Hiroyuki , Carlson Lars-Anders , Groves Jay T. , Hurley James H.
Published: December 2015

Significance

The endosomal sorting complex required for transport (ESCRT) proteins remodel and sever membranes in a wide range of biology, including HIV budding. Electron microscopy has shown that ESCRT-III is often found in contact with concave (negatively curved) membrane surfaces. It has not been possible until now to determine whether the ESCRTs have an inherent preference for binding to concave membrane because it is difficult to make nanoscale concave membranes. Here we have made such membranes on the dimensions of an HIV budding site. We show that ESCRT-III assembly begins (nucleates) much faster on concave membranes, which explains why this complex is recruited in a rapid burst late in HIV budding.
Networks of military alliances, wars, and international trade
Authors: Jackson Matthew O. , Nei Stephen
Published: December 2015

Significance

The incidence of interstate wars has dropped dramatically over time: The number of wars per pair of countries per year from 1950 to 2000 was roughly a 10th as high as it was from 1820 to 1949. This significant decrease in the frequency of wars correlates with a substantial increase in the number of military alliances per country and the stability of those alliances. We show that one possible explanation of this is an accompanying expansion of international trade. Increased trade decreases countries’ incentives to attack each other and increases their incentives to defend each other, leading to a stable and peaceful network of military and trade alliances that is consistent with observed data.
Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals
Authors: Fristoe Trevor S. , Burger Joseph R. , Balk Meghan A. , Khaliq Imran , Hof Christian , Brown James H.
Published: December 2015

Significance

How different kinds of organisms adapt to environmental temperature is central to understanding how they respond to past, present, and future climate change. We applied the Scholander–Irving model of thermoregulation to data on hundreds of species of birds and mammals to assess the contributions of three avenues of adaptation to environmental temperature: body size, basal metabolic rate (
BMR
), and thermal conductance. Adaptation via body size is limited; the entire ranges of body sizes of birds and mammals occur in nearly all climatic regimes. Using physiological and environmental data for 211 bird and 178 mammal species, we demonstrate that birds and mammals have adapted to geographic variation in environmental temperature regimes by concerted changes in both
BMR
and thermal conductance.
Transnational Public Attention in European Club Football: Current trends and driving forces
Authors: Mutz Michael
Published: December 2015

Professional football is a highly globalized area. The paper analyses the impact of globalization on football audiences in European countries. It is argued that in the course of globalization, people are not only thrown into a transnational lifestyle, but may also develop a growing interest in what is going on outside their domestic territory. With regard to football, it is hypothesized that audiences may direct more and more attention to high-class football leagues and clubs abroad. This presumed shift of attention is empirically investigated with a new indicator: search engine queries. It is argued that queries addressing football clubs in foreign countries are expressions of transnational attention. These transnational queries are systematically analysed over a period of seven seasons (2005/2006–2011/2012). Results indicate that public attention to foreign football clubs has indeed increased over time, particularly in those countries with weaker domestic football leagues. Furthermore, the fluctuation of attention to these clubs can be explained systematically: attention increases with (a) the success of a club in European and national competitions, (b) the success of domestic players in an expatriate club and (c) the number of matches against domestic clubs in European club competitions. Although transnational attention is generally on the rise, its change over time still seems to depend largely on national identification.
Flavobacteria Isolated from the Milt of Feral Chinook Salmon of the Great Lakes
Authors: Loch T P , Faisal M
Published: December 2015

