Transcriptional networks regulate cell fate decisions, which occur at the level of individual cells. However, much of what we know about their structure and function comes from studies averaging measurements over large populations of cells, many of which are functionally heterogeneous. Such studies conceal the variability between cells and so prevent us from determining the nature of heterogeneity at the molecular level. In recent years, many protocols and platforms have been developed that allow the high throughput analysis of gene (...) class='Hi'>expression in single cells, opening the door to a new era of biology. Here, we discuss the need for single cell gene expression analysis to gain deeper insights into the transcriptional control of cell fate decisions, and consider the insights it has provided so far into transcriptional regulatory networks in development. (shrink)

The specific aims of this research study were to examine the differential effect of three different music interventions, namely the interactive music playing therapy, interaction music singing therapy, and receptive music therapy studying the varying latency periods in the response time it took 3-year-old children diagnosed with autism spectrum disorder to elicit the target word vocally; and assess the index of happiness of children with ASD after the implementation of the three music interventions, which can, in turn, be used to (...) influence their overall quality of life through this specific intervention. This study used a combined single-subject research design consisting of delayed multiple baseline across the participants and a multielement design to compare the effects of each music intervention technique targeting the child’s verbal response during playback of a practiced song. Findings demonstrated “singing” to be associated with the lowest latency compared to the other two interventions across participants. Additionally, happiness levels varied from neutral to happy, signifying an overall positive experience during participation in the music applied behavior analysis intervention. (shrink)

Two studies tested whether observers could differentiate between two facets of pride—authentic and hubristic—on the basis of a single prototypical pride nonverbal expression combined with relevant contextual information. In Study 1, participants viewed targets displaying posed pride expressions in response to success, while causal attributions for the success (target's effort vs. ability) and the source of this information (target vs. omniscient narrator conveying objective fact) were varied. Study 2 used a similar method, but attribution information came from both (...) the target and an omniscient narrator; the congruence of these attributions was varied. Across studies, participants tended to label expressions as authentic pride, but were relatively more likely to label them as hubristic pride when (a) contextual information indicated that targets were arrogant and (b) no mitigating information about the target's potential value as a hard-working group member (i.e., that success was actually due to effort) was presented. (shrink)

Work-related satisfaction has critical benefits. To predict work-related satisfaction, we investigated how a counterpart’s expressions of emotional complexity (both positive and negative emotions), positive emotions, and negative emotions influenced a perceiver’s work-related satisfaction during discussions over different work-relevant ideas. We conducted a three-wave coworker survey (N = 529) and an experiment with a confederate as a task partner (N = 378). The results consistently showed significant positive impacts of a counterpart’s emotional complexity and positive emotion expressions on a perceiver’s work-related (...) satisfaction by enhancing the perceiver’s positive emotions and evaluation of the counterpart’s openness. Conversely, a counterpart’s negative emotion expression significantly decreased a perceiver’s work-related satisfaction by reducing perceived counterpart openness. We also did not find a perceiver’s negative emotion as a significant mediator of the associations between the three emotional expressions and work-related satisfaction. Therefore, our investigation highlights similar positive effects of emotional complexity and positive emotion expressions and suggests that an expression of both positive and negative emotions promotes satisfaction by enhancing positive emotions and openness perception. (shrink)

An ideal vision model accounts for behavior and neurophysiology in both naturalistic conditions and designed lab experiments. Unlike psychological theories, artificial neural networks (ANNs) actually perform visual tasks and generate testable predictions for arbitrary inputs. These advantages enable ANNs to engage the entire spectrum of the evidence. Failures of particular models drive progress in a vibrant ANN research program of human vision.

Arrow's account (1951/1963) of the problem of social choice is based upon the assumption that the preferences of each individual in the relevant group are expressible by a single ordering. This paper lifts that assumption and develops a multidimensional generalization of Arrow's framework. I show that, like Arrow's original framework, the multidimensional generalization is affected by an impossibility theorem, highlighting not only the threat of dictatorship of a single individual, but also the threat of dominance of a (...) class='Hi'>single dimension. In particular, even if preferences are single-peaked across individuals within each dimension – a situation called intradimensional single-peakedness – any aggregation procedure satisfying Arrow-type conditions will make one dimension dominant. I introduce lexicographic hierarchies of dimensions as a class of possible aggregation procedures under intradimensional single-peakedness. The interpretation of the results is discussed. (shrink)

A recent single cell mRNA sequencing study by Dueck et al. compares neuronal transcriptomes to the transcriptomes of adipocytes and cardiomyocytes. Single cell ‘omic approaches such as those used by the authors are at the leading edge of molecular and biophysical measurement. Many groups are currently employing single cell sequencing approaches to understand cellular heterogeneity in cancer and during normal development. These single cell approaches also are beginning to address long‐standing questions regarding nervous system diversity. Beyond (...) an innate interest in cataloging cell type diversity in the brain, single cell neuronal diversity has important implications for neurotypic neural circuit function and for neurological disease. Herein, we review the authors’ methods and findings, which most notably include evidence of unique expression profiles in some single neurons. (shrink)

