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The rise in eating disorders, a condition with serious health complications, has been linked to the proliferation of idealized body images on social media platforms. However, the relationship between social media and eating disorders is more complex, with online platforms potentially enabling harmful behaviors by linking people to ``pro-ana'' communities that promote eating disorders. We conceptualize the growth of harmful pro-ana communities as a process of online radicalization. We show that a model of radicalization explains how individuals are driven to conversations about extreme behaviors, like fasting, to achieve the ``thin body'' goal, and how these conversations are validated by pro-ana communities. By facilitating social connections to like-minded others, a shared group identity and emotional support, social media platforms can trap individuals within toxic echo chambers that normalize extreme disordered eating behaviors and other forms of self-harm. Characterizing and quantifying the role of online communities in amplifying harmful conversations will support the development of strategies to mitigate their impact and promote better mental health.

SummaryVarious hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated protein can increase, we studied ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5’s AN1 Zn finger interacts with the Rpt5 ATPase and its C-terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Surprisingly, these C-terminal interactions are sufficient to activate proteolysis. With ZFAND5 bound, entry into the proteasome’s protein translocation channel is wider, and ZFAND5 dissociation causes opening of the 20S gate for substrate entry. Using single-molecular microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.

Sonodynamic therapy (SDT) has aroused great interest for its potential in the treatment of glioblastoma (GBM). SDT relies on tumor-selective accumulation of a sonosensitizer that is activated by ultrasound irradiation (UI) to generate cytotoxic actions. The efficacy of GBM-SDT depends on sufficient sonosensitizer buildup in the tumor, which is, however, seriously hampered by the anatomical and biochemical barriers of the GBM. To overcome this difficulty, we herein propose a delivery strategy of ‘platelets with ultrasound-triggered release property’, which takes advantage of 1) the platelets’ ability to carry cargo and release cargo upon activation, and 2) the ROS-generating property of SDT. To provide proof of concept for the strategy, we first stably loaded platelets with IOPD-Ce6, a nano-formed sonosensitizer consisting of iron oxide nanoparticles coated with polyglycerol and doxorubicin and loaded with chlorine e6. UI of the IOPD-Ce6-loaded platelets (IOPD-Ce6@Plt) elicited ROS generation in the IOPD-Ce6@Plt, which were immediately activated to release IOPD-Ce6 into GBM cells in co-culture which, when subjected to a second time of UI, exhibited pronounced ROS production, DNA injury, viability loss, and cell death in the GBM cells. In the in vivo experiments, mice bearing intracranial GBM grafts exhibited substantial tumor distribution of IOPD-Ce6 following intravenous injection of IOPD-Ce6@Plt and subsequent UI at the tumor site. The GBM grafts then exhibited pronounced cell injury and death after another round of UI of the tumors. Finally, the growth of intra-cranial GBM grafts was significantly slowed when an SDT protocol consisting of an intravenous IOPD-Ce6@Plt injection followed by multiple times of tumor UI had been applied twice to the mice. Our results are strong evidence for the idea that platelets are sound and amenable carriers to deliver sonosensitizers in the GBM in an ultrasound-triggered manner and thus to produce highly targeted and effective SDT of GBM.

Targeting signaling pathways that drive cancer cell migration or proliferation is a common therapeutic approach. A popular experimental technique, the scratch assay, measures the migration and proliferation-driven cell monolayer formation. Scratch assay analyses do not differentiate between migration and proliferation effects and do not attempt to measure dynamic effects. To improve upon these methods, we combine high-throughput scratch assays, continuous video microscopy, and variational system identification (VSI) to infer partial differential equation (PDE) models of cell migration and proliferation. We capture the evolution of cell density fields over time using live cell microscopy and automated image processing. We employ VSI techniques to identify cell density dynamics modeled with first-order kinetics of advection-diffusion-reaction systems. We present a comparison of our methods to results obtained using traditional inference approaches on previously analyzed 1-dimensional scratch assay data. We demonstrate the application of this pipeline on high throughput 2-dimensional scratch assays and find that decreasing serum levels can decrease random cell migration by approximately 20%. Our integrated experimental and computational pipeline can be adapted for automatically quantifying the effect of biological perturbations on cell migration and proliferation in various cell lines.

The current study used an attentional blink (AB) paradigm to test how grouping influences the initial selection and the subsequent short-term memory consolidation of a target. On a given trial, two red Kanizsa-type targets (T1, T2) with varying grouping strength were embedded in a rapid serial visual presentation stream of irrelevant distractors.