Fish diseases caused by multiple genera within the family Flavobacteriaceae (Phylum Bacteroidetes) are a major impediment to farmed teleosts. At least one fish-pathogenic flavobacterial species (e.g., Flavobacterium psychrophilum) is transmitted from parents to progeny via infected sexual products, but the majority of research has focused on the role that ovarian fluid and eggs play in bacterial transmission. However, a handful of studies have revealed that milt can also harbor F. psychrophilum. Herein, we report on the isolation and molecular identification of multiple Flavobacterium and Chryseobacterium spp. from the milt of feral Great Lakes Chinook Salmon Oncorhynchus tshawytscha. Some of the milt-associated flavobacteria were identified as well-known fish pathogens (e.g., F. columnare, etiological agent of columnaris disease), whereas others were most similar to emerging fish pathogens (e.g., C. piscium) or were distinct from all our described Flavobacterium and Chryseobacterium spp., according to partial 16S rRNA gene sequencing and phylogenetic analyses. Although systemic F. psychrophilum infections were detected in the kidneys of 35% of the 120 sampled male Chinook Salmon, the bacterium was never detected in the milt. The findings of this study highlight the role that milt can play in the transmission of a diversity of flavobacterial species.
The relocation of a repertoire of collective action: Maidan 2013
Authors: Oleinik Anton , Strelkova Olga
Published: December 2015

The Ukrainian protests of November–December 2013 owed their success to the relocation of modular repertoires of contention (street protests, sit-ins and barricades) onto Ukrainian soil and their adaptation to local traditions. Particular attention is given to Veche (a gathering of community members) and Sich (a military camp of Cossacks). The communitarian model of institutional transfers is better suited for the Ukrainian case than the entrepreneurial model: the protests were initiated, organized and sustained by ordinary people as opposed to the leaders of the opposition parties. Three mass surveys conducted during the protests and a series of qualitative semi-structured interviews (N = 31) provide data for the analysis.
The microtubule catastrophe promoter Sentin delays stable kinetochore–microtubule attachment in oocytes
Authors: Głuszek A. Agata , Cullen C. Fiona , Li Wenjing , Battaglia Rachel A. , Radford Sarah J. , Costa Mariana F. , McKim Kim S. , Goshima Gohta , Ohkura Hiroyuki
Published: December 2015

The critical step in meiosis is to attach homologous chromosomes to the opposite poles. In mouse oocytes, stable microtubule end-on attachments to kinetochores are not established until hours after spindle assembly, and phosphorylation of kinetochore proteins by Aurora B/C is responsible for the delay. Here we demonstrated that microtubule ends are actively prevented from stable attachment to kinetochores until well after spindle formation in Drosophila melanogaster oocytes. We identified the microtubule catastrophe-promoting complex Sentin-EB1 as a major factor responsible for this delay. Without this activity, microtubule ends precociously form robust attachments to kinetochores in oocytes, leading to a high proportion of homologous kinetochores stably attached to the same pole. Therefore, regulation of microtubule ends provides an alternative novel mechanism to delay stable kinetochore–microtubule attachment in oocytes.
Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles
Authors: Hatlen Megan A. , Arora Kanika , Vacic Vladimir , Grabowska Ewa A. , Liao Willey , Riley-Gillis Bridget , Oschwald Dayna M. , Wang Lan , Joergens Jacob E. , Shih Alan H. , Rapaport Franck , Gu Shengqing , Voza Francesca , Asai Takashi , Neel Benjamin G. , Kharas Michael G. , Gonen Mithat , Levine Ross L. , Nimer Stephen D.
Published: December 2015

t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO–driven mouse models of leukemia with the mutational profiles of human AML patients. We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo. This integrative genetic profiling approach allowed us to accurately predict cooperating events in t(8;21)+ AML in a robust and unbiased manner, while also revealing functional convergence in mouse and human AML.
Productivity, Export, and Environmental Performance: Air Pollutants in the United States
Authors: Cui Jingbo , Lapan Harvey , Moschini GianCarlo
Published: December 2015

