Are lexical representations graded or discrete?

Most research on mental lexical representations (lemmas) assumes they are discrete and correspond in number to a word's number of distinct meanings. Thus, homophones (bat), whose meanings are unrelated, have separate lemmas for each meaning (one for baseball bat, another for flying bat), whereas polysemes (paper), whose senses are related, have shared lemmas (the same lemma for printer paper and term paper). However, most aspects of cognition are thought to be graded, not discrete; could lemmas be graded too? We conducted a preregistered picture-word interference study with pictures of words whose meanings ranged from unrelated (homophones) to very related (regular polysemes). Whereas semantic competitors to picture names slow picture naming, semantic competitors to non-depicted meanings of homophones facilitate naming, suggesting distinct lemmas for homophones' meanings. We predicted that competitors to non-depicted senses of polysemes would slow naming, as polysemes' depicted and non-depicted senses presumably share a lemma. Crucially, we aimed to examine the transition from facilitation to inhibition: two groupings (where competitors to non-depicted senses led to facilitation for words with two lemmas but inhibition for words with one lemma) would imply that lemmas are indeed discrete. But a transition that varies continuously by sense relatedness would imply that lemmas are graded. Unexpectedly, competitors to non-depicted senses of both homophones and polysemes facilitated naming. Although these results do not indicate whether lemmas are graded or discrete, they do inform a long-standing question on the nature of polysemes, supporting a multiple-lemma (vs. core-lemma) account.

Understanding and Addressing Older Adults' Loneliness: The Social Relationship Expectations Framework.

Loneliness is an experience resulting from a perceived discrepancy between expected and actual social relationships. Although this discrepancy is widely considered the "core mechanism" of loneliness, previous research and interventions have not sufficiently addressed what older adults specifically expect from their social relationships. To address this gap and to help situate research on older adults' loneliness within broader life span developmental theories, we propose a theoretical framework that outlines six key social relationship expectations of older adults based on research from psychology, gerontology, and anthropology: availability of social contacts, receiving care and support, intimacy and understanding, enjoyment and shared interests, generativity and contribution, and being respected and valued. We further argue that a complete understanding of loneliness across the life span requires attention to the powerful impacts of contextual factors (e.g., culture, functional limitations, social network changes) on the expression and fulfillment of older adults' universal and age-specific relationship expectations. The proposed Social Relationship Expectations Framework may fruitfully inform future loneliness research and interventions for a heterogeneous aging population.

Disagreement, justification, and equitable moral judgments: A brief training study.

Although theorists agree that social interactions play a major role in moral development, previous research has not experimentally assessed how specific features of social interactions affect children's moral judgments and reasoning. The current study assessed two features: disagreement and justification. In a brief training phase, children aged 4-5.5 years (N = 129) discussed simple moral scenarios about issues of fairness (how to allocate things between individuals) with a puppet who, in a between-participants factorial design, either agreed or disagreed with the children's ideas and either asked or did not ask the children to justify their ideas. Children then responded to another set of moral scenarios in a test phase that was the same for all children. Children in the "agree and do not justify" baseline condition showed an inflexible equality bias (preferring only equal allocations regardless of context), but children who had experiences of disagreement or experiences of being asked to justify themselves shifted toward making equitable decisions based on common ground norms and values. Furthermore, false belief competence was related to children's decisions and justifications. These findings support the classic Piagetian hypothesis that social interactions are a catalyst of cognitive disequilibrium and moral development.

Genetic syndromes with diabetes: A systematic review.

Previous reviews and clinical guidelines have identified 10-20 genetic syndromes associated with diabetes, but no systematic review has been conducted to date. We provide the first comprehensive catalog for syndromes with diabetes mellitus. We conducted a systematic review of MEDLINE, Embase, CENTRAL, PubMed, OMIM, and Orphanet databases for case reports, case series, and observational studies published between 1946 and January 15, 2020, that described diabetes mellitus in adults and children with monogenic or chromosomal syndromes. Our literature search identified 7,122 studies, of which 160 fulfilled inclusion criteria. Our analysis of these studies found 69 distinct diabetes syndromes. Thirty (43.5%) syndromes included diabetes mellitus as a cardinal clinical feature, and 56 (81.2%) were fully genetically elucidated. Sixty-three syndromes (91.3%) were described more than once in independent case reports, of which 59 (93.7%) demonstrated clinical heterogeneity. Syndromes associated with diabetes mellitus are more numerous and diverse than previously anticipated. While knowledge of the syndromes is limited by their low prevalence, future reviews will be needed as more cases are identified. The genetic etiologies of these syndromes are well elucidated and provide potential avenues for future gene identification efforts, aid in diagnosis and management, gene therapy research, and developing personalized medicine treatments.

Young children conform more to norms than to preferences.

As members of cultural groups, humans continually adhere to social norms and conventions. Researchers have hypothesized that even young children are motivated to act conventionally, but support for this hypothesis has been indirect and open to other interpretations. To further test this hypothesis, we invited 3.5-year-old children (N = 104) to help set up items for a tea party. Children first indicated which items they preferred but then heard an informant (either an adult or another child) endorse other items in terms of either conventional norms or personal preferences. Children conformed (i.e., overrode their own preference to follow the endorsement) more when the endorsements were framed as norms than when they were framed as preferences, and this was the case whether the informant was an adult or another child. The priority of norms even when stated by another child opposes the interpretation that children only conformed in deference to adult authority. These findings suggest that children are motivated to act conventionally, possibly as an adaptation for living in cultural groups.

Why Does Awe Have Prosocial Effects? New Perspectives on Awe and the Small Self.

Awe is an emotional response to stimuli that are perceived to be vast (e.g., tall trees, sunsets) and that defy accommodation by existing mental structures. Curiously, awe has prosocial effects despite often being elicited by nonsocial stimuli. The prevailing explanation for why awe has prosocial effects is that awe reduces attention to self-oriented concerns (i.e., awe makes the self small), thereby making more attention available for other-oriented concerns. However, several questions remain unaddressed by the current formulation of this small-self hypothesis. How are awe researchers defining the self, and what implications might their theory of selfhood have for understanding the "smallness" of the self? Building on theories regarding psychological selfhood, we propose that awe may interact with the self not just in terms of attentional focus but rather at multiple layers of selfhood. We further reinterpret the small self using the notion of the quiet ego from personality psychology. Linking awe to an enriched model of the self provided by personality psychology may be fruitful for explaining a range of phenomena and motivating future research.

Comparative toxicokinetics and tissue distribution of prothioconazole and prothioconazole-desthio in Chinese lizards (Eremias argus) and transcriptional responses of metabolic-related genes.

Prothioconazole (PTC) is a widely used triazolinthione fungicide with low toxicity and short residual period. However, its desulfurization metabolite, prothioconazole-desthio (PTC-d), is more persistent and has higher toxicity in terrestrial animals. In this study, the toxicokinetics (TK) and tissue distribution of PTC and PTC-d in Chinese lizards (Eremias argus) were measured following single oral dose (100 mg kg-1 body weight) treatments. TK parameters indicated that PTC was more rapidly absorbed than PTC-d, as indicated by its shorter time to reach peak concentrations in most tissues. Furthermore, the relative bioavailability of PTC in lizards was lower than that of PTC-d. Compared with PTC, PTC-d preferentially accumulated in lizards, as reflected by longer half-life of PTC-d. During the distribution process, PTC-d generated in vivo was transported from other tissues and was deposited in the skin and tail, where PTC-d may be excreted by exuviation or tail detachment. Preferential enrichment of S-enantiomer of both PTC and PTC-d were observed in all tissues. Hepatic cytochrome P450 gene expression measurement revealed that cyp1a5 and cyp3a28 exhibited the strongest responses in both treatment groups. In addition, the opposite responses of cyp2k4 in different treatment groups may indicate that this enzyme caused differences in the rates of metabolism of the two chemicals. This study compared the TK profile of PTC and its desulfurization metabolite PTC-d in lizards and demonstrated that the desulfurization of PTC could increase its ecological risk due to the higher bioavailability and persistence of PTC-d.

Lying, negligence, or lack of knowledge? Children's intention-based moral reasoning about resource claims.

In a hidden inequality context, resource allocators and resource recipients are unaware that an unknowingly advantaged recipient possesses resources. The present study presented children aged 3-13 years (N = 121) with a hidden inequality vignette involving an accidental transgression in which one resource claimant, who unknowingly possessed more resources than another claimant, made an "unintentional false claim" to resources. This unintentional false claim resulted in depriving another recipient of needed resources. Results revealed that children's ability to accurately identify the claimant's intentions was related to how they evaluated and reasoned about resource claims, a previously understudied aspect of resource allocation contexts. Children's attributions of intentions to the accidental transgressor mediated the relationship between age and evaluations of the accidental transgression and the relationship between age and assignment of punishment to the accidental transgressor. With age, children who negatively evaluated the unintentional false claim shifted from reasoning about lying to a focus on negligence on the part of the unintentional false claimant. This shift reflects an increasing understanding of the accidental transgressor's benign intentions. These findings highlight how mental state knowledge and moral reasoning inform children's comprehension of resource allocation contexts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Brain-to-speech decoding will require linguistic and pragmatic data.