Do children’s single words related to motion and change also encode aspects of environmental events highlighted by Talmy’s motion event analysis? If so, these meanings may predict children’s early verb meanings. Analyzing the kinds of meanings expressed in single “dynamic event words” through motion event semantics yields links between early true verbs in sentences and the semantics encoded in these single words. Dynamic event words reflect the sense of temporal and spatial reversibility established in the late sensorimotor (...) period. We propose that these dynamic meanings provide the semantic foundation for the most common verbs included in early sentences, and thus a bootstrap to full development of the verb repertoire. In this study, we followed the spoken language development of five children. We identified dynamic event words as encoding dynamic change in the following dimensions: spatial direction in relation to self; vertical spatial direction; figure/ground relationships; and temporal event sequences. Verbs continuing the semantics previously identified in dynamic event words occurred early and dominated the verb repertoire through 24 months of age. (shrink)

Focusing on Crispin Wright, I try in Chapter One to show that semantic antirealism cannot stably be combined with either communitarianism or constructivism about meaning. I also argue that the rational tenability of communitarianism is threatened by a powerful argument of Wright's own devising in "What Could Anti-Realism About Ordinary Psychology Possibly Be?" In Chapters Two and Three, I defend the individualist idea that the meaning of an expression in an agent's idiolect is correlative with her understanding of its (...) use. I try to show that individualism, so conceived, is fully compatible with natural-kind externalism and that none of the familiar and widely accepted arguments for social externalism are cogent. I also argue that there is no incompatibility between externalism and self-knowledge in matters of meaning. In Chapters Four and Five, I criticize a transcendental argument developed by Donald Davidson and recently defended by Robert Brandom that a creature cannot properly be credited with language or thought unless it is in communication with at least one other creature. Neither philosopher, I argue, provides a cogent case for the argument's crucial premise that the concept of objectivity is unavailable to a creature outside of a social, linguistic setting. The thesis that meaning is normative has widespread currency in the philosophy of language and does much to motivate the social, deontological approach to meaning taken in Making it Explicit. However, I argue in Chapter Six that central arguments for the thesis rest on confusions about the relation between the concepts of meaning, truth, use and intention. In Chapter Seven, I conclude, by connecting Davidson and Brandom's social account of the concept of objectivity with a certain "non-individualist" theory of perception. Following John McDowell, I argue that the theory renders the empirical contentfulness language and thought unintelligible. (shrink)

In this paper, we investigate the use of event models for automated planning. Event models are the action defining structures used to define a semantics for dynamic epistemic logic. Using event models, two issues in planning can be addressed: Partial observability of the environment and knowledge. In planning, partial observability gives rise to an uncertainty about the world. For single-agent domains, this uncertainty can come from incomplete knowledge of the starting situation and from the nondeterminism of actions. In multi-agent (...) domains, an additional uncertainty arises from the fact that other agents can act in the world, causing changes that are not instigated by the agent itself. For an agent to successfully construct and execute plans in an uncertain environment, the most widely used formalism in the literature on automated planning is “belief states”: sets of different alternatives for the current state of the world. Epistemic logic is a significantly more expressive and theoretically better founded method for representing knowledge and ignorance about the world. Further, epistemic logic allows for planning according to the knowledge (and iterated knowledge) of other agents, allowing the specification of a more complex class of planning domains, than those simply concerned with simple facts about the world. We show how to model multi-agent planning problems using Kripke-models for representing world states, and event models for representing actions. Our mechanism makes use of slight modifications to these concepts, in order to model the internal view of agents, rather than that of an external observer. We define a type of planning domain called epistemic planning domains, a generalisation of classical planning domains, and show how epistemic planning can successfully deal with partial observability, nondeterminism, knowledge and multiple agents. Finally, we show epistemic planning to be decidable in the single-agent case, but only semi-decidable in the multi-agent case. (shrink)

Expression patterns of Antennapedia‐like homeogenes in the mouse embryo show many similarities to those of their homologues in Drosophila. It is argued here that homeogenes may regulate development of the body plan in mouse by mechanisms similar to those used in Drosophila. In particular, they may differentially specify positional address of cell groups within lineage compartments along the body axes. In vertebrates, a single ancestral homeogene cluster has become duplicated to give four separate clusters. Comparisons of homeogene (...) class='Hi'>expression patterns between different clusters of the mouse suggest ways in which duplication has permitted development of a more complex body plan. Cluster duplication may therefore have provided a selective advantage during vertebrate evolution. (shrink)

It is argued that there are ways of individuating the objects of perception without using sortal concepts. The result is an moderate anti-sortalist position on which one can single out objects using demonstrative expressions without knowing exactly what sort of thing those objects are.