This paper studies the firm‐level relationship among productivity, decision to export, and environmental performance. The emerging theoretical and empirical literature suggests that trade has an important role in determining firms' heterogeneity: increased openness to trade induces a reallocation effect that increases within‐industry efficiency, thereby linking firms' decisions to export and adopt newer (and cleaner) technology. We argue that this framework provides the following empirically‐relevant predictions: there is an inverse relationship between firm productivity and pollution emissions per unit output; exporting firms have lower emissions per unit output; and larger firms have a lower emission intensity. To examine these implications empirically, we have assembled a uniquely detailed dataset of the U.S. manufacturing industry for the years 2002, 2005, and 2008 by matching facility‐level air emission data from the U.S. Environmental Protection Agency with the facility's economic characteristics contained in the National Establishment Time Series database. The strategy is to first estimate a facility‐level total factor productivity parameter as a plant‐specific fixed effect. We then investigate how this estimated productivity parameter correlates with emission intensity on a pollutant‐by‐pollutant basis. Our empirical findings support the hypotheses suggested by the conceptual model. For each criteria air pollutant considered, we find a significant negative correlation between estimated facility productivity and emission intensity. Conditional on a facility's estimated productivity and other controls, exporting facilities have significantly lower emissions per value of sales than non‐exporting facilities in the same industry. We also find that plant size is negatively and significantly related to emission intensity for all pollutants.
DNAshapeR: an R/Bioconductor package for DNA shape prediction and feature encoding
Authors: Chiu Tsu-Pei , Comoglio Federico , Zhou Tianyin , Yang Lin , Paro Renato , Rohs Remo
Published: December 2015

Summary: DNAshapeR predicts DNA shape features in an ultra-fast, high-throughput manner from genomic sequencing data. The package takes either nucleotide sequence or genomic coordinates as input and generates various graphical representations for visualization and further analysis. DNAshapeR further encodes DNA sequence and shape features as user-defined combinations of k-mer and DNA shape features. The resulting feature matrices can be readily used as input of various machine learning software packages for further modeling studies.

Availability and implementation: The DNAshapeR software package was implemented in the statistical programming language R and is freely available through the Bioconductor project at https://www.bioconductor.org/packages/devel/bioc/html/DNAshapeR.html and at the GitHub developer site, http://tsupeichiu.github.io/DNAshapeR/.

Contact:  rohs@usc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Ocean acidification does not alter grazing in the calanoid copepods Calanus finmarchicus and Calanus glacialis
Authors: Hildebrandt Nicole , Sartoris Franz J. , Schulz Kai G. , Riebesell Ulf , Niehoff Barbara
Published: December 2015

It is currently under debate whether organisms that regulate their acid–base status under environmental hypercapnia demand additional energy. This could impair animal fitness, but might be compensated for via increased ingestion rates when food is available. No data are yet available for dominant Calanus spp. from boreal and Arctic waters. To fill this gap, we incubated Calanus glacialis at 390, 1120, and 3000 µatm for 16 d with Thalassiosira weissflogii (diatom) as food source on-board RV Polarstern in Fram Strait in 2012. Every 4 d copepods were subsampled from all CO2 treatments and clearance and ingestion rates were determined. During the SOPRAN mesocosm experiment in Bergen, Norway, 2011, we weekly collected Calanus finmarchicus from mesocosms initially adjusted to 390 and 3000 µatm CO2 and measured grazing at low and high pCO2. In addition, copepods were deep frozen for body mass analyses. Elevated pCO2 did not directly affect grazing activities and body mass, suggesting that the copepods did not have additional energy demands for coping with acidification, neither during long-term exposure nor after immediate changes in pCO2. Shifts in seawater pH thus do not seem to challenge these copepod species.
Respiratory System
Authors: Koka Anjali , Eastburn Elizabeth C. , Park Raymond
Published: December 2015

This chapter contains 24 questions relevant for the Pediatric Subspecialty Exam about the topic of the respiratory system.
Genetics
Authors: Hoagland Monica A.
Published: December 2015

This chapter contains 31 questions relevant for the Pediatric Subspecialty Exam about the topic of genetics.
The Private Sector
Authors: Kumar Rajiv
Published: December 2015

This chapter examines the role of the Indian private sector in shaping the country’s foreign policy. It argues that the private sector has limited experience and capacity to influence the course of foreign policy. Barring certain areas such as Information Technology and IT enabled services, the private sector has not impacted much on India’s engagement with other countries and international institutions. Although the private sector plays an increasing role in Track II initiatives, its role in shaping policy remains limited. The chapter analyses the reasons for this and contends that the private sector needs to enhance its own capacity before it call pull its weight on matters of foreign policy. In any event, as India’s economy integrates ever more deeply with the global economy, the Indian private sector will play an increasingly important role in framing and enabling India’s external relations.
Five Approaches to the Study of Indian Foreign Policy
Authors: Bajpai Kanti
Published: December 2015

