Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory

Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on which mAChR subtypes are critical for memory processing. Using pharmacological and genetic approaches, we found that (1) encoding and retrieval of contextual memory requires mAChR in the dorsal hippocampus (DH) and retrosplenial cortex (RSC), (2) memory formation requires hippocampal M3 and cooperative activity of RSC M1 and M3, and (3) memory retrieval is more impaired by inactivation of multiple M1–M4 mAChR in DH or RSC than inactivation of individual receptor subtypes. Contrary to the view that acetylcholine supports learning but is detrimental to memory retrieval, we found that coactivation of multiple mAChR is required for retrieval of both recently and remotely acquired context memories. Manipulations with higher receptor specificity were generally less potent than manipulations targeting multiple receptor subtypes, suggesting that mAChR act in synergy to regulate memory processes. These findings provide unique insight into the development of therapies for amnestic symptoms, suggesting that broadly acting, rather than receptor-specific, mAchR agonists and positive allosteric modulators may be the most effective therapeutic approach.
Three‐dimensional models of the segmented human fetal brain generated by magnetic resonance imaging

Recent advances in imaging technology have enabled us to obtain more detailed images of the human fetus in a nondestructive and noninvasive manner. Through detailed images, elaborate three‐dimensional (3D) models of the developing brain can be reconstructed. The segmentation of the developing brain has been determined by serial sections. Therefore, in this study, we attempted to develop a 3D model of the fetal brain using magnetic resonance image (MRI). MR images from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to 225 mm in crown rump length) were used to reconstruct 3D models of regionalized developing brains. From this analysis, we succeeded in registering a maximum of nine landmarks on MR images and reconstructing 19 sequential models of the regionalized developing brain. To confirm the validity of the landmarks, we also compared our results with three serial sections from the Kyoto Collection; the same morphological characteristics were observed on both serial sections and MRI. The morphological minutiae could be found on MR images, and regionalized models of the developing brain could be reconstructed. These results will be useful for clinical diagnosis of living fetuses in utero.
Inventory Decisions and Signals of Demand Uncertainty to Investors

This paper examines how managerial short-termism can affect a firm's inventory decision when external investors have only partial information about the firm's demand uncertainty. We first study the scenario where the manager's short-termism is exogenously given. We derive the full equilibrium spectrum ranging from stable separating to pooling equilibria, which yields insights for learning firms' demand uncertainty from their inventory and sales information and for understanding the effect of managerial short-termism on firm performance. We then analyze the scenario where the manager's short-termism is endogenous. We find that, unlike the scenario with exogenous short-termism, the first-best inventory decisions might be achieved in equilibrium on the basis of an alternative signal.
Leisure time physical activity in relation to depressive symptoms in the black women’s health study

Background: A growing body of evidence suggests that physical activity might reduce the risk of depressive symptoms, but there are limited data on Black women.Purpose: The objective was to evaluate the association between leisure time physical activity and depressive symptoms in U.S. Black women.Methods: Participants included 35,224 women ages 21 to 69 from the BlackWomen’s Health Study, a follow-up study of African American women in which data are collected biennially by mail questionnaire.Women answered questions on past and current exercise levels at baseline (1995) and follow-up (1997). The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms in 1999. Women who reported a diagnosis of depression before 1999 were excluded. We used multivariate logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) for physical activity in relation to depressive symptoms (CES-D score <= 16) with control for potential confounders.Results: Adult vigorous physical activity was inversely associated with depressive symptoms. Women who reported vigorous exercise both in high school (<= 5 hr per week) and adulthood (<= 2 hr per week) had the lowest odds of depressive symptoms (OR = 0.76, 95% CI = 0.71−0.82) relative to never active women; the OR was 0.90 for women who were active in high school but not adulthood (95% CI = 0.85-0.96) and 0.83 for women who were inactive in high school but became active in adulthood (95% CI = 0.77-0.91). Although walking for exercise was not associated with risk of depressive symptoms overall, there was evidence of a weak inverse relation among obese women (Body Mass Index <= 30). Conclusions: Leisure time vigorous physical activity was associated with a reduced odds of depressive symptoms in U.S. Black women.
Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells

ABSTRACT Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancers acquire resistance to EGFR tyrosine kinase inhibitors through multiple mechanisms including c-Met receptor pathway activation. We generated a bispecific antibody targeting EGFR and c-Met (JNJ-61186372) demonstrating anti-tumor activity in wild-type and mutant EGFR settings with c-Met pathway activation. JNJ-61186372 was engineered with low fucosylation (<10 %), resulting in enhanced antibody-dependent cell-mediated cytotoxicity and FcγRIIIa binding. In vitro and in vivo studies with the single-arm EGFR or c-Met versions of JNJ-61186372 identified that the Fc-activity of JNJ-61186372 is mediated by binding of the anti-EGFR arm and required for inhibition of EGFR-driven tumor cells. In a tumor model driven by both EGFR and c-Met, treatment with Fc-silent JNJ-61186372 or with c-Met single-arm antibody reduced tumor growth inhibition compared to treatment with JNJ-61186372, suggesting that the Fc function of JNJ-61186372 is essential for maximal tumor inhibition. Moreover in this same model, downregulation of both EGFR and c-Met receptors was observed upon treatment with Fc-competent JNJ-61186372, suggesting that the Fc interactions are necessary for down-modulation of the receptors in vivo and for efficacy. These Fc-mediated activities, in combination with inhibition of both the EGFR and c-Met signaling pathways, highlight the multiple mechanisms by which JNJ-61186372 combats therapeutic resistance in EGFR mutant patients.
Synthesis of Superhydrophobic Nanocomposite Coatings Using Electrodeposition

The focus of the current research is to produce a metal matrix composite material that possesses a superhydrophobic surface using electrodeposition. The objective is to create a multifunctional coating that is able to provide high strength as well as high water repellency using nanocrystalline nickel and polytetrafluoroethylene (PTFE) particles. The co-deposition process was first studied. It was determined that the amount of PTFE co-deposited is highly dependent on the concentration of PTFE particles in the electroplating bath. The wetting angle of the surface greatly increased when the PTFE content increases. Next the electroplating procedure of pure nickel is altered to produce a nanocrystalline material, resulting in a large increase in the hardness of the nickel coatings. The two techniques are combined to produce a nanocrystalline Nickel-PTFE composite. Under optimum conditions, the composite coating displayed a highly water repellent surface and improved mechanical properties.
Emotional responses to behavioral economic incentives for health behavior change

Abstract Many people aim to change their lifestyle, but have trouble acting on their intentions. Behavioral economic incentives and related emotions can support commitment to personal health goals, but the related emotions remain unexplored. In a regret lottery, winners who do not attain their health goals do not get their prize but receive feedback on what their forgone earnings would have been. This counterfactual feedback should provoke anticipated regret and increase commitment to health goals. We explored which emotions were actually expected upon missing out on a prize due to unsuccessful weight loss and which incentive-characteristics influence their likelihood and intensity. Participants reported their expected emotional response after missing out on a prize in one of 12 randomly presented incentive-scenarios, which varied in incentive type, incentive size and deadline distance. Participants primarily reported feeling disappointment, followed by regret. Regret was expected most when losing a lottery prize (vs. a fixed incentive) and intensified with prize size. Multiple features of the participant and the lottery incentive increase the occurrence and intensity of regret. As such, our findings can be helpful in designing behavioral economic incentives that leverage emotions to support health behavior change.
Dental Fluorosis: Variability among Different Inbred Mouse Strains