Visual working memory (VWM) is typically considered to represent complete objects, that is, separate parts of an object are maintained as bound objects. Yet, it remains unclear whether and how the features of disparate parts are integrated into a whole-object memory representation. Using a change detection paradigm, the present study investigated whether VWM performance varies as a function of grouping strength for features that either determine the grouped object (orientation) or which are not directly grouping-relevant (color). Our results showed a large grouping benefit for grouping-relevant orientation features and additionally, a smaller, but still reliable benefit for grouping-irrelevant color features when both were potentially task-relevant. By contrast, when color was the only task-relevant feature, no grouping benefit from the orientation feature was revealed both under lower or relatively high demands for precision.

Does multisensory distractor-target context learning enhance visual search over and above unisensory learning? To address this, we had participants perform a visual search task under both uni- and multisensory conditions. Search arrays consisted of one Gabor target that differed from three homogeneous distractors in orientation; participants had to discriminate the target’s orientation. In the multisensory session, additional tactile (vibration-pattern) stimulation was delivered to two fingers of each hand, with the odd-one-out tactile target and the distractors co-located with the corresponding visual items in half the trials; the other half presented the visual array only. In both sessions, the visual target was embedded within identical (repeated) spatial arrangements of distractors in half of the trials. The results revealed faster response times to targets in repeated versus non-repeated arrays, evidencing ‘contextual cueing’. This effect was enhanced in the multisensory session—importantly, even when the visual arrays presented without concurrent tactile stimulation. Drift–diffusion modeling confirmed that contextual cueing increased the rate at which task-relevant information was accumulated, as well as decreasing the amount of evidence required for a response decision. Importantly, multisensory learning selectively enhanced the evidence-accumulation rate, expediting target detection even when the context memories were triggered by visual stimuli alone.

Title Evaluation of Factors Affecting the Decision-Making Process of Sneaker Purchase among Chinese Post 90s Consumers. Background Sneakers have become an essential part of the younger generation's wardrobe in today's society, reflecting the millennial drive for comfort and leisure. It ultimately portrays a playful and stylish image among post-90s consumers. In the colossal sneaker market, various factors influence consumers' purchasing decisions. Purpose The study's objective is to analyse the factors affecting the decision making process of Chinese post-90s consumers in purchasing sneakers. It explores factors behind consumers' purchasing behaviors that are special and different from those of consumers in other parts of the world in the vast market of China. The study focuses on strengthening the knowledge on the topic. Additionally, the study will provide information on what drives China's post-90s consumers' buying decisions on sneakers. Marketers will be able to analyse the factors and come up with services or sneaker products that satisfy consumers. The paper will summarize the factors that influence consumers' purchasing decisions of sneakers by combining literature surveys and interviews. Method Semi-structured interviews with 12 respondents were conducted. Through the analysis and coding of the interview, the key influencing factors in consumer decision-making are identified. The literature review analysed the five steps of consumer decision-making progress. Conclusion: Consumers make purchase decisions primarily based on their liking for products. Marketers should reasonably position the product range that consumers like and recommend them. Friends' recommendations and discussions influence consumers' purchasing behavior. Establishing good product experience and after-sales service in the marketing process affects brand reputation.

BackgroundHand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population.MethodsA total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing.ResultsWe observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium, were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD.ConclusionsThis study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora.

Additional file 4: Table S4. Oligonucleotide sequences in this study.

Additional file 2: Table S2. Information of CRC patients collected in tissue microarray of metastasis.

Additional file 7: Table S7. Primer sequences for the miR-200 family members/CDH1 in ChIP assay.

Additional file 1: Table S1. Information of CRC patients collected for clinical studies.

Illusory figures demonstrate the visual system's ability to integrate disparate parts into coherent wholes. We probed this object integration process by either presenting an integrated diamond shape or a comparable ungrouped configuration that did not render a complete object. Two tasks were used that either required localization of a target dot (relative to the presented configuration) or discrimination of the dot's luminance. The results showed that only when the configuration was task relevant (in the localization task), performance benefited from the presentation of an integrated object. Concurrent functional magnetic resonance imaging was performed and analyzed using dynamic causal modeling to investigate the (causal) relationship between regions that are associated with illusory figure completion. We found object‐specific feedback connections between the lateral occipital cortex (LOC) and early visual cortex (V1/V2). These modulatory connections persisted across task demands and hemispheres. Our results thus provide direct evidence that interactions between mid‐level and early visual processing regions engage in illusory figure perception. These data suggest that LOC first integrates inputs from multiple neurons in lower‐level cortices, generating a global shape representation while more fine‐graded object details are then determined via feedback to early visual areas, independently of the current task demands., The visual system has a remarkable ability to integrate disparate parts into coherent whole objects, as illustrated, for example, by the perception of illusory figures. This study investigates connectivity patterns associated with illusory figures and provides direct evidence that the formation of completed objects relies on feedback connections from mid‐level to early visual processing regions: LOC first generates a global shape representation while more fine‐graded object details are then determined via (back‐) projections to early visual areas, independently of the current task demands.