The study of Indian foreign policy goes back to the late 1940s and has resulted in a large amount of publishing in both India and abroad. What are the major approaches to the study of Indian foreign policy? By ‘approach’ is meant a broad orientation in a field of study, in particular the leading questions and interpretive lenses. An approach is not a theory; it is closer to the notion of ‘paradigm’. It encompasses the dominant set of questions and the ways of answering those questions that prevail in an intellectual field. In this case, Indian foreign policy studies has been substantially focused on relations with Pakistan, China, and the United States and why India has been in ‘protracted conflict’ with these three powers.
Mother India and Her Children Abroad
Authors: Varadarajan Latha
Published: December 2015

This chapter looks into the historical evolution of the relationship between the Indian state and the Indian diaspora to explain both the nature of the diaspora itself as well as the ways in which it has served to influence Indian foreign policy. Briefly tracing the complex history of colonial and post-colonial migrations, the chapter first makes the claim that despite a common origin, there exist very diverse emigrant communities with distinct political trajectories and socio-economic interests. Therefore, one should be cautious about framing the Indian diaspora as a unitary actor that has consciously and effectively shaped foreign policy. Beyond that, it also argues that despite specific moments when the concerns of the diaspora seemed to be prominent in foreign policy deliberations, the diaspora as a whole has been and continues to be marginal in the formulation of India’s foreign policy.
Indian Scientists in Defence and Foreign Policy
Authors: Prabhu Jaideep A.
Published: December 2015

This chapter shows how India’s scientists played an important role in policy-making. As science evolved to play a prominent role in the functioning of the modern state, its practitioners also gained importance, particularly those involved in defence research. India’s independence and modernization overlapped with the growth of international technocracy, shaping the relations between politics, the laboratory, and international law. Indian scientists grappled with the nuclear Janus as much as their Western counterparts, and their leaders had to balance the use of science for development and to make weapons of war. The importance of technology to the nation-building project as well as the bitter memories of colonialism informed Indian policy on issues such as nuclear non-proliferation and missile development that remain with us today. In fact, it has become impossible to separate science from its policy implications in the modern state.
India’s Policy Toward Pakistan
Authors: Basrur Rajesh
Published: December 2015

India’s most difficult foreign policy challenge has been Pakistan. At one level, the relationship has been managed reasonably well given the fundamental contradiction between India’s status quo-ist approach on Kashmir and Pakistan’s determination to alter the status quo. At another, Indian policy-makers’ inability to meet the challenge effectively reflects the constraints imposed by major policy choices. Jawaharlal Nehru opted for a set of ‘independent’ strategic and economic policies that congealed into ‘non-alignment’ and ‘self-sufficiency’. This left India militarily and economically weak and unable to counter Pakistan’s sustained bid to wrest Kashmir. A later set of choices encompasses failure to anticipate the consequences of Pakistan’s acquisition of nuclear capability, reluctance to match Islamabad’s asymmetric strategy of pressurizing India, and a tendency to slip back into the autonomy-oriented policy template of the Cold War era. Consequently, India’s capacity to fashion an optimal policy towards Pakistan continues to be significantly constrained.
Western Europe
Authors: Wagner Christian
Published: December 2015

India has long-standing relations with Western Europe. The Strategic Partnership Agreement of 2004 with the European Union and similar agreements with individual European states form the institutional basis for economic, political, military, technological, and cultural cooperation with India. But despite common interests in many areas, the strategic perspectives remain limited because of structural constraints in India and Western Europe. Even after the Treaty of Lisbon, the foreign policy of the EU will be shared between Brussels and the member states. India’s foreign policy is handled mostly by the under-staffed Ministry of External Affairs. This is far from being adequate to cope with the requirements of an interdependent global system and India’s own aspirations to play a more important role. Hence, only if both sides understand the structural constraints and limitations of the other, will the partnership flourish on a more realistic basis.
Unbreakable Bond
Authors: Xavier Constantino
Published: December 2015