BackgroundHappiness is becoming increasingly relevant in recent research, including adolescents. Many studies are using the single-item measure for adolescent happiness, however, its validity is not well known. We aimed to examine the validity of this measure among adolescents in three countries from distinct European regions – Eastern, Southern, and Western.Materials and MethodsThe analysis included data from Health Behaviour in School-aged Children study from three countries and three last surveys. The total sample comprised 47,439 schoolchildren. For validity, the indicators reflecting (...) subjective health, life satisfaction, quality of life, well-being, social support, health complaints, bullying, and self-directed violence were assessed. The calculations were conducted in the total sample and by gender, age, survey year, and country.ResultsThe different indicators of concurrent and convergent validity revealed consistent correlations with happiness, with better well-being, health, and subjective perceptions being related to higher happiness. Meanwhile, health complaints, bullying behaviors, and self-directed violence were related to lower happiness. The subgroup differences were consistent across gender, age groups, countries, and survey rounds. The extent of differences was more expressed among girls.ConclusionThe single item for adolescent happiness measurement features a consistent pattern of validity concerning indicators of concurrent and convergent validity. Higher self-reported happiness is associated with better mental and physical health and well-being, and less expressed negative factors. In addition, among girls the correlations tend to be stronger than boys. (shrink)

This book provides an account of discursive or reason-governed cognition, by synthesizing research in the philosophy of language, the philosophy of mind, and evolutionary anthropology. -/- Using the grasp of a natural language as a model for the autonomous or self-governed rationality of discursive cognition, the author uses a semantics for individual intentions, shared intentions, and normative attitudes as a framework for understanding what it is to be a rational animal. This semantics interprets claims about shared intentions and claims about (...) what people ought and may do as the expression of plans of action that involve taking the points of view of other people within a community. This has important consequences for our understanding of both the natural basis and the social relevance of intentional and normative mental states. In order to distinguish the strong and weak modal force, which characterizes normativity but not shared intentionality, the author argues that a notion of single-minded practical cognition is necessary. This account of single-mindedness is then used to shed light on the autonomy or self-government characteristic of discursive cognition, as manifest in a linguistic community whose members are able to adopt the standpoints of others. -/- Drawing together research in philosophy and the related sciences, the formal account of the semantic content of the claims we use to give expression to shared intentional and normative mental states integrates well with research in cognitive science, evolutionary anthropology, and social psychology concerning the ontogenetic and phylogenetic development of shared intentionality and norm psychology in human beings and other primates. The Single-Minded Animal will appeal to researchers and advanced students working on shared intentionality, normativity, rationality, cognitive science, social and developmental psychology, and evolutionary anthropology. (shrink)

The word ‘equality’ often requires disambiguation, which is provided by context or by an explicit modifier. For each sort of magnitude, there is at least one sense of ‘equals’ with its correlated senses of ‘is greater than’ and ‘is less than’. Given any two magnitudes of the same sort—two line segments, two plane figures, two solids, two time intervals, two temperature intervals, two amounts of money in a single currency, and the like—the one equals the other or the one (...) is greater than the other or the one is greater than the other [sc. in appropriate correlated senses of ‘equals’, ‘is greater than’ and ‘is less than’]. In case there are two or more appropriate senses of ‘equals’, the one intended is often indicated by an adverb. For example, one plane figure may be said to be equal in area to another and, in certain cases, one plane figure may be said to be equal in length to another. Each sense of ‘equality’ is tied to a specific domain and is therefore non-logical. Notice that in every cases ‘equality’ is definable in terms of ‘is greater than’ and also in terms of ‘is less than’ both of which are routinely considered domain specific, non-logical. The word ‘identity’ in the logical sense does not require disambiguation. Moreover, it is not correlated ‘is greater than’ and ‘is less than’. If it is not the case that a certain designated triangle is [sc. is identical to] an otherwise designated triangle, it is not necessary for the one to be greater than or less than the other. Moreover, if two magnitudes are equal then a unit of measure can be chosen and, no matter what unit is chosen, each magnitude is the same multiple of the unit that the other is. But identity does not require units. In this regard, congruence is like identity and unlike equality. In arithmetic, the logical concept of identity is coextensive with the arithmetic concept of equality. The logical concept of identity admits of an analytically adequate definition in terms of logical concepts: given any number x and any number y, x is y iff x has every property that y has. The arithmetical concept of equality admits of an analytically adequate definition in terms of arithmetical concepts: given any number x and any number y, x equals y iff x is neither less than nor greater than y. As Aristotle told us and as Frege retold us, just because one relation is coextensive with another is no reason to conclude that they are one. (shrink)

There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single‐cell molecular variation per se might be crucial for population‐level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of “identical” cells, and this functional diversity facilitates collective behavior that would be inaccessible to a (...) homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population‐level function. We consider several possible methods to further pursue the hypothesis that “variation is function” through the use of comparative analysis and novel experimental techniques. (shrink)

It is a standard feature of the BSA and its variants that systematizations of the world competing to be the best must be expressed in the same language. This paper argues that such single language privileging is problematic because it enhances the objection that the BSA is insufficiently objective, and it breaks the parallel between the BSA and scientific practice by not letting laws and basic kinds be identified/discovered together. A solution to these problems and the ones that prompt (...) single language privileging is proposed in the form of privileging the best system competition. (shrink)

Gadamer’s notion of dialogical truth relies on the claim that self and world “belong together” as aspects of a single, unitary phenomenon, one which is made manifest in language. This view has difficulty, however, accounting for that which is untruthful. To get past this obstacle I suggest that we turn to Nishida’s work, which shows how we can bring self and world together into a kind of harmony such that the cultivation of perception makes possible truthful expression.

Incomplete penetrance and variable expressivity are non‐Mendelian phenomena resulting in the lack of correlation between genotype and phenotype. Not withstanding the diversity in mechanisms, differential expression of homologous alleles within cells manifests as variations in penetrance and expressivity of mutations between individuals of the same genotype. These phenomena are seen most often in dominantly inherited diseases, implying that they are sensitive to concentration of the gene product. In this framework and the advances in understanding the role of microRNA (miRNA) (...) in fine‐tuning gene expression at translational level, we propose miRNA‐mediated regulation as a mechanism for incomplete penetrance and variable expressivity. The presence of miRNA binding sites at 3′ UTR, co‐expression of target gene–miRNA pairs for genes showing incomplete penetrance and variable expressivity derived from available data lend support to our hypothesis. Single nucleotide polymorphisms in the miRNA target site facilitate the implied differential targeting of the transcripts from homologous alleles. (shrink)

Tissues contain complex populations of cells. Like countries, which are comprised of mixed populations of people, tissues are not homogeneous. Gene expression studies that analyze entire populations of cells from tissues as a mixture are blind to this diversity. Thus, critical information is lost when studying samples rich in specialized but diverse cells such as tumors, iPS colonies, or brain tissue. High throughput methods are needed to address, model and understand the constitutive and stochastic differences between individual cells. Here, (...) we describe microfluidics technologies that utilize a combination of molecular biology and miniaturized labs on chips to study gene expression at the single cell level. We discuss how the characterization of the transcriptome of each cell in a sample will open a new field in gene expression analysis, population transcriptomics, that will change the academic and biomedical analysis of complex samples by defining them as quantified populations of single cells. (shrink)

A central feature in contemporary discussions of selfknowledge concerns the epistemic status of mental selfascriptions, such as “I have toothache” or “I believe that p”. The overall project of such discussions is to provide an account of the special status of mental self-ascriptions vis-à-vis other knowledge-claims, including ascriptions of mental states to others. In this respect, two approaches have gained currency in contemporary philosophy. Some authors have focused on the notion of expression, stressing that self-ascriptions are expressions of one’s (...) mental life; whereas others have singled out the notion of transparency as crucial, since self-knowledge involves self-beliefs, and the latter are transparent to one’s available evidence. This critical notice explores one instance of each approach, in order to assess their prospects of success. It concludes that both approaches fail to articulate an account that satisfactorily accommodates the first-person component in the notion of self-knowledge. (shrink)

The temporal single-system (TSS) quantitative approach to Marx's economics is analysed. It is shown that TSS models lack a clear equilibrium concept and a coherent (dis)equilibrium methodology, and that Marx's propositions on value and exploitation are tautologically obtained (i) by constructing a money costs theory of value, where by assumption values are equal to market prices, apart possibly from short-run deviations; and (ii) by arbitrarily assuming that the undefined monetary expression of labour time is positive. In general, the (...) shortcomings of the analytical framework make TSS claims, including the proofs of the law of the tendential fall in the profit rate, unwarranted. (shrink)

The development of each of the four Malpighian tubules of Drosophila during embryogenesis requires a special cell, the tip cell, to achieve full growth. A central question concerns how the tip cell acquires its unique properties within the tubule primordium. In a recent report(1), a sequence of key gene expression events in both the tip cell and its cellular neighbours is described. The results show that there are some significant parallels between tip cell selection and the mechanisms that help (...) select neuroblasts within the developing neuroectoderm. Beyond these similarities between neural development and tip cell selection, the later differentiation of the tip cell shows some intriguing elements of neural cell differentiation. (shrink)