Additional file 5: Table S5. Antibodies used for ChIP, western blot, IHC and IF assays in this study.

Additional file 3: Table S3. Information of CRC patients collected in tissue microarray of survival.

Additional file 10. Supplementary methods.

Additional file 9: Table S9. Primers used for construction of plasmids in CRISPR-Cas9 assay.

Additional file 6: Table S6. Primer sequences for the 36 miRNAs in qRT-PCR assay of CRC cells.

Additional file 8: Table S8. Primers used for qRT-PCR analysis in this study.

This work presented a new drone-based face detection dataset Drone LAMS in order to solve issues of low performance of drone-based face detection in scenarios such as large angles which was a predominant working condition when a drone flies high. The proposed dataset captured images from 261 videos with over 43k annotations and 4.0k images with pitch or yaw angle in the range of -90{\deg} to 90{\deg}. Drone LAMS showed significant improvement over currently available drone-based face detection datasets in terms of detection performance, especially with large pitch and yaw angle. Detailed analysis of how key factors, such as duplication rate, annotation method, etc., impact dataset performance was also provided to facilitate further usage of a drone on face detection., Comment: 10 pages, 6 figures,conference or other essential info

Human papillomavirus (HPV) type 16 is the most common type implicated as the etiological agent that causes cervical cancer. The marketed prophylactic vaccines against HPV infection are composed of virus-like particles (VLPs) assembled from the recombinant major capsid protein L1. Elicitation of functional and neutralizing antibodies by vaccination is the mode of action by which the vaccines prevent the viral infection. In this study, a panel of murine mAbs against HPV16 L1 were generated and comprehensively characterized with respect to their mapping to the epitope spectrum on the viral capsid. These mAbs were categorized into five epitope bins by two different methods based on the pairwise cross-inhibition and competition with human polyclonal antibodies. In addition, a preliminary demonstration of the spatial relationship of the epitopes recognized by these mAbs was performed using a cross-blocking assay with a well-characterized human mAb, 26D1. Interestingly, two mAbs recognizing different epitopes were found to act synergistically in the pseudovirion-based neutralization assay (PBNA). To facilitate cross-lab and cross-study comparison, the international standard (IS) serum 05/134 was used to calibrate the mAbs as well as the human serum samples from the HPV16/18 vaccine recipients. The neutralizing mAbs, particularly those that recognizing immunodominant epitopes, would be useful in developing epitope-specific assays for monitoring the vaccine production process and for serological assessment.

Thimerosal has been widely used as a preservative in human vaccines for decades. Thimerosal, a thiol capping agent with ethyl mercury being the active degradant, could have impacts on the vaccine potency due to potential thiol modification. The effects on the antigenicity and immunogenicity of human papillomavirus (HPV) virus-like particles (VLPs) in the presence of thimerosal was studied. In general, reduced binding activity was observed between HPV antigens and monoclonal antibodies (mAbs) upon thimerosal treatment, accompanied by reduced protein conformational stability. The immunogenicity of a pentavalent vaccine formulation (HPV6, HPV11, HPV16, HPV18 and hepatitis E virus) with or without thimerosal was studied in mice. The functional antibody titres, as well as the binding titres, were determined, showing a substantial decrease for vaccine formulations containing thimerosal for HPV16/18. Similarly, epitope-specific competition assays using specific and functional mAbs as tracers also showed a significant reduction in immunogenicity for HPV16/18 in the presence of thimerosal. Structural alterations in the capsid protein for HPV18 were observed with cryo-electron microscopy and 3-dimensional reconstruction in the comparative structural analysis. The results should alert scientists in formulation development field on the choice for vaccine preservatives, in particular for thiol-containing antigens.

Completion of a partially occluded object requires that a representation of the whole is constructed based on the information provided by the physically specified parts of the stimulus. Such processes of amodal completion rely on the generation and maintenance of a mental image that renders the completed object in visual working memory (VWM). The present study examined this relationship between VWM storage and processes of object completion. We recorded event-related potentials to track VWM maintenance by means of the contralateral delay activity (CDA) during a change detection task in which composite objects (notched shapes abutting an occluding shape) to be memorized were primed to induce either a globally completed object or a noncompleted, mosaic representation.\ud The results revealed an effect of completion in VWM despite physically identical visual input: change detection was more accurate for completed compared with mosaic representations when observers were required to memorize two objects, and these differences were reduced with four memorized items. At the electrophysiological level, globally completed (vs. mosaic) objects gave rise to a corresponding increase in CDA amplitudes. These results indicate that although incorporating the occluded portions of the presented shapes requires mnemonic resources, the complete object representations thus formed in VWM improve change detection performance by providing a more simple, regular shape. Overall, these findings demonstrate that mechanisms of object completion modulate VWM, with the memory load being determined by the structured representations of the memorized stimuli.