Concurrent with the decline in dental caries has been an increase in the prevalence of dental fluorosis, a side-effect of exposure to greater than optimal levels of fluoride during amelogenesis. The mechanisms that underlie the pathogenesis of dental fluorosis are not known. We hypothesize that genetic determinants influence an individual’s susceptibility or resistance to develop dental fluorosis. We tested this hypothesis using a mouse model system (continuous eruption of the incisors) where genotype, age, gender, food, housing, and drinking water fluoride level can be rigorously controlled. Examination of 12 inbred strains of mice showed differences in dental fluorosis susceptibility/resistance. The A/J mouse strain is highly susceptible, with a rapid onset and severe development of dental fluorosis compared with that in the other strains tested, whereas the 129P3/J mouse strain is least affected, with minimal dental fluorosis. These observations support the contribution of a genetic component in the pathogenesis of dental fluorosis.
Destructive Pulmonary Effects of Smoke Inhalation and Simultaneous Alterations in Circulating IL-6, TNF-&agr;, and IFN-&ggr; Levels at Different Burn Depths: An Experimental Study on Rats

The current study sought to examine the interactions between inflammatory and immune events in the lung and circulating interleukin-6 (IL-6), tumor necrosis factor-&agr; (TNF-&agr;), and interferon-&ggr; (IFN-&ggr;) levels at different burn depths with concomitant smoke inhalation in the rat model. Forty-eight female Sprague-Dawley rats were divided into six groups: S, sham; P, partial-thickness burns; F, full-thickness burns; I, inhalation; Pi, partial-thickness burns + inhalation; and Fi, full-thickness burns + inhalation. Blood samples and lung biopsies were obtained 24 hours later. Blood levels of IL-6, TNF-&agr;, and IF-&ggr; were measured with enzyme-linked immunosorbent assay. The proportions of CD3(+) lymphocytes and CD68(+) macrophages in the biopsies were studied immunohistochemically. The most severe inflammatory changes, except the neutrophil sequestration, were observed in the Fi group. A dense amount of neutrophils was observed in the F group. Edema and massive alveolar bleeding were seen in the I, Pi, and Fi groups. The amount of CD3(+) lymphocytes were dense in the P, F, and Pi groups. The amount of CD68(+) macrophages were significantly dense in Pi, F, I, and Fi groups. IL-6, TNF-&agr;, and IF-&ggr; increased in all groups when compared to the S group. The highest IL-6 level was seen in the Fi group. TNF-&agr; significantly increased in the F, Pi, I, and Fi groups. Increase in IFN-&ggr; levels in the Pi and Fi groups was significantly higher than in the P and F groups. In concomitant smoke inhalation and skin burns, pulmonary damage and systemic inflammatory response are related and may be evaluated by blood levels of IL-6, TNF-&agr;, and IFN-&ggr; cytokines.
Overview of the NTCIR-8 ACLIA Tasks: Advanced Cross-Lingual Information Access

paper presents an overview of the ACLIA (Advanced Cross-Lingual Information Access) task cluster at NTCIR-8. The task overview includes: a definition of and motivation for the evaluation; a description of the complex and factoid question types evaluated; the document sources and exchange formats selected and/or defined; the official metrics used in evaluating participant runs; the tools and process used to develop the official evaluation topics; summary data regarding the runs submitted; and the results of evaluating the submitted runs with the official metrics.
Metabolic profiling and novel plasma biomarkers for predicting survival in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies around the world, and patients with ovarian cancer always have an extremely poor chance of survival. Therefore, it is meaningful to develop a highly efficient model that can predict the overall survival for EOC. In order to investigate whether metabolites could be used to predict the survival of EOC, we performed a metabolic analysis of 98 plasma samples with follow-up information, based on the ultra-performance liquid chromatography mass spectrometry (UPLC/MS) systems in both positive (ESI+) and negative (ESI-) modes. Four metabolites: Kynurenine, Acetylcarnitine, PC (42:11), and LPE(22:0/0:0) were selected as potential predictive biomarkers. The AUC value of metabolite-based risk score, together with pathological stages in predicting three-year survival rate was 0.80. The discrimination performance of these four biomarkers between short-term mortality and long-term survival was excellent, with an AUC value of 0.82. In conclusion, our plasma metabolomics study presented the dysregulated metabolism related to the survival of EOC, and plasma metabolites could be utilized to predict the overall survival and discriminate the short-term mortality and long-term survival for EOC patients. These results could provide supplementary information for further study about EOC survival mechanism and guiding the appropriate clinical treatment.
Sociodemographic, developmental, environmental, and psychological correlates of physical activity and sedentary behavior at age 11 to 12