This dissertation investigates the plausibility of metaethical relativism, or more specifically, what I call “moral truth-value relativism”: the idea that the truth of a moral statement or belief depends on who utters or has it, or who assesses it. According to the most prevalent variants of this view in philosophical literature – “standard relativism” – the truth-values are relative to people’s moralities, often understood as some subset of their affective or desirelike attitudes. Standard relativism has two main contenders: absolutism – (...) the view that the truth-values of moral statements and beliefs do not vary in that way – and non-cognitivism – the view that moral judgements do not have truth-values, since they express affective or desire-like attitudes rather than beliefs. Almost the entire dissertation concerns the plausibility of standard relativism in contrast to absolutism. Part 1 examines first the two main arguments for standard relativism: that it accounts for the connection between moral judgements and motivation (chapter 2), and for the prevalence of diversity of moral opinion (chapter 3). Then the most common objection is considered: that it is inconsistent with the existence of genuine moral disagreements (chapter 4). I argue that these arguments are inconclusive. Both relativism and absolutism can account for the features discussed. Part 2 focuses on the fact that different people have different strongly held intuitions about the relative or absolute nature of morality. I argue that given a common methodological approach in philosophy and metaethics, which takes such intuitions as evidence of correct analyses, this difference in intuitions suggests that neither a relativist nor absolutist analysis can be correct for everyone’s moral judgements. I argue that this result holds both given semantic internalism (chapter 6) and given semantic externalism (chapter 7). To get one single analysis of everyone’s moral judgements we would have to abandon the intuitionbased methodology. In chapter 8, however, I argue that we can maintain this methodology if we accept analysis pluralism, the view that different analyses hold for different people’s moral judgements. (shrink)

According to the expressive view of voting, a voter derives expressive utility from casting a vote. We present two possible sources of expressive utility: social interaction with voters having the same political preferences, and interestingness of the election. First, it has been suggested that a voter's expressive utility may increase when there are more voters having the same political preference. We extend this line of study and test the hypothesis that a voter's expressive utility increases as the number of voters (...) having the same political preferences increases in the local community, where interaction occurs more frequently with others than it does with others in distant communities. Second, we propose and test the other hypothesis, that voters’ expressive utility is larger when the election is more interesting. Using 2008 parliamentary election data from Korea, where the election consists of both 245 single-member districts and only one nationwide district for proportional representatives, we find supporting evidence for these two arguments: the turnout rate is significantly and positively related to the share of proportional representation votes for the largest party in each single-member district; the turnout rate is also significantly and positively related to the number of polls for single-member district election conducted by major broadcasting companies, which we use as a proxy variable for interestingness of the election. (shrink)

Rod photoreceptors are among the most sensitive light detectors in nature. They achieve their remarkable sensitivity across a wide variety of species through a number of essential adaptations: a specialized cellular geometry, a G‐protein cascade with an unusually stable receptor molecule, a low‐noise transduction mechanism, a nearly perfect effector enzyme, and highly evolved mechanisms of feedback control and receptor deactivation. Practically any change in protein expression, enzyme activity, or feedback control can be shown to impair photon detection, either by (...) decreasing sensitivity or signal‐to‐noise ratio, or by reducing temporal resolution. Comparison of mammals to amphibians suggests that rod outer‐segment morphology and the molecules and mechanism of transduction may have evolved together to optimize light sensitivity in darkness, which culminates in the extraordinary ability of these cells to respond to single photons at the ultimate limit of visual perception. (shrink)

A speed-accuracy trade-off (SAT) in behavioural decisions is known to occur in a wide range of vertebrate and invertebrate taxa. Accurate decisions often take longer for a given condition, while fast decisions can be inaccurate in some tasks. Speed-accuracy tactics are known to vary consistently among individuals, and show a degree of flexibility during colour discrimination tasks in bees. Such individual flexibility in speed-accuracy tactics is likely to be advantageous for animals exposed to fluctuating environments, such as changes in predation (...) threat. We therefore test whether individual speed-accuracy tactics are fixed or flexible under different levels of predation threat in a model invertebrate, the bumblebee Bombus terrestris. The flexibility of speed-accuracy tactics in a foraging context was tested in the laboratory using a ‘meadow’ of artificial flowers harbouring ‘robotic’ crab spider predators. We found that while the ranking of bees along the speed and accuracy continuums was consistent across two levels of predation threat, there was some flexibility in the tactics used by individual bees – most bees became less accurate at colour discrimination when exposed to predation threat when flower types were rewarding. The relationship between decision speed and accuracy was influenced by predator detectability and the risk associated with making incorrect choices during the colour discrimination task. Predator crypsis resulted in a breakdown in the relationship between speed and accuracy, especially when making an incorrect floral choice incurred a distasteful quinine punishment. No single speed-accuracy tactic was found to be optimal in terms of foraging efficiency under either predation threat situation. However, bees that made faster decisions achieved higher nectar collection rates in predator free situations, while accurate bees achieved higher foraging rates under predation threat. Our findings show that while individual bees remain relatively consistent in terms of whether they place greater emphasis on speed or accuracy under predation threat, they can respond flexibly to the additional time costs of detecting predators. (shrink)

