Miracle-dz/UniFAR-FTUs huggingface dataset:
A High-Content, Multiplexed Screen in Human Breast Cancer Cells Identifies Profilin-1 Inducers with Anti-Migratory Activities

Profilin-1 (Pfn-1) is a ubiquitously expressed actin-binding protein that is essential for normal cell proliferation and migration. In breast cancer and several other adenocarcinomas, Pfn-1 expression is downregulated when compared to normal tissues. Previous studies from our laboratory have shown that genetically modulating Pfn-1 expression significantly impacts proliferation, migration, and invasion of breast cancer cells in vitro, and mammary tumor growth, dissemination, and metastatic colonization in vivo. Therefore, small molecules that can modulate Pfn-1 expression could have therapeutic potential in the treatment of metastatic breast cancer. The overall goal of this study was to perform a multiplexed phenotypic screen to identify compounds that inhibit cell motility through upregulation of Pfn-1. Screening of a test cassette of 1280 compounds with known biological activities on an Oris™ Pro 384 cell migration platform identified several agents that increased Pfn-1 expression greater than two-fold over vehicle controls and exerted anti-migratory effects in the absence of overt cytotoxicity in MDA-MB-231 human breast cancer cells. Concentration-response confirmation and orthogonal follow-up assays identified two bona fide inducers of Pfn-1, purvalanol and tyrphostin A9, that confirmed in single-cell motility assays and Western blot analyses. SiRNA-mediated knockdown of Pfn-1 abrogated the inhibitory effect of tyrphostin A9 on cell migration, suggesting Pfn-1 is mechanistically linked to tyrphostin A9′s anti-migratory activity. The data illustrate the utility of the high-content cell motility assay to discover novel targeted anti-migratory agents by integrating functional phenotypic analyses with target-specific readouts in a single assay platform.
Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents

More rapid skeletal maturation in African‐American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non‐obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed‐longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand‐wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual‐energy X‐ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self‐reported AA girls (∼0.33 years, p < 0.001) and boys (∼0.43 years, p < 0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self‐report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self‐report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non‐obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research.
The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability

Abstract Aims Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 variant on cardiac ion channel function and membrane excitability. Methods and results We transfected either the wild type (WT) or T78M cav-3 in caveolin-1 knock-out mouse embryonic fibroblasts and found by immunofluorescence and electron microscopy that both are expressed at the plasma membrane and form caveolae. Two ion channels known to interact and co-immunoprecipitate with the cav-3, hKv1.5 and hHCN4, interact also with T78M cav-3 and reside in lipid rafts. Electrophysiological analysis showed that the T78M cav-3 causes hKv1.5 channels to activate and inactivate at more hyperpolarized potentials and the hHCN4 channels to activate at more depolarized potentials, in a dominant way. In spontaneously beating neonatal cardiomyocytes, the expression of the T78M cav-3 significantly increased action potential peak-to-peak variability without altering neither the mean rate nor the maximum diastolic potential. We also found that in a small cohort of patients with supraventricular arrhythmias, the T78M cav-3 variant is more frequent than in the general population. Finally, in silico analysis of both sinoatrial and atrial cell models confirmed that the T78M-dependent changes are compatible with a pro-arrhythmic effect. Conclusion This study demonstrates that the T78M cav-3 induces complex modifications in ion channel function that ultimately alter membrane excitability. The presence of the T78M cav-3 can thus generate a susceptible substrate that, in concert with other structural alterations and/or genetic mutations, may become arrhythmogenic.
Interfacial Bond Strength Characteristics of FRP and RC Substrate

AbstractThis study focuses on the development of a fracture-mechanics-based model that predicts the debonding behavior of RC beams strengthened with fiber-reinforced polymer (FRP). In this study, the existing debonding models based on fracture mechanics are reviewed. Since no approach exists that can exactly predict the failure mode, an extensive database that contains different beam debonding failure modes was prepared. This database includes 351 concrete prisms bonded with FRP plates tested in single and double shear. The existing fracture-mechanics-based models were applied to this database. The new proposed model was based on newly conducted carbon-fiber-reinforced polymer (CFRP)-to-concrete single shear tests and data were collected from two independent studies. A comparison between the experimental and the analytical results showed that the model predicts the bond strength accurately.
Cumulative object categorization in clutter

