Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model

Yes‐associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030‐BrM3(K‐rasG12C mutation) and PC9‐BrM3 (EGFRΔexon19 mutation) had a significantly decreased p‐YAP(S127)/YAP ratio compared to parental H2030 (K‐rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < .05). H2030‐BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030‐BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030‐BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA‐transfected H2030‐BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030‐BrM3 cell brain metastasis in a murine model.
iFridge: an intelligent fridge for food management based on RFID technology

It is a tedious task to search and locate a specific food from a massive number of foods arbitrarily placed in a fridge. In this paper, we develop iFridge, an intelligent system which allows the user to effectively manage and accurately locate the foods stored inside the fridge. By leveraging the RFID technology, iFridge is able to automatically collect the food information, perceive the user's activities and locate the specified foods. We develop a smart application "cooking recipe recommendation" by sensing the user's daily eating habits. Moreover, by specifying those foods with roughly known locations as anchor nodes, we are able to locate the specified food by using cluster analysis.
A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life*

The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction.
Studies on nylon 6/clay nanocomposites by melt-intercalation process

The preparation of nylon 6/clay nanocomposites by a melt-intercalation process is proposed. X-ray diffraction and DSC results show that the crystal structure and crystallization behaviors of the nanocomposites are different from those of nylon 6. Mechanical and thermal testing shows that the properties of the nanocomposites are superior to nylon 6 in terms of the heat-distortion temperature, strength, and modulus without sacrificing their impact strength. This is due to the nanoscale effects and the strong interaction between the nylon 6 matrix and the clay interface, as revealed by X-ray diffraction, transmission electron microscopy, and Molau testing. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1133–1138, 1999
Unhealthy Alcohol Use, HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C

Aim To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values. Conclusions Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations
Role of sequence evolution and conformational dynamics in the substrate specificity and oligomerization mode of thymidylate kinases

Thymidylate kinase (TMK) is a key enzyme for the synthesis of DNA, making it an important target for the development of anticancer, antibacterial, and antiparasitic drugs. TMK homologs exhibit significant variations in sequence, residue conformation, substrate specificity, and oligomerization mode. However, the influence of sequence evolution and conformational dynamics on its quaternary structure and function has not been studied before. Based on extensive sequence and structure analyses, our study detected several non-conserved residues which are linked by co-evolution and are implicated in the observed variations in flexibility, oligomeric assembly, and substrate specificity among the homologs. These lead to differences in the pattern of interactions at the active site in TMKs of different specificity. The method was further tested on TMK from Sulfolobus tokodaii (StTMK) which has substantial differences in sequence and structure compared to other TMKs. Our analyses pointed to a more flexible dTMP-binding site in StTMK compared to the other homologs. Binding assays proved that the protein can accommodate both purine and pyrimidine nucleotides at the dTMP binding site with comparable affinity. Additionally, the residues responsible for the narrow specificity of Brugia malayi TMK, whose three-dimensional structure is unavailable, were detected. Our study provides a residue-level understanding of the differences observed among TMK homologs in previous experiments. It also illustrates the correlation among sequence evolution, conformational dynamics, oligomerization mode, and substrate recognition in TMKs and detects co-evolving residues that affect binding, which should be taken into account while designing novel inhibitors.
Experiences of mental health nursing staff working with voice hearers in an acute setting: An interpretive phenomenological approach

WHAT IS KNOWN ON THE SUBJECT? : Community mental health staff and their service users have reported mixed views on the importance of talking about the content of voices. Community staff have reported feeling that they do not have the skills to explore voice content and worry about making things worse. Voice hearers experiencing extreme distress due to the content of their voices can access support through acute inpatient mental health services. No previous studies have focused on the experiences of staff who nurse voice hearers at a time of acute distress. WHAT DOES THIS STUDY ADD TO EXISTING KNOWLEDGE? : MHNs and HSWs working with voice hearers in acute distress report feeling powerless and helpless, as they feel that they cannot lessen the distress experienced by the voice hearer. Despite these difficult feelings, staff report finding ways of coping, including using structured tools to help make sense of their service users' voice-hearing experiences and accessing reflective practice forums. WHAT ARE THE IMPLICATIONS FOR PRACTICE? : Due to the current context of increased acuity and limited resources in acute services, there may be a need to further protect time for staff to access reflective practice groups and supervision forums to help them manage the difficult feelings arising from their work with voice hearers. ABSTRACT Introduction Mental health nursing (MHN) staff in acute settings work with voice hearers at times of crises when they experience high levels of distress. Previous research has focused on community mental health staff's experiences and their service users views on exploring the content of voices. No studies have explored this from an acute mental health service perspective. Aim This study therefore sought to explore the experiences of staff working with voice hearers in an acute mental health service. Method Due to the exploratory nature of the research, a qualitative design was chosen. Three MHNs and five healthcare support workers (HSWs) were interviewed. The data were analysed using Interpretative Phenomenological Analysis. Results A group analysis elicited three master themes: "It's quite scary really, not unlike a horror movie;" "I can only influence what's in front of me;" and "Just chipping away". Discussion Staff working with voice hearers in acute settings experience feelings of powerlessness and helplessness, as they feel unable to reduce the distress experienced by voice hearers in their care. Staff employ coping strategies to help manage these difficult feelings, including using structured tools in their work with voice hearers and attending reflective practice forums. Implications for Practice Acute mental health services may need to protect time for staff to access regular reflective practice and other supervision forums to help manage their feelings of powerlessness and helplessness arising from their work with voice hearers.
A life uncertain – My baby’s vulnerability: Mothers’ lived experience of connection with their preterm infants in a Botswana neonatal intensive care unit