In a paper published in 2006, I argued that the best way of defending something like our current practices of punishing war criminals would be to base the justification of this practice on an expressive theory of punishment. I considered two forms that such a justification could take—a ‘denunciatory’ account, on which the purpose of punishment is supposed to communicate a commitment to certain kinds of standard to individuals other than the criminal and a ‘communicative’ account, on which the purpose (...) of the punishment is to communicate with the perpetrator, and argued for a denunciatory account which I developed at some length. In this paper I would like to reconsider the plausibility of a communicative account. One difficulty that such accounts face is that the punishment of war criminals often involves the inflicting of harsh treatment on them by individuals who are members of states other than their own. On a communicative account this is problematic: on such an account—or at least on the version of it proposed by Duff (2000)—it is essential that those who are punish and those who punish them belong to a single community. When this requirement is not satisfied harsh treatment does not constitute punishment. Duff has argued that the problem can be solved by regarding all human beings as members of a single moral community: here I argue that this suggestion is unsatisfactory and propose an alternative. One consequence of my account is that if it is correct there may limitations on the range of kinds of war criminal that can legitimately be punished by international tribunals. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from (...) the +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

The purpose of this work is to carry out a systematic, detailed analytical study, together with the direct interpretations, as they follow from the analytical expressions obtained, of three basic “experiments” which have been classical examples in our understanding of quantum mechanics. The experiments considered are: the single- and double-slit (-hole) experiments, and the final one, which, in particular, deals with the situation where a particle is “reflected off” the detection screen in the single-slit experiment. Special emphasis is (...) put on pointing out some purely quantum mechanical results, which follow from the analytical expressions, as well as on making a comparison with classical physics. Needless to say, the analysis of such experiments has been extremely important in laying the foundations of quantum physics. (shrink)

Bacterial populations are heterogeneous, which in many cases can provide a selective advantage during changes in environmental conditions. In some instances, heterogeneity exists at the genetic level, in which significant allelic variation occurs within a population seeded by a single cell. In other cases, heterogeneity exists due to phenotypic differences within a clonal, genetically identical population. A variety of mechanisms can drive this latter strategy. Stochastic fluctuations can drive differential gene expression, but heterogeneity in gene expression can (...) also be driven by environmental changes sensed by individual cells residing in distinct locales. Utilizing multiple single cell approaches, workers have started to uncover the extent of heterogeneity within bacterial populations. This review will first describe several examples of phenotypic and genetic heterogeneity, and then discuss many single cell approaches that have recently been applied to define heterogeneity within bacterial populations. (shrink)

COVID-19 outbroke in Wuhan, China, in December 2019 and promptly became a pandemic worldwide, endangering health and life but also causing mild-to-severe psychological distress to lots of people, including healthcare workers. Several studies have already showed a high prevalence of depression, anxiety, and post-traumatic symptoms in HCWs but less is known about the efficacy of psychological interventions for relieving their mental distress. The aims of this study were: to evaluate the psychological adjustment of Italian HCWs during the COVID-19 pandemic; to (...) investigate the efficacy of an expressive writing intervention, based on Pennebaker’s paradigmatic protocol, on their psychological adjustment; to analyze if outcomes of EW vary in function of individual differences. Fifty-five HCWs were randomly assigned to one of two writing conditions: EW or neutral writing. Psychological adjustment was assessed before and after three writing sessions. Participants who received the EW intervention showed higher improvements in ptsd, depression, and global psychopathology symptoms. Improvements in EW group varied in function of age, gender, marital status, and baseline values: young, men, married participants and those who had higher baseline scores showed a higher reduction of psychological distress symptoms while women, single and those who had lower baseline value showed increased social support, and resilience. In conclusion, the EW intervention had positive effects which varied in function of individual differences on HCWs’ psychological health. (shrink)

Advances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This ‘chip‐based’ approach utilizes microscopic arrays of cDNAs printed on glass as high‐density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of >1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a (...) class='Hi'>single hybridization. A two‐color fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass‐produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics. (shrink)

Single-sided deafness (SSD) or profound unilateral hearing loss obligates the only serviceable ear to capture all acoustic information. This loss of binaural function taxes cognitive resources for accurate listening performance, especially under adverse environments or challenging tasks. We hypothesized that adults with SSD would manifest both functional and structural brain plasticity compared to controls with normal binaural hearing. We evaluated functional alterations using magnetoencephalographic imaging (MEGI) of brain activation during performance of a moderately difficult auditory syllable sequence reproduction task (...) and assessed structural integrity using diffusion tensor magnetic resonance imaging (DTI). MEGI showed the SSD cohort to have increased induced oscillations in the theta band over the left superior temporal cortex and decreased induced gamma band oscillations over the frontal and parietal cortices between 175-475 ms following stimulus onset. DTI showed the SSD cohort to have extensive fractional anisotropy reduction in both auditory and non-auditory tracts and regions. Overlaying functional and structural changes revealed by the two imaging techniques demonstrated close registration of cortical areas and white matter tracts that expressed brain plasticity. Hence, complete loss of input from one ear in adulthood triggers both functional and structural alterations to dorsal temporal and frontal-parietal areas. (shrink)