OBJECTIVE: Advances in electrophysiological methods such as electrocorticography (ECoG) have enabled researchers to decode phonemes, syllables, and words from brain activity. The ultimate aspiration underlying these efforts is the development of a brain-machine interface (BMI) that will enable speakers to produce real-time, naturalistic speech. In the effort to create such a device, researchers have typically followed a bottom-up approach whereby low-level units of language (e.g. phonemes, syllables, or letters) are decoded from articulation areas (e.g. premotor cortex) with the aim of assembling these low-level units into words and sentences. APPROACH: In this paper, we recommend that researchers supplement the existing bottom-up approach with a novel top-down approach. According to the top-down proposal, initial decoding of top-down information may facilitate the subsequent decoding of downstream representations by constraining the hypothesis space from which low-level units are selected. MAIN RESULTS: We identify types and sources of top-down information that may crucially inform BMI decoding ecosystems: communicative intentions (e.g. speech acts), situational pragmatics (e.g. recurrent communicative pressures), and formal linguistic data (e.g. syntactic rules and constructions, lexical collocations, speakers' individual speech histories). SIGNIFICANCE: Given the inherently interactive nature of communication, we further propose that BMIs be entrained on neural responses associated with interactive dialogue tasks, as opposed to the typical practice of entraining BMIs with non-interactive presentations of language stimuli.

Integration of Nanomaterials into Three-Dimensional Vertical Architectures.

A novel layer-by-layer three-dimensional (3D) architecture allowing one to expand device fabrication in the vertical direction and integrating functional nanomaterials is presented by emulating civil engineering. The architecture uses SU-8 pillars as structural columns, which support multiple horizontal suspended thin films. The films then serve as platforms for the integration of nanomaterials and nanodevices. Multiple graphene layers suspended across SU-8 pillars with precise control on their vertical spacing are demonstrated. In addition to graphene, silicon nitride films that offer high strength yield and thickness control are also presented. Metallic microstructures, plasmonic nanostructures, semiconducting quantum dots, and monolayer graphene on the suspended films are achieved to prove the capability of integrating functional nanomaterials. This work provides the potential to integrate highly compact micro/nanoscale devices at different vertical levels with high surface density, which allows for more capabilities and functionalities in a single device.

Daily stock index return for the Canadian, UK, and US equity markets, compiled by Morgan Stanley Capital International, obtained from Datastream.

The data presented in this article are related to the research article entitled "Testing and comparing the performance of dynamic variance and correlation models in value-at-risk estimation. North American Journal of Economics and Finance, 40, 116-135. doi:10.1016/j.najef.2017.02.006 (Li, 2017) [1]. Data on daily stock index return for the Canadian, UK, and US equity markets, as compiled by Morgan Stanley Capital International, are provided in this paper. The country indices comprise at least 80% of the stock market capitalization of each country. The data cover the period from January 1, 1990, through September 8, 2016, and include 6963 observations. All stock prices are stated in dollars.

Theory of Mind and Resource Allocation in the Context of Hidden Inequality.

In many situations, children evaluate straightforward resource inequalities as unfair. It remains unclear, however, how children interpret hidden inequalities (i.e., inequalities that are unknown to allocators and/or recipients). Children 3-9-years-old (N = 87) evaluated and attributed intentions to a naïve resource allocator who, while unaware of a hidden inequality, made three hypothetical resource allocations: 1) an unknowingly equitable allocation (which rectified the inequality), 2) an inequitable allocation (which perpetuated the inequality), and 3) an equal allocation (which maintained the inequality). Children without false belief morally-relevant theory of mind (FB MoToM) attributed more positive intentions to the unknowingly equitable allocation than to the inequitable allocation. Children with FB MoToM, however, did not differ in their attributions of intentions to the unknowingly equitable and inequitable allocations, reflecting their knowledge that the naïve allocator was not aware of the hidden inequality. Further, children's attributions of intentions were related to their evaluations of the allocations. These findings underscore the importance of children's social cognitive inferences to their evaluations of resource allocation decisions.