Background Preterm and low–birth weight infants are often separated from their mothers when admitted to neonatal units for stabilisation of body temperature and technological support. Objectives The aim of the study was to explore and describe the lived experiences of mothers regarding care of their hospitalised preterm infants in a neonatal unit in a public hospital in Gaborone, Botswana. Method This study utilised a qualitative exploratory and descriptive phenomenological study design. Mothers of hospitalised preterm infants were purposefully selected, with whom there was extensive engagement. Two in-depth interviews were conducted with each participant (P). Results Mothers were shocked by the sudden birth of a preterm infant and found the neonatal environment intimidating. This increased their fear and anxiety and delayed development of a relationship with their infants. Support from staff, other mothers in the neonatal unit and family members enabled the mothers to overcome their fear and to develop an emotional connection with their infants. Conclusion On-going supportive communication with the mothers by healthcare professionals promotes their confidence and competence in caring for their preterm infants, which in turn promotes mother–infant attachment.
Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs. Importantly, HA acted as a signaling ligand of its cognate receptor RHAMM for intracellular signaling activation underlying invasiveness of GBM cells. Taken together, our study suggests that tMSLCs contribute to HA-rich proinvasive ECM microenvironment in GBM.
Exogenous IL-33 overcomes T cell tolerance in murine acute myeloid leukemia

Emerging studies suggest that dominant peripheral tolerance is a major mechanism of immune escape in disseminated leukemia. Using an established murine acute myeloid leukemia (AML) model, we here show that systemic administration of recombinant IL-33 dramatically inhibits the leukemia growth and prolongs the survival of leukemia-bearing mice in a CD8+ T cell dependent manner. Exogenous IL-33 treatment enhanced anti-leukemia activity by increasing the expansion and IFN-γ production of leukemia-reactive CD8+ T cells. Moreover, IL-33 promoted dendritic cell (DC) maturation and activation in favor of its cross presentation ability to evoke a vigorous anti-leukemia immune response. Finally, we found that the combination of PD-1 blockade with IL-33 further prolonged the survival, with half of the mice achieving complete regression. Our data establish a role of exogenous IL-33 in reversing T cell tolerance, and suggest its potential clinical implication into leukemia immunotherapy.
A Mediation Model for Ideas of Reference

Ideas of reference are common in human beings, but they are frequent in certain psychopathological disorders, mainly those concerning the psychotic spectrum. The purpose of this study was to attempt to construct a model predicting the appearance of ideas of reference and to test the relationship of personality (based on the Gray model), emotional, and self-consciousness variables. Five-hundred and seventy-four participants (287 patients with several different psychopathological diagnoses) filled in the Referential Thinking Scale (REF), the GHQ-28, the Self-Consciousness Scale (SCS-R), and the SPSRQ Scale. The resulting model found full mediation of sensitivity to punishment, sensitivity to reward, depression, and public self-consciousness between anxiety and ideas of reference, regardless of the group they were in (patients vs. nonpatients). This result, based on the appearance of anxiety symptomatology, explains 43% of the variance in scores, showing the presence of ideas of reference and therefore enables prediction of a set of vulnerabilities (established with self-reports) which could lead to a psychological state of high general pathological risk and proneness to psychosis in particular.
First-passage time approach to controlling noise in the timing of intracellular events

Significance Understanding how randomness in the timing of intracellular events is buffered has important consequences for diverse cellular processes, where precision is required for proper functioning. To investigate event timing in noisy biochemical systems, we develop a first-passage time framework in which an event is triggered when a regulatory protein accumulates up to a critical level. Formulas quantifying event-timing fluctuations in stochastic models of protein synthesis with feedback regulation are developed. Formulas shed counterintuitive insights into regulatory mechanisms essential for scheduling an event at a precise time with minimal fluctuations. These results uncover various features in the biochemical pathways used by phages to lyse individually infected bacterial cells at an optimal time, despite stochastic expression of lysis proteins. In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is triggered when the level of a protein crosses a critical threshold for the first time. Analytical calculations are performed for the first-passage time distribution in stochastic models of gene expression. Derivation of these formulas motivates an interesting question: Is there an optimal feedback strategy to regulate the synthesis of a protein to ensure that an event will occur at a precise time, while minimizing deviations or noise about the mean? Counterintuitively, results show that for a stable long-lived protein, the optimal strategy is to express the protein at a constant rate without any feedback regulation, and any form of feedback (positive, negative, or any combination of them) will always amplify noise in event timing. In contrast, a positive feedback mechanism provides the highest precision in timing for an unstable protein. These theoretical results explain recent experimental observations of single-cell lysis times in bacteriophage λ. Here, lysis of an infected bacterial cell is orchestrated by the expression and accumulation of a stable λ protein up to a threshold, and precision in timing is achieved via feedforward rather than feedback control. Our results have broad implications for diverse cellular processes that rely on precise temporal triggering of events.
Mapping the distribution of language related genes FoxP1, FoxP2, and CntnaP2 in the brains of vocal learning bat species

Genes including FOXP2, FOXP1, and CNTNAP2, have been implicated in human speech and language phenotypes, pointing to a role in the development of normal language‐related circuitry in the brain. Although speech and language are unique to humans a comparative approach is possible by addressing language‐relevant traits in animal systems. One such trait, vocal learning, represents an essential component of human spoken language, and is shared by cetaceans, pinnipeds, elephants, some birds and bats. Given their vocal learning abilities, gregarious nature, and reliance on vocalizations for social communication and navigation, bats represent an intriguing mammalian system in which to explore language‐relevant genes. We used immunohistochemistry to detail the distribution of FoxP2, FoxP1, and Cntnap2 proteins, accompanied by detailed cytoarchitectural histology in the brains of two vocal learning bat species; Phyllostomus discolor and Rousettus aegyptiacus. We show widespread expression of these genes, similar to what has been previously observed in other species, including humans. A striking difference was observed in the adult P. discolor bat, which showed low levels of FoxP2 expression in the cortex that contrasted with patterns found in rodents and nonhuman primates. We created an online, open‐access database within which all data can be browsed, searched, and high resolution images viewed to single cell resolution. The data presented herein reveal regions of interest in the bat brain and provide new opportunities to address the role of these language‐related genes in complex vocal‐motor and vocal learning behaviors in a mammalian model system.
StyLit

We present an approach to example-based stylization of 3D renderings that better preserves the rich expressiveness of hand-created artwork. Unlike previous techniques, which are mainly guided by colors and normals, our approach is based on light propagation in the scene. This novel type of guidance can distinguish among context-dependent illumination effects, for which artists typically use different stylization techniques, and delivers a look closer to realistic artwork. In addition, we demonstrate that the current state of the art in guided texture synthesis produces artifacts that can significantly decrease the fidelity of the synthesized imagery, and propose an improved algorithm that alleviates them. Finally, we demonstrate our method's effectiveness on a variety of scenes and styles, in applications like interactive shading study or autocompletion.
Polycarbonate and polystyrene nanoplastic particles act as stressors to the innate immune system of fathead minnow (Pimephales promelas)

Water pollution with large‐scale and small‐scale plastic litter is an area of growing concern. Macro‐plastic litter is a well‐known threat to aquatic wildlife; however, the effects of micro‐sized and nano‐sized plastic particles on the health of organisms are not well understood. Small‐scale plastic particles can easily be ingested by various aquatic organisms and potentially interfere with their immune system; therefore, the authors used a freshwater fish species as a model organism for nanoplastic exposure. Characterization of polystyrene (41.0 nm) and polycarbonate (158.7 nm) nanoplastic particles (PSNPs and PCNPs, respectively) in plasma was performed, and the effects of PSNPs and PCNPs on the innate immune system of fathead minnow were investigated. In vitro effects of PSNPs and PCNPs on neutrophil function were determined using a battery of neutrophil function assays. Exposure of neutrophils to PSNPs or PCNPs caused significant increases in degranulation of primary granules and neutrophil extracellular trap release compared to a nontreated control, whereas oxidative burst was less affected. The present study outlines the stress response of the cellular component of fish innate immune system to polystyrene and polycarbonate nanoparticles/aggregates and indicates their potential to interfere with disease resistance in fish populations. Environ Toxicol Chem 2016;35:3093–3100. © 2016 SETAC
Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors

Improvement in sinonasal quality of life (QoL) following sinus surgery has been well‐documented across the literature. To our knowledge, only one series has evaluated long‐term QoL in patients undergoing tumor resection, and that study demonstrated no improvement in rhinologic QoL following malignant tumor resection at 2‐year follow‐up. The objective of the present study was to evaluate QoL in the 2 years following endoscopic malignant tumor resection.
Assessment of the Fitbit Charge 2 for monitoring heart rate

Fitness trackers are devices or applications for monitoring and tracking fitness-related metrics such as distance walked or run, calorie consumption, quality of sleep and heart rate. Since accurate heart rate monitoring is essential in fitness training, the objective of this study was to assess the accuracy and precision of the Fitbit Charge 2 for measuring heart rate with respect to a gold standard electrocardiograph. Fifteen healthy participants were asked to ride a stationary bike for 10 minutes and their heart rate was simultaneously recorded from each device. Results showed that the Fitbit Charge 2 underestimates the heart rate. Although the mean bias in measuring heart rate was a modest -5.9 bpm (95% CI: -6.1 to -5.6 bpm), the limits of agreement, which indicate the precision of individual measurements, between the Fitbit Charge 2 and criterion measure were wide (+16.8 to -28.5 bpm) indicating that an individual heart rate measure could plausibly be underestimated by almost 30 bpm.