Monoallelic gene expression has played a significant role in the evolution of mammals enabling the expansion of a vast repertoire of olfactory receptor types and providing increased sensitivity and diversity. Monoallelic expression of immune receptor genes has also increased diversity for antigen recognition, while the same mechanism that marks a single allele for preferential rearrangement also provides a distinguishing feature for directing hypermutations. Random monoallelic expression of the X chromosome is necessary to balance gene dosage across (...) sexes. In marsupials only the maternal X chromosome is expressed, while in eutherian mammals the paternal X genes are silenced in the developing placenta and early blastocyst. These examples of epigenetic gene regulation commonly employ asynchrony of replication, the binding of polycomb proteins and antisense RNA, and histone modifications to chromatin structure. The same is true for genomic imprinting which among vertebrates is unique to mammals and represents a special kind of epigenetic modification that is heritable according to parent of origin. Genomic imprinting pervades many aspects of mammalian growth and evolution but in particular has played a significant role in the co‐adaptive evolution of the mother and foetus. (shrink)

Each of the homeotic genes of the bithorax complex of Drosophila defines the identities of more than one body segment. The mechanisms by which this occurs have been elusive. In a recent report, Castelli‐Gair and Akam(1) analyze in detail the control of parasegment 5 and parasegment 6 identities by the bithorax complex gene Ubx. Their results indicate that differences in the spatial and temporal expression patterns of Ubx are critical in determining differences between these parasegments. However, dose effects observed (...) by others indicate that parasegment‐specific differences in the level of Ubx expression are also important. For the other BX‐C genes, parasegment‐specific expression of protein isoforms, or combinatorial control dependent on the expression patterns of other spatially restricted regulators, may also play a role. (shrink)

Rembrandt has been characterized as "the master of the passions of the soul". His painting production has always elicited the viewers' strong emotional responses. Τhese responses raise the question regarding why Rembrandt's work has been singled out as the quintessential example of the expression of emotions both during the 17th century, as well as in recent times. I will try to approach the issue through two different yet interconnected routes. First, I will explore the tools and terms through which (...) the question of the expression of emotions in Rembrandt's oeuvre can be approached. Ancient rhetorical topoi, as well as ideas stemming from Dutch theater writers, drama and art theorists, scholars and art connoisseurs on the rendition of the emotions provide useful points of view. Secondly, I will approach the question by addressing certain stylistic and compositional solutions that Rembrandt suggested, which can be tied to current notions about lifelikeness and the beholder's empathy. Foremost among Rembrandt's aesthetic choices was his handling of light and of paint which accounts for a great deal of unfavorable criticism to his work during the 17th century. I would like to suggest that this handling of light and paint serves as Rembrandt's most important emotive vehicle and furthermore that it introduces us to the idea of wonder and the concept of the sublime in terms of which his depiction of emotions may be understood. Accordingly, I will try to establish an intellectual network in the 17th-century Netherlands for the sublime. (shrink)

We present a cut-free tableau calculus with histories and variables for the EXPTIME-complete multi-modal logic of common knowledge. Our calculus constructs the tableau using only one pass, so proof-search for testing theoremhood of ϕ does not exhibit the worst-case EXPTIME-behaviour for all ϕ as in two-pass methods. Our calculus also does not contain a “finitized ω-rule” so that it detects cyclic branches as soon as they arise rather than by worst-case exponential branching with respect to the size of ϕ. Moreover, (...) by retaining the rooted-tree form from traditional tableaux, our calculus becomes amenable to the vast array of optimisation techniques which have proved essential for “practical” automated reasoning in very expressive description logics. Our calculus forms the basis for developing a uniform framework for the family of all fix-point logics of common knowledge. However, there is still no “free lunch” as, in the worst case, our method exhibits 2EXPTIME-behaviour. A prototype implementation can be found at twb.rsise.anu.edu.au which allows users to test formulae via a simple graphical interface. (shrink)

Of the many proposals for inferring genetic regulatory structure from microarray measurements of mRNA transcript hybridization, several aim to estimate regulatory structure from the associations of gene expression levels measured in repeated samples. The repeated samples may be from a single experimental condition, or from several distinct experimental conditions; they may be “equilibrium” measurements or time series; the associations may be estimated by correlation coefficients or by conditional frequencies (for discretized measurements) or by some other statistic. This paper (...) describes two elementary statistical difficulties for all such procedures, no matter whether based on Bayesian updating, conditional independence testing, or other machine learning procedures such as simulated annealing or neural net pruning. One difficulty obtains if large numbers of cells are aggregated in a measurement of expression levels from a common population of cells; the other obtains if small numbers of cells are aggregated or if samples are separately aggregated over different populations of cells. (shrink)