Background: Low levels of physical activity and high levels of sedentary behavior during adolescence are a cause for concern. Sociodemographic, developmental, environmental, and psychological factors may be relevant, but the correlates of these behaviors may differ.Purpose: To investigate the multidimensional correlates of physical activity and sedentary behavior in a large sample of 11- to 12-year-old boys and girls.Methods: Cross-sectional survey of 2,578 boys and 1,742 girls from36 schools stratified by socioeconomic background and gender mix of students (84% response rate). Questionnaire assessments and objective measurements of height and weight were obtained.Results:Days of vigorous physical activity and hours of sedentary behaviors over the past week were uncorrelated. Ethnicity, socioeconomic factors, developmental stage, environmental factors, and psychological variables were associated with physical activity and sedentary behavior in univariate analyses. In multiple regression, sedentary behavior was greater in ethnic minority groups, in students frommore deprived backgrounds,andin those with conduct problems. Girls who were more advanced developmentally and who reported emotional symptoms also engaged in more sedentary behaviors. Vigorous physical activity was associated with good self-rated health, prosocial psychological characteristics, and (in boys) with low emotional symptoms.Conclusions:A multidimensional approach to understanding the context of physical activity in early adolescence is needed because factors in several domains are relevant. The correlates of physical activity and sedentary behaviors are distinct in this age group, and there are also important gender differences.
Calixarenes as High Temperature Matrices for Thermally Activated Delayed Fluorescence: C70 in Dihomooxacalix[4]arene

Thermally activated delayed fluorescence (TADF) of 12C70 and 13C70 was observed up to 140 °C in a p-tert-butyldihomooxacalix[4]arene solid matrix, a temperature range significantly higher than that of previous TADF quantitative studies. An effective singlet–triplet energy gap of 29 kJ/mol and triplet formation quantum yields of 0.97 and 0.99 were measured for 12C70 and 13C70, respectively. The photophysical properties of the two fullerenes in this new matrix are comparable to those obtained in polystyrene at a lower temperature range. Calixarenes are proposed to be suitable matrices for high temperature TADF studies and applications.
TANKYRASE Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR Inhibition, Mutually Affecting β-CATENIN and AKT Signaling in Colorectal Cancer

Overactivation of the WNT/β-CATENIN signaling axis is a common denominator in colorectal cancer. Currently, there is no available WNT inhibitor in clinical practice. Although TANKYRASE (TNKS) inhibitors have been proposed as promising candidates, there are many colorectal cancer models that do not respond positively to TNKS inhibition in vitro and in vivo. Therefore, a combinatorial therapeutic approach combining a TNKS inhibitor (G007-LK) with PI3K (BKM120) and EGFR (erlotinib) inhibitors in colorectal cancer was investigated. The data demonstrate that TNKS inhibition enhances the effect of PI3K and EGFR inhibition in the TNKS inhibitor–sensitive COLO320DM, and in the nonsensitive HCT-15 cell line. In both cell lines, combined TNKS/PI3K/EGFR inhibition is more effective at reducing growth than a dual TNKS/MEK inhibition. TNKS/PI3K/EGFR inhibition affected in a context-dependent manner components of the WNT/β-CATENIN, AKT/mTOR, EGFR, and RAS signaling pathways. TNKS/PI3K/EGFR inhibition also efficiently reduced growth of both COLO320DM and HCT-15 tumor xenografts in vivo. At the highest doses, tumor xenograft growth was halted without affecting the body weight of the tested animals. Implications: Combining TNKS inhibitors with PI3K and EGFR inhibition may expand the therapeutic arsenal against colorectal cancers. Mol Cancer Res; 16(3); 543–53. ©2017 AACR.
The imperiled fish fauna in the Nicaragua Canal zone