Anchored in centuries of exchanges across the Western Indian Ocean, India’s relations with Africa have recently entered a new phase. New Delhi’s stakes in the continent now include accessing mineral resources, developing investment and trade potential, the security of East Africa’s sea lines of communication, protecting the Indian diaspora, enlisting diplomatic support for its multilateral stances, and also a competitive dynamic with China and other rising powers. This chapter reviews these various drivers, as well as the domestic debate on an ideal Africa policy. The chapter also discusses six areas where India may develop a long-term comparative advantage over its competitors.
India and Global Governance
Authors: Chitalkar Poorvi , Malone David M.
Published: December 2015

India’s engagement with the institutions and norms of global governance has evolved significantly since independence in 1947. This chapter traces the evolution—beginning with early engagement with international organizations under Nehru, to the waning of its enthusiasm for multilateralism in the 1960s and 1970s, and its struggle for greater voice and recognition internationally in the twenty-first century. Through the prism of its quest for a permanent seat in the UN Security Council, its approach to climate change negotiations, global economic diplomacy, and its engagement with global norms, this chapter traces India’s rise as a vital player in the rebalancing of international relations in a multipolar world. However, despite its tremendous progress, some ongoing challenges continue to constrain India’s meaningful participation in global governance at times. The chapter concludes with an assessment of India’s contribution to global governance and its prospects as a stakeholder and shareholder on the global stage.
India and the United Nations
Authors: Bhagavan Manu
Published: December 2015

This chapter discusses India’s association with the United Nations. Guided by the vision of Mahatma Gandhi and Jawaharlal Nehru, the country initially had a highly successful grand strategy guiding its foreign policy that placed that UN at the centre of its diplomatic efforts. Things took a sharp downward turn, however, during the administration of Indira Gandhi, and the relationship has lacked cohesion and meaningful direction ever since. In recent times, India has sought to become a permanent member of the Security Council and has relatedly but unsuccessfully attempted to wield influence, though large questions about its purpose and goals remain. Contemporary crises, though, now make the answers ever more urgent.
India’s Rise
Authors: Khilnani Sunil
Published: December 2015

How should India’s rise be understood in the framework of international relations and a changing global order? This chapter assesses India’s jostle for an advantageous position on the world stage through three sets of lenses: the attempt to voice the civilizational values of a nascent nation; the expressions of the economic and developmental needs of a poor citizenry; and the self-professed aims and pursuits of the interests of a sovereign state. It then outlines some of the challenges in defining India’s international position, and explores possible means through which these can be navigated. In order to optimize the rewards of India’s interactions with the global order, deft management of all three approaches is necessary, enabled by a recognition of the fact that its greatest strength lies in the ability to articulate a democratically validated foreign policy.
Rising or Constrained Power?
Authors: Sridharan Eswaran
Published: December 2015

This chapter analyses India’s prospects as a rising power by asking what kind of power India has the potential to be, given its military, economic, and institutional capacities and the economic and geostrategic constraints it faces. It argues that while sustained high growth is a necessary condition it is not a sufficient condition since economic growth does not necessarily convert smoothly into greater power. Due to such conversion problems India, like some other powers, might not be able to exercise commensurate regional, extra-regional, and global influence as might appear to follow from the revival of sustained high growth and increased economic weight. The more achievable and likely alternative is that of a coalitional or bridging power that can play the role of an effective partner in the security and other spheres to a range of powers, principally to the United States and in the Asia-Pacific and Indian Ocean regions.
Indira Gandhi’s Foreign Policy
Authors: Mansingh Surjit
Published: December 2015

Indira Gandhi’s foreign policy illustrates realist theory in being more attuned to power relations and pragmatic solutions than to moral principles or liberal institutions. Throughout her two tenures in office she manoeuvred successfully to an improved status, especially when dealing with the Bangladesh crisis. Had Mrs Gandhi been a ‘hard realist’ she might have effectively curtailed Pakistan’s capacity to make mischief. She could have used India’s regional dominance to build a South Asian community and formulate a strategy for the adjacent Persian Gulf. She did not do so, and her domestic policy blunders led to her downfall in 1977. On her return to power she did not disrupt India’s beneficial ties with the Soviet Union, tried to mend relations with China, and took steps to strengthen India’s ties with the United States. She hosted several high-level international conferences but her domestic political blunders, as in Punjab, ultimately cost her life.
Dynamics of Interventionism
Authors: Ikeda Sanford
Published: December 2015