This article discusses how research on the image-based analysis of facial images has informed this debate by demonstrating that a single representational system for facial identity and facial expression is not only computationally viable, but can simulate existing cognitive data demonstrating apparent dissociable processing of these two facial properties. It discusses the increasing number of cognitive studies that provide support for this view. Neuropsychological case studies of brain-injured patients and provide limited evidence for separate visual routes processing facial (...) identity and facial expression. It deals with neuroimaging studies addressing both facial identity and facial expression processing which shows that the fusiform gyrus contributes to the recognition of both facial properties. Research continues to reinforce the proposal that a common visual framework supports the representation of at least some aspects of facial identity and facial expression. (shrink)

Conversation analysis (CA) of children-adult—interaction in various contexts has become an established field of research. However,child therapyhas received limited attention in CA. In child therapy, the general psychotherapeutic practice of achieving empathy faces particular challenges. In relation to this, our contribution sets out three issues for investigation and analysis: the first one is that practices of achieving empathy must be preceded by efforts aiming to establish which kind of individualized conversation works with this child (Midgley,2006). Psychotherapy process researchers in adult (...) therapy (Stiles et al.,2015) have found that therapists “invent” a new therapy for each patient (Norcross and Wampold,2018). The second issue is that it can be difficult for adults to understand the ways in which children express their conflicts and issues. In particular, play activities in therapy, e.g., with dolls, can open up additional scenarios of interaction. The play scenario can be used to disclose unformulated problems masked in everyday and family interactions. The third issue is how to respect the child's higher degree of vulnerability, compared with adult patients. How is it communicated and dealt with in therapy? We present an interaction analysis of a single case study of the first 20 min of a child therapy session with an adopted girl aged 4 years brought to treatment because of “unexplainable rage.” The session was videotaped; parents granted permission. We analyze this session using an applied version of CA. In our analysis, we describe “doing contrariness,” as a conversational practice producing epistemic and affiliative disruptions, while “avoiding doing contrariness” and “remedying contrariness” are strategies for preserving or restoring the affiliative dimension of a relationship (in child therapy). We show how these practices operate in various modes and how they are used by both parties in our case study to variously aid and impedethe achievement of empathy and understanding. (shrink)

When building personal relationships, it is important to select optimal partners, even based on the first meeting. This study was inspired by the idea that people who smile are considered more trustworthy and attractive. However, this may not always be true in daily life. Previous studies have used a relatively simple method of judging others by presenting a photograph of one person’s face. To move beyond this approach and examine more complex situations, we presented the faces of two people confronted (...) with each other to participants and asked them to judge them from a third-person perspective. Through three experiments, participants were asked to judge which of the two persons was more appropriate for forming alliances, more trustworthy, or more attractive, respectively. In all experiments, images were shown for a short or a long time. In all three experiments, the results showed that participants were more likely to choose persons with happy faces than those with neutral, sad, or angry faces when the image presentation was short. Contrarily, the facial expressions did not affect those judgments when the image presentation was long. Instead, judgments were correlated with personality estimated from the model’s neutral face in a single-person presentation. These results suggest that although facial expressions can affect the judgments of others when observing two-person confrontations from a third-person perspective, when participants have more time to elaborate their judgments, they go beyond expressions. (shrink)

We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive (...) 5V- end dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

In this paper I will discuss certain cases in Japanese and Korean morphosyntax where forms compete to express the same semantic and grammatical information, and attempt to show that in each instance the most economical form is chosen. Presenting an account in terms of Optimality Theory (OT; see Prince and Smolensky (1993), Grimshaw (1995)), I will argue that constraints such as ‘Avoid Word’ and ‘Avoid Affix’ (as in (1)) are motivated as the forces behind the economization. (1) Avoid Word, Avoid (...) Affix. In OT, constraints are violable and ranked. For a given input—in this paper, abstract grammatical and semantic information—the optimal output is the morpho-syntactic expression which best satisfies the constraints in their ranking, even if some constraints are violated. If the constraints in (1) were the only forces on grammatical expression, the optimal output would be silence; but such an output would fail to express any of the information in the input. Hence, there are constraints on what is called ‘Faithfulness’ in OT, constraints which require linguistic material to faithfully express the abstract input information. In the next section of the paper, I discuss cases where a single word competes with a syntactic formation to express the same input information, illustrating a case where ‘Blocking’ extends from morphology into syntax. (shrink)

We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive (...) 5V- end dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

Change blindness—our inability to detect changes in a stimulus—occurs even when the change takes place gradually, without disruption (Simons et al., 2000). Such gradual changes are more difficult to detect than changes that involve a disruption. In this experiment, we extend previous findings to the domain of facial expressions of emotions occurring in the context of a realistic scene. Even with changes occurring in central, highly relevant stimuli such as faces, gradual changes still produced high levels of change blindness: Detection (...) rates were three times lower for gradual changes than for displays involving disruption, with only 15% of the observers perceiving the gradual change within a single trial. However, despite this high rate of change blindness, changes on faces were significantly better detected than color changes occurring on non facial objects in the same scene. (shrink)