Of Papers and Pens: Polysemes and Homophones in Lexical (mis)Selection.

Every word signifies multiple senses. Many studies using comprehension-based measures suggest that polysemes' senses (e.g., paper as in printer paper or term paper) share lexical representations, whereas homophones' meanings (e.g., pen as in ballpoint pen or pig pen) correspond to distinct lexical representations. Less is known about the lexical representations of polysemes compared to homophones in language production. In this study, speakers named pictures after reading sentence fragments that primed polysemes and homophones either as direct competitors to pictures (i.e., semantic-competitors), or as indirect-competitors to pictures (e.g., polysemous senses of semantic competitors, or homophonous meanings of semantic competitors). Polysemes (e.g., paper) elicited equal numbers of intrusions to picture names (e.g., cardboard) compared to in control conditions whether primed as direct competitors (printer paper) or as indirect-competitors (term paper). This contrasted with the finding that homophones (e.g., pen) elicited more intrusions to picture names (e.g., crayon) compared to in control conditions when primed as direct competitors (ballpoint pen) than when primed as indirect-competitors (pig pen). These results suggest that polysemes, unlike homophones, are stored and retrieved as unified lexical representations.

Mucus barrier-triggered disassembly of siRNA nanocarriers.

The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the mucus, potentiated by the large surface area of the nanocarrier. We have developed a fluorescence activation-based reporter system showing that the interaction between polyanionic mucins and the cationic chitosan/small interfering RNA (siRNA) nanocarriers (polyplexes) results in the disassembly and consequent triggered release of fluorescent siRNA. The quantity of release was found to be dependent on the molar ratio between chitosan amino groups and siRNA phosphate groups (NP ratio) of the polyplexes with a maximal estimated 48.6% release of siRNA over 30 min at NP 60. Furthermore, a microfluidic in vitro model of the gastrointestinal mucus barrier was used to visualize the dynamic interaction between chitosan/siRNA nanocarriers and native purified porcine stomach mucins. We observed strong interactions and aggregations at the mucin-liquid interface, followed by an NP ratio dependent release and consequent diffusion of siRNA across the mucin barrier. This work describes a new model of interaction at the nanocarrier-mucin interface and has important implications for the design and development of nucleic acid-based nanocarrier therapeutics for mucosal disease treatments and also provides insights into nanoscale pathogenic processes.

Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery.

The purpose of this study was to establish and characterize patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mice for utilization in antitumor drug discovery. A total of 96 esophageal squamous cell carcinoma (ESCC) tissues from Chinese patients were transplanted subcutaneously into immunodeficient mice. Histology, EGFR, K-ras, B-raf, and PIK3CA mutations, and HER2 gene amplifications were analyzed in both patient tumors and mouse xenograft tissues using immunohistochemistry, mutant-enriched liquid chip sequencing and fluorescence in situ hybridization assays, respectively. Furthermore, in vivo efficacy studies using five PDECX mice harboring a variety of genetic aberrations were performed using the chemotherapy agents 5-fluorouracil (5-FU) and cisplatin. Thirty-seven PDECX mouse models were successfully established in immunodeficient mice. Pathological analysis revealed similar histological architecture and degrees of differentiation between patient ESCC and xenografted tumors. No mutations were identified in EGFR, K-ras, and B-raf genes in either xenograft models or patient ESCC tissues. In contrast, PIK3CA gene mutations were detected in 12.5% (12/96) ESCC patients and 18.9% (7/37) PDECX models. Interestingly, patient ESCC tissues exhibiting HER2 overexpression or gene amplification were unable to survive in immunodeficient mice. Further analysis showed that PDECX models carrying HER2 2+ expression had no response to 5-FU/cisplatin, compared with HER2-negative models. In conclusion, a panel of PDECX mouse models, which include PIK3CA mutant and HER2-positive models, was established and characterized thus mimicking the current clinical genetic setting of esophageal carcinoma. The sensitivity of HER2-negative ESCC models to chemotherapy supports stratification approaches in the treatment of esophageal carcinoma patients and warrants further investigation of the impact of PI3KCA on treatment response.

Spatial configuration and composition of charge modulates transport into a mucin hydrogel barrier.