The “dynamics of interventionism” refers to the central contribution of Austrian economics to the analysis of government failure. This chapter outlines that contribution in the areas of regulatory dynamics and transfer dynamics and focuses on the role of incentive problems and especially of knowledge problems in driving the mixed economy toward either interventionism or disinterventionism. These dynamics operate in the broad range of politicoeconomic systems that lie between laissez-faire capitalism and collectivist central planning. The chapter examines the rationale for various kinds of interventions, macroeconomic and microeconomic, traces their consequences, and explains why those consequences tend to generate systemic instability in the mixed economy. It also offers an overview of some of the milestones in the development of Austrian political economy.
Spontaneous Order
Authors: D'Amico Daniel
Published: December 2015

This chapter discusses the theoretical substance and history of thought surrounding the theory of spontaneous orders. Whereas significant debate remains regarding the term’s particular origins and appropriate applications, this chapter provides a conceptual framework for categorizing orderly systems according to their agent types and the degree of complexity created by the presence of alternative interests. A substantial and meaningful difference is explained and argued for between the related concepts of emergent order and spontaneous order. While all spontaneous orders possess emergent qualities, the term spontaneous should be reserved to specifically complex human social orders as was originally intended by classical economists and the earliest developers of terminology. This framework is supported by textual references from the intellectual tradition of spontaneous order theorists.
Phenomenological Approaches in the History of Ethnomusicology
Authors: Berger Harris M.
Published: December 2015

Beginning in the late 1970s, ethnomusicologists began to engage with ideas from phenomenology (a movement within continental European philosophy). This article discusses key concepts from phenomenology and explores how ethnomusicologists developed them to address fundamental issues in the study of music and culture—the problem of musical meaning and musical interpretation, the nature of the performance event, and questions of music and being. Tracing the intellectual history of phenomenological ethnomusicology, the article synthesizes findings from research on a broad range of world areas and offers new insights into a variety of topics of interest to contemporary music scholars, including embodiment, self-reflexivity, flow and musical involvement, trance, time and temporality, and research methods. The article closes by discussing the explosion of phenomenological work in ethnomusicology that has occurred in the last seven years and suggests new directions for research, including ethnomusicological inquiry into the politics of music.
Multidimensional Signal Detection Theory
Authors: Ashby F. Gregory , Soto Fabian A.
Published: December 2015

Multidimensional signal detection theory is a multivariate extension of signal detection theory that makes two fundamental assumptions, namely that every mental state is noisy and that every action requires a decision. The most widely studied version is known as general recognition theory (GRT). General recognition theory assumes that the percept on each trial can be modeled as a random sample from a multivariate probability distribution defined over the perceptual space. Decision bounds divide this space into regions that are each associated with a response alternative. General recognition theory rigorously defines and tests a number of important perceptual and cognitive conditions, including perceptual and decisional separability and perceptual independence. General recognition theory has been used to analyze data from identification experiments in two ways: (1) fitting and comparing models that make different assumptions about perceptual and decisional processing, and (2) testing assumptions by computing summary statistics and checking whether these satisfy certain conditions. Much has been learned recently about the neural networks that mediate the perceptual and decisional processing modeled by GRT, and this knowledge can be used to improve the design of experiments where a GRT analysis is anticipated.
Computational Reinforcement Learning
Authors: Gureckis Todd M. , Love Bradley C.
Published: December 2015

