Human immunodeficiency virus 1 (HIV-1) is a retrovirus with a ten-kilobase single-stranded RNA genome. HIV-1 must express all of its gene products from a single primary transcript, which undergoes ...alternative splicing to produce diverse protein products that include structural proteins and regulatory factors
. Despite the critical role of alternative splicing, the mechanisms that drive the choice of splice site are poorly understood. Synonymous RNA mutations that lead to severe defects in splicing and viral replication indicate the presence of unknown cis-regulatory elements
. Here we use dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) to investigate the structure of HIV-1 RNA in cells, and develop an algorithm that we name 'detection of RNA folding ensembles using expectation-maximization' (DREEM), which reveals the alternative conformations that are assumed by the same RNA sequence. Contrary to previous models that have analysed population averages
, our results reveal heterogeneous regions of RNA structure across the entire HIV-1 genome. In addition to confirming that in vitro characterized
alternative structures for the HIV-1 Rev responsive element also exist in cells, we discover alternative conformations at critical splice sites that influence the ratio of transcript isoforms. Our simultaneous measurement of splicing and intracellular RNA structure provides evidence for the long-standing hypothesis
that heterogeneity in RNA conformation regulates splice-site use and viral gene expression.
The recent development of telecommunication networks is producing an unprecedented wealth of information and, as a consequence, an increasing interest in analyzing such data both from telecoms and ...from other stakeholders' points of view. In particular, mobile phone datasets offer access to insights into urban dynamics and human activities at an unprecedented scale and level of detail, representing a huge opportunity for research and real-world applications. This article surveys the new ideas and techniques related to the use of telecommunication data for urban sensing. We outline the data that can be collected from telecommunication networks as well as their strengths and weaknesses with a particular focus on urban sensing. We survey existing filtering and processing techniques to extract insights from this data and summarize them to provide recommendations on which datasets and techniques to use for specific urban sensing applications. Finally, we discuss a number of challenges and open research areas currently being faced in this field. We strongly believe the material and recommendations presented here will become increasingly important as mobile phone network datasets are becoming more accessible to the research community.
In this paper, we review some advances made recently in the study of
mobile phone datasets
. This area of research has emerged a decade ago, with the increasing availability of large-scale anonymized ...datasets, and has grown into a stand-alone topic. We survey the contributions made so far on the
social networks
that can be constructed with such data, the study of
personal mobility
,
geographical partitioning
,
urban planning
, and
help towards development
as well as
security and privacy issues
.
The explore-exploit dilemma refers to the challenge of deciding when to forego immediate rewards and explore new opportunities that could lead to greater rewards in the future. While motivational ...neural circuits facilitate learning based on past choices and outcomes, it is unclear whether they also support computations relevant for deciding when to explore. We recorded neural activity in the amygdala and ventral striatum of rhesus macaques as they solved a task that required them to balance novelty-driven exploration with exploitation of what they had already learned. Using a partially observable Markov decision process (POMDP) model to quantify explore-exploit trade-offs, we identified that the ventral striatum and amygdala differ in how they represent the immediate value of exploitative choices and the future value of exploratory choices. These findings show that subcortical motivational circuits are important in guiding explore-exploit decisions.
•Monkeys use sophisticated choice strategies to manage explore-exploit trade-offs•Amygdala and ventral striatum neurons code both exploratory and exploitive choices•Task states and state transitions are encoded in the amygdala and ventral striatum
How do we decide whether to explore a new opportunity or stick with what we know? Costa et al. reveal that neurons in amygdala and ventral striatum, motivational centers of the brain, help to solve this complex reinforcement learning problem.
We study fifteen months of human mobility data for one and a half million individuals and find that human mobility traces are highly unique. In fact, in a dataset where the location of an individual ...is specified hourly, and with a spatial resolution equal to that given by the carrier's antennas, four spatio-temporal points are enough to uniquely identify 95% of the individuals. We coarsen the data spatially and temporally to find a formula for the uniqueness of human mobility traces given their resolution and the available outside information. This formula shows that the uniqueness of mobility traces decays approximately as the 1/10 power of their resolution. Hence, even coarse datasets provide little anonymity. These findings represent fundamental constraints to an individual's privacy and have important implications for the design of frameworks and institutions dedicated to protect the privacy of individuals.