Large‐scale infrastructure projects commonly have large effects on the environment. The planned construction of the Nicaragua Canal will irreversibly alter the aquatic environment of Nicaragua in many ways. Two distinct drainage basins (San Juan and Punta Gorda) will be connected and numerous ecosystems will be altered. Considering the project's far‐reaching environmental effects, too few studies on biodiversity have been performed to date. This limits provision of robust environmental impact assessments. We explored the geographic distribution of taxonomic and genetic diversity of freshwater fish species (Poecilia spp., Amatitlania siquia, Hypsophrys nematopus, Brycon guatemalensis, and Roeboides bouchellei) across the Nicaragua Canal zone. We collected population samples in affected areas (San Juan, Punta Gorda, and Escondido drainage basins), investigated species composition of 2 drainage basins and performed genetic analyses (genetic diversity, analysis of molecular variance) based on mitochondrial cytb. Freshwater fish faunas differed substantially between drainage basins (Jaccard similarity = 0.33). Most populations from distinct drainage basins were genetically differentiated. Removing the geographic barrier between these basins will promote biotic homogenization and the loss of unique genetic diversity. We found species in areas where they were not known to exist, including an undescribed, highly distinct clade of live bearing fish (Poecilia). Our results indicate that the Nicaragua Canal likely will have strong impacts on Nicaragua's freshwater biodiversity. However, knowledge about the extent of these impacts is lacking, which highlights the need for more thorough investigations before the environment is altered irreversibly.
The Impact of Maltitol-Sweetened Chewing Gum on the Dental Plaque Biofilm Microbiota Composition

Background: The oral cavity harbors a complex microbial ecosystem, intimately related to oral health and disease. The use of polyol-sweetened gum is believed to benefit oral health through stimulation of salivary flow and impacting oral pathogenic bacteria. Maltitol is often used as sweetener in food products. This study aimed to establish the in vivo effects of frequent consumption of maltitol-sweetened chewing gum on the dental plaque microbiota in healthy volunteers and to establish the cellular and molecular effects by in vitro cultivation and transcriptional analysis. Results: An intervention study was performed in 153 volunteers, randomly assigned to three groups (www.trialregister.nl; NTR4165). One group was requested to use maltitol gum five times daily, one group used gum-base, and the third group did not use chewing gum. At day 0 and day 28, 24 h-accumulated supragingival plaque was collected at the lingual sites of the lower jaw and the buccal sites of the upper jaw and analyzed by 16S ribosomal rRNA gene sequencing. At day 42, 2 weeks after completion of the study, lower-jaw samples were collected and analyzed. The upper buccal plaque microbiota composition had lower bacterial levels and higher relative abundances of (facultative) aerobic species compared to the lower lingual sites. There was no difference in bacterial community structure between any of the three study groups (PERMANOVA). Significant lower abundance of several bacterial phylotypes was found in maltitol gum group compared to the gum-base group, including Actinomyces massiliensis HOT 852 and Lautropia mirabilis HOT 022. Cultivation studies confirmed growth inhibition of A. massiliensis and A. johnsonii by maltitol at levels of 1% and higher. Transcriptome analysis of A. massiliensis revealed that exposure to maltitol resulted in changes in the expression of genes linked to osmoregulation, biofilm formation, and central carbon metabolism. Conclusion: The results showed that chewing itself only marginally impacted the plaque microbiota composition. Use of maltitol-sweetened gum lowered abundance of several bacterial species. Importantly, the species impacted play a key role in the early formation of dental biofilms. Further studies are required to establish if frequent use of maltitol gum impacts early dental-plaque biofilm development.