Reinforcement learning (RL) refers to the scientific study of how animals and machines adapt their behavior in order to maximize reward. The history of RL research can be traced to early work in psychology on instrumental learning behavior. However, the modern field of RL is a highly interdisciplinary area that lies that the intersection of ideas in computer science, machine learning, psychology, and neuroscience. This chapter summarizes the key mathematical ideas underlying this field including the exploration/exploitation dilemma, temporal-difference (TD) learning, Q-learning, and model-based versus model-free learning. In addition, a broad survey of open questions in psychology and neuroscience are reviewed.
Models of Episodic Memory
Authors: Criss Amy H. , Howard Marc W.
Published: December 2015

Episodic memory refers to memory for specific episodes from one’s life, such as working in the garden yesterday afternoon while enjoying the warm sun and chirping birds. In the laboratory, the study of episodic memory has been dominated by two tasks: single item recognition and recall. In single item recognition, participants are simply presented a cue and asked if they remember it appearing during the event in question (e.g., a specific flower from the garden) and in free recall they are asked to generate all aspects of the event. Models of episodic memory have focused on describing detailed patterns of performance in these and other laboratory tasks believed to be sensitive to episodic memory. This chapter reviews models with a focus on models of recognition with a specific emphasis on REM (Shiffrin & Steyvers, 1997) and models of recall with a focus on TCM (Howard & Kahana, 2002). We conclude that the current state of affairs, with no unified model of multiple memory tasks, is unsatisfactory and offer suggestions for addressing this gap.
Structure and Flexibility in Bayesian Models of Cognition
Authors: Austerweil Joseph L. , Gershman Samuel J. , Griffiths Thomas L.
Published: December 2015

Probability theory forms a natural framework for explaining the impressive success of people at solving many difficult inductive problems, such as learning words and categories, inferring the relevant features of objects, and identifying functional relationships. Probabilistic models of cognition use Bayes’s rule to identify probable structures or representations that could have generated a set of observations, whether the observations are sensory input or the output of other psychological processes. In this chapter we address an important question that arises within this framework: How do people infer representations that are complex enough to faithfully encode the world but not so complex that they “overfit” noise in the data? We discuss nonparametric Bayesian models as a potential answer to this question. To do so, first we present the mathematical background necessary to understand nonparametric Bayesian models. We then delve into nonparametric Bayesian models for three types of hidden structure: clusters, features, and functions. Finally, we conclude with a summary and discussion of open questions for future research.
Neuroimmunophilin Ligand V-10,367 is Neuroprotective after 24-Hour Delayed Administration in a Mouse Model of Diffuse Traumatic Brain Injury
Authors: Kupina Nancy C. , Detloff Megan R. , Dutta Satavisha , Hall Edward D.
Published: December 2015

The authors present two studies that investigate the biochemical and histologic effects of the nonimmunosuppressive neuroimmunophilin (NIMM) ligand V-10,367 in a mouse model of traumatic brain injury (TBI). In study 1, the authors examined the effect of V-10,367 (50 mg/kg x 2 per day, by mouth) on neurofilament M (NFM) protein levels and on α-spectrin breakdown products (SBDPs) when dosed for 2 days, starting 24 hours after TBI and killed on day 3. In study 2, V-10,367 was given for 10 days, starting 24 hours after TBI and the mice killed 6 weeks after TBI, to measure the extent of neurodegeneration (amino CuAg stain). The results in study 1 revealed that V-10,367-treatment significantly increased NFM protein levels in both sham and TBI mice. In addition, V-10,367 attenuated SBDP 150 levels in the cortex, striatum, and hippocampus. The results of study 2 indicated that TBI mice treated with V-10,367 demonstrated significantly less neurodegeneration compared to injured, vehicle-treated mice. In summary, these results suggest that NIMMs may be neuroprotective indirectly through inhibition of calpain-mediated cytoskeletal damage and perhaps via maintenance of neuronal plasticity. In the context of this mouse model of TBI, the therapeutic window for V-10,367's positive effects is at least 24 hours after injury, which, in the case of TBI models, is largely unprecedented for a neuroprotective compound.
Imaging Gene Expression and Endogenous Molecular Processes: Molecular Imaging
Authors: Blasberg Ronald
Published: December 2015