While our understanding of appetitive motivation includes accounts of rich cognitive phenomena, such as choice, sensory-specificity and outcome valuation, the same is not true in aversive processes. ...A highly sophisticated picture has emerged of Pavlovian fear conditioning and extinction, but progress in aversive motivation has been somewhat limited to these fundamental behaviors. Many differences between appetitive and aversive stimuli permit different kinds of analyses; a widely used procedure in appetitive studies that can expand the scope of aversive motivation is Pavlovian-instrumental transfer (PIT). Recently, this motivational transfer effect has been used to examine issues pertaining to sensory-specificity and the nature of defensive control in avoidance learning. Given enduring controversies and unresolved criticisms surrounding avoidance research, PIT offers a valuable, well-controlled procedure with which to similarly probe this form of motivation. Furthermore, while avoidance itself can be criticized as artificial, PIT can be an effective model for how skills learned through avoidance can be practically applied to encounters with threatening or fearful stimuli and stress. Despite sensory-related challenges presented by the limited aversive unconditioned stimuli typically used in research, transfer testing can nevertheless provide valuable information on the psychological nature of this historically controversial phenomenon.
Dynamic population mapping using mobile phone data Deville, Pierre; Linard, Catherine; Martin, Samuel ...
Proceedings of the National Academy of Sciences - PNAS,
11/2014, Letnik:
111, Številka:
45
Journal Article
Recenzirano
Odprti dostop
During the past few decades, technologies such as remote sensing, geographical information systems, and global positioning systems have transformed the way the distribution of human population is ...studied and modeled in space and time. However, the mapping of populations remains constrained by the logistics of censuses and surveys. Consequently, spatially detailed changes across scales of days, weeks, or months, or even year to year, are difficult to assess and limit the application of human population maps in situations in which timely information is required, such as disasters, conflicts, or epidemics. Mobile phones (MPs) now have an extremely high penetration rate across the globe, and analyzing the spatiotemporal distribution of MP calls geolocated to the tower level may overcome many limitations of census-based approaches, provided that the use of MP data is properly assessed and calibrated. Using datasets of more than 1 billion MP call records from Portugal and France, we show how spatially and temporarily explicit estimations of population densities can be produced at national scales, and how these estimates compare with outputs produced using alternative human population mapping methods. We also demonstrate how maps of human population changes can be produced over multiple timescales while preserving the anonymity of MP users. With similar data being collected every day by MP network providers across the world, the prospect of being able to map contemporary and changing human population distributions over relatively short intervals exists, paving the way for new applications and a near real-time understanding of patterns and processes in human geography.
Reinforcement learning (RL) refers to the behavioral process of learning to obtain reward and avoid punishment. An important component of RL is managing explore-exploit tradeoffs, which refers to the ...problem of choosing between exploiting options with known values and exploring unfamiliar options. We examined correlates of this tradeoff, as well as other RL related variables, in orbitofrontal cortex (OFC) while three male monkeys performed a three-armed bandit learning task. During the task, novel choice options periodically replaced familiar options. The values of the novel options were unknown, and the monkeys had to explore them to see if they were better than other currently available options. The identity of the chosen stimulus and the reward outcome were strongly encoded in the responses of single OFC neurons. These two variables define the states and state transitions in our model that are relevant to decision-making. The chosen value of the option and the relative value of exploring that option were encoded at intermediate levels. We also found that OFC value coding was stimulus specific, as opposed to coding value independent of the identity of the option. The location of the option and the value of the current environment were encoded at low levels. Therefore, we found encoding of the variables relevant to learning and managing explore-exploit tradeoffs in OFC. These results are consistent with findings in the ventral striatum and amygdala and show that this monosynaptically connected network plays an important role in learning based on the immediate and future consequences of choices.
Orbitofrontal cortex (OFC) has been implicated in representing the expected values of choices. Here we extend these results and show that OFC also encodes information relevant to managing explore-exploit tradeoffs. Specifically, OFC encodes an exploration bonus, which characterizes the relative value of exploring novel choice options. OFC also strongly encodes the identity of the chosen stimulus, and reward outcomes, which are necessary for computing the value of novel and familiar options.
...Panayi and Killcross revealed that the latter can be disrupted when the manipulation lowering food value also reduces the capacity of a stimulus to retrieve information about its predicted ...outcome. ...Kim et al. demonstrates for the first time how general and specific PIT can be observed in the aversive domain and reveal their reliance on activity in the central amygdala. ...a paper reporting an analysis of computational and representational elements that drive PIT in humans (Degni et al.) established procedures that isolate different forms of the transfer effect. ...this study showed that general motivation effects are obtained under a variety of associative conditions.
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