The mucus barrier is selectively permeable to a wide variety of molecules, proteins, and cells, and establishes gradients of these particulates to influence the uptake of nutrients, the defense against pathogens, and the delivery of drugs. Despite its importance for health and disease, the criteria that govern transport through the mucus barrier are largely unknown. Studies with uniformly functionalized nanoparticles have provided critical information about the relevance of particle size and net charge for mucus transport. However, these particles lack the detailed spatial arrangements of charge found in natural mucus-interacting substrates, such as certain viruses, which may have important consequences for transport through the mucus barrier. Using a novel, to our knowledge, microfluidic design that enables us to measure real-time transport gradients inside a hydrogel of mucins, the gel-forming glycoprotein component of mucus, we show that two peptides with the same net charge, but different charge arrangements, exhibit fundamentally different transport behaviors. Specifically, we show that certain configurations of positive and negative charges result in enhanced uptake into a mucin barrier, a remarkable effect that is not observed with either charge alone. Moreover, we show that the ionic strength within the mucin barrier strongly influences transport specificity, and that this effect depends on the detailed spatial arrangement of charge. These findings suggest that spatial charge distribution is a critical parameter to modulate transport through mucin-based barriers, and have concrete implications for the prediction of mucosal passage, and the design of drug delivery vehicles with tunable transport properties.

A microfluidic in vitro system for the quantitative study of the stomach mucus barrier function.

In the stomach, a layer of gastric mucus protects the epithelial cells of the stomach wall against damage by the acidic digestive juices in the gastric lumen. Despite considerable research, the biophysical mechanisms for this acid barrier are not understood. We present an in vitro microfluidic tool to characterize the stomach acid barrier, in which purified mucin polymers are "secreted" against an acidic zone on chip, mimicking the in vivo secretion of gastric mucus into an acidic stomach lumen. This device reconstitutes both the H(+) concentration gradient and outward flow environment of the mucus layer in vivo. Our experiments demonstrate that a continuously secreted mucin layer hinders acid diffusion, suggesting novel insights into the barrier role of mucins. More broadly, our system may serve as a platform tool for studying the barrier functions provided by mucus layers in the body and for studying mucus drug interactions.

A microfluidics approach towards high-throughput pathogen removal from blood using margination.

Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.

Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation.

Blood is a highly complex bio-fluid with cellular components making up >40% of the total volume, thus making its analysis challenging and time-consuming. In this work, we introduce a high-throughput size-based separation method for processing diluted blood using inertial microfluidics. The technique takes advantage of the preferential cell focusing in high aspect-ratio microchannels coupled with pinched flow dynamics for isolating low abundance cells from blood. As an application of the developed technique, we demonstrate the isolation of cancer cells (circulating tumor cells (CTCs)) spiked in blood by exploiting the difference in size between CTCs and hematologic cells. The microchannel dimensions and processing parameters were optimized to enable high throughput and high resolution separation, comparable to existing CTC isolation technologies. Results from experiments conducted with MCF-7 cells spiked into whole blood indicate >80% cell recovery with an impressive 3.25 × 10(5) fold enrichment over red blood cells (RBCs) and 1.2 × 10(4) fold enrichment over peripheral blood leukocytes (PBL). In spite of a 20× sample dilution, the fast operating flow rate allows the processing of ∼10(8) cells min(-1) through a single microfluidic device. The device design can be easily customized for isolating other rare cells from blood including peripheral blood leukocytes and fetal nucleated red blood cells by simply varying the 'pinching' width. The advantage of simple label-free separation, combined with the ability to retrieve viable cells post enrichment and minimal sample pre-processing presents numerous applications for use in clinical diagnosis and conducting fundamental studies.

Massively parallel concentration device for multiplexed immunoassays.

A massively parallel nanofluidic concentration device array for multiplexed and high-throughput biomolecule detection is demonstrated. By optimizing the microchannel/nanojunction design and channel conductivity, an array of up to 128 nanofluidic concentration devices were fabricated. Operation of the entire array requires only one inlet and one outlet reservoir, with the application of a single operational voltage bias across them. Concentration efficiencies of the devices were found to be uniform within the array, within 5% error. Alternatively, concentration speed in each channel can be individually tuned by controlling the length of the inlet microchannel and thus controlling the flow rate based on change of the tangential electric field. This allows immuno-binding reactions at different concentration ranges to be performed in parallel. Using multiplexed, successive-concentration enhanced detection in the device, we have shown that the dynamic range and reliability of the immunoassay can be significantly increased.