Noninvasive in vivo molecular imaging has developed over the past decade and involves nuclear (positron emission tomography [PET], gamma camera), magnetic resonance, and in vivo optical imaging systems. Most current in vivo molecular imaging strategies are “indirect” and involve the coupling of a “reporter gene” with a complementary “reporter probe.” Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. Reporter gene constructs are driven by upstream promoter/enhancer elements; reporter gene expression can be constitutive, leading to continuous transcription and used to identify the site of transduction and to monitor the level and duration of gene (vector) activity. Alternatively, reporter gene expression can be inducible, leading to controlled gene expression, or reporter genes can function as a “sensor” to monitor the level of endogenous promoters and transcription factors. The development of versatile and sensitive assays that do not require tissue sampling will be of considerable value for monitoring molecular-genetic and cellular processes in animal models of human disease, as well as for studies in human subjects in the future. Noninvasive imaging of molecular-genetic and cellular processes will complement established ex vivo molecular-biologic assays that require tissue sampling, and will provide a spatial as well as a temporal dimension to our understanding of various diseases. Several examples of imaging endogenous biologic processes in animals using reporter constructs, radiolabeled probes, and PET imaging are reviewed (e.g., p53-dependent gene expression, T-cell receptor-dependent activation of T-lymphocytes, and preliminary studies of endogenous HIF-1α expression). Issues related to the translation of noninvasive molecular imaging technology into the clinic are also discussed.
Progesterone Administration during Reperfusion, but not Preischemia Alone, Reduces Injury in Ovariectomized Rats
Authors: Murphy Stephanie J. , Littleton-Kearney Marguerite T. , Hurn Patricia D.
Published: December 2015

Although progesterone is neuroprotective in traumatic brain injury, its efficacy in stroke is unclear. The authors determined whether there are infarction differences after middle cerebral artery occlusion (MCAO) in ovariectomized rats treated acutely with progesterone before MCAO or both pre- and postischemia. Rats received vehicle, 5 (P5), 10 (P10), or 20 (P20) mg/kg progesterone intraperitoneally 30 minutes before MCAO. In another cohort, animals received vehicle or 5 (P5R) mg/kg progesterone intraperitoneally 30 minutes before MCAO, at reperfusion initiation, and at 6-hour reperfusion. Animals underwent 2-hour MCAO by the intraluminal filament technique, followed by 22-hour reperfusion. Cortical (CTX) and caudate-putamen (CP) infarctions were determined by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic and early reperfusion regional cerebral blood flow (CBF) was measured by [14C]-iodoantipyrine quantitative autoradiography in vehicle- or progesterone (5 mg/kg)-treated rats. Cortical infarction (% contralateral CTX) was 31 ± 30% (vehicle), 39 ± 23% (P5), 41 ± 14% (P10), and 28 ± 20% (P20). Caudate-putamen infarction (% contralateral CP) was 45 ± 37% (vehicle), 62 ± 34% (P5), 75 ± 17% (P10), and 52 ± 30% (P20). In vehicle and P5R groups, CTX infarction was 37 ± 20% and *20 ± 17%, respectively (* P < 0.05 from vehicle). In vehicle and P5R groups, CP infarction was 63 ± 26% and 43 ± 29%, respectively. End-ischemic regional CBF and CBF recovery during initial reperfusion was unaffected by progesterone treatment. These data suggest that progesterone administration both before MCAO and during reperfusion decreases ischemic brain injury.
Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum
Authors: Martinez Diana , Slifstein Mark , Broft Allegra , Mawlawi Osama , Hwang Dah-Ren , Huang Yiyun , Cooper Thomas , Kegeles Lawrence , Zarahn Eric , Abi-Dargham Anissa , Haber Suzanne N. , Laruelle Marc
Published: December 2015

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3″) was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (ΔV3″) in limbic (ventral striatum, −15.3 ± 11.8%) and sensorimotor (postcommissural putamen, −16.1 ± 9.6%) regions compared with associative regions (caudate and precommissural putamen, −8.1 ± 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in ΔV3″ between limbic (−17.8 ± 13.8%), sensorimotor (−16.6 ± 9.9%), and associative regions (−7.5 ± 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger ΔV3″ in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.