Perceived parental rejection in childhood is known to be associated panculturally with at least 10 specific personality dispositions, including anxiety, insecurity, anger, impaired self-esteem, emotional unresponsiveness, negative worldview, and rejection sensitivity—among others. Because of these negative personality dispositions, interpersonal acceptance-rejection theory (IPARTheory) predicts that adults’ remembrances of parental rejection in childhood are likely to be associated with adults’ fear of intimacy, as mediated by adults’ psychological maladjustment and relationship anxiety. The theory also predicts that these associations will not vary significantly by gender, ethnicity/culture, or other such defining conditions. To test these predictions a sample of 3, 483 young adults in 13 nations responded to the mother and father versions of the Adult Parental Acceptance-Rejection Questionnaire (short forms), Adult Personality Assessment Questionnaire (short form), the Interpersonal Relationship Anxiety Questionnaire, the Fear of Intimacy Scale, and the Revised Personal Information Form. Results of SEM analyses confirmed the prediction in all 13 countries and across both genders that adults’ remembrances of both maternal and paternal rejection independently predict adults’ psychological maladjustment and relationship anxiety, which in turn predict fear of intimacy. Psychological maladjustment partially mediated the association between remembered maternal and paternal rejection, and adults’ fear of intimacy.

Ultra-dense networking is widely accepted as a promising enabling technology to realize high power and spectrum efficient communications in future 5G communication systems. Although joint resource allocation schemes promise huge performance improvement at the cost of cooperation among base stations, the large numbers of user equipment and base station make jointly optimizing the available resource very challenging and even prohibitive. How to decompose the resource allocation problem is a critical issue. In this paper, we exploit factor graphs to design a distributed resource allocation algorithm for ultra dense networks, which consists of power allocation, subcarrier allocation and cell association. The proposed factor graph based distributed algorithm can decompose the joint optimization problem of resource allocation into a series of low complexity subproblems with much lower dimensionality, and the original optimization problem can be efficiently solved via solving these subproblems iteratively. In addition, based on the proposed algorithm the amounts of exchanging information overhead between the resulting subprob-lems are also reduced. The proposed distributed algorithm can be understood as solving largely dimensional optimization problem in a soft manner, which is much preferred in practical scenarios. Finally,the performance of the proposed low complexity distributed algorithm is evaluated by several numerical results.

The factors affecting the economy efficiency of rail grinding and their interrelation are researched. Based on the management theory of life-cycle cost, the model of analyzing rail grinding parameters is established, the calculation method is determined, and minimizing the rail life-cycle cost is regarded as optimization objective for the optimal analysis of grinding factor. The results prove that with certain parameters (grinding interval and mental removal), the total present value of rail cost tends to decrease firstly and then increase with the increase of rail service life. With the increase of the grinding interval, the total present value of rail cost also tends to decrease firstly and then increase, and there is an extreme point in the variation tendency. In the economic cost of rail service life, rail replacement and waste of railway taking-up cost are two of the biggest parts. Therefore, reasonable rail maintenance strategy plays a significant role in reducing life-cycle cost.

This study assesses interpersonal acceptance-rejection theory’s (IPARTheory’s) prediction that adults’ (both men’s and women’s) remembrances of parental (both maternal and paternal) rejection in childhood are likely to be associated with adults’ fear of intimacy, as mediated by adults’ psychological maladjustment and relationship anxiety. The study also assesses the prediction that these associations will not vary significantly by gender, ethnicity, language, culture, or other such defining conditions. To test these predictions a sample of 3,483 young adults in 13 nations responded to the mother and father versions of the Adult Parental Acceptance-Rejection Questionnaire (short forms), Adult Personality Assessment Questionnaire (short form), the Interpersonal Relationship Anxiety Questionnaire, the Fear of Intimacy Scale, and the Revised Personal Information Form. Results of multigroup analyses showed that adults’ remembrances of both maternal and paternal rejection in childhood independently predicted men’s and women’s fear of intimacy in all 13 countries. However, remembered maternal rejection was a significantly stronger predictor of adults’ fear of intimacy than was remembered paternal rejection. Results also confirmed the prediction in all 13 countries and across both genders that both maternal and paternal rejection independently predicted adults’ psychological maladjustment and relationship anxiety, which in turn predicted fear of intimacy. In addition, psychological maladjustment partially mediated the relation between remembrances of maternal and paternal rejection, and adults’ fear of intimacy in all 13 countries and both genders. © 2019 SAGE Publications.