In this paper we present an approach based on scene- or part-graphs for geometrically categorizing touching and occluded objects, using additive RGBD feature descriptors and hashing of graph configuration parameters for describing the spatial arrangement of constituent parts. The presented experiments quantify that this method outperforms our earlier part-voting and sliding window classification. We evaluated our approach on cluttered scenes, and by using a 3D dataset containing over 15000 Kinect scans of over 100 objects which were grouped into general geometric categories. Additionally, color, geometric, and combined features were compared for categorization tasks.
Combination therapy for inhibitor reversal in haemophilia A using monoclonal anti-CD20 and rapamycin

Summary Development of antibodies (inhibitors) against coagulation factor VIII (FVIII) is a major complication of intravenous replacement therapy in haemophilia A (HA). Current immune tolerance induction (ITI) regimens are not universally effective. Rituximab, a B cell-depleting antibody against CD20, has shown mixed results for inhibitor reversal in patients. This study aims to develop a combinatorial therapy for inhibitor reversal in HA, using anti-murine CD20 (anti-mCD20) antibody and rapamycin, which targets both B and T cell responses. Additionally, it extensively characterises the role of the IgG backbone in B cell depletion by anti-CD20 antibodies. For this, inhibitors were generated in BALB/c-HA mice by weekly IV injection of FVIII. Subsequently, anti-mCD20 (18B12) with IgG2a or IgG1 backbone was injected IV in two doses three weeks apart and B cell depletion and recovery was characterised. Rapamycin was administered orally 3x/week (for 1 month) while continuing FVIII injections. Altering the IgG backbone of anti-mCD20 from IgG2a to IgG1 reduced overall depletion of B cells (including memory B cells), and marginal zone, B-10, and B-1b cells were specifically unaffected. While neither antibody was effective alone, in combination with rapamycin, anti-mCD20 IgG2a but not IgG1 was able to reverse inhibitors in HA mice. This regimen was particularly effective for starting titres of ∼10 BU. Although IgG1 anti-mCD20 spared potentially tolerogenic B cell subsets, IgG2a directed sustained hyporesponsiveness when administered in conjunction with rapamycin. This regimen represents a promising treatment for inhibitor reversal in HA, as both of these compounds have been extensively used in human patients. Supplementary Material to this article is available at www.thrombosis-online.com.
Comparative Analysis of the Mitochondrial Genomes of Callitettixini Spittlebugs (Hemiptera: Cercopidae) Confirms the Overall High Evolutionary Speed of the AT-Rich Region but Reveals the Presence of Short Conservative Elements at the Tribal Level

The present study compares the mitochondrial genomes of five species of the spittlebug tribe Callitettixini (Hemiptera: Cercopoidea: Cercopidae) from eastern Asia. All genomes of the five species sequenced are circular double-stranded DNA molecules and range from 15,222 to 15,637 bp in length. They contain 22 tRNA genes, 13 protein coding genes (PCGs) and 2 rRNA genes and share the putative ancestral gene arrangement of insects. The PCGs show an extreme bias of nucleotide and amino acid composition. Significant differences of the substitution rates among the different genes as well as the different codon position of each PCG are revealed by the comparative evolutionary analyses. The substitution speeds of the first and second codon position of different PCGs are negatively correlated with their GC content. Among the five species, the AT-rich region features great differences in length and pattern and generally shows a 2–5 times higher substitution rate than the fastest PCG in the mitochondrial genome, atp8. Despite the significant variability in length, short conservative segments were identified in the AT-rich region within Callitettixini, although absent from the other groups of the spittlebug superfamily Cercopoidea.
Pregnant Women Sharing Pregnancy-Related Information on Facebook: Web-Based Survey Study

Background Research indicates expectant and new mothers use the Internet, specifically social media, to gain information and support during the transition to parenthood. Although parents regularly share information about and photos of their child or children on Facebook, researchers have neither explored the use of Facebook to share pregnancy-related information nor investigated factors that influence such sharing. Objective The aim of this study was to address a gap in the literature by exploring the use of Facebook by pregnant women. Specifically, the study examined the use of Facebook to share pregnancy-related information, as well as any association between prenatal attachment and the aforementioned aspects of sharing pregnancy-related information on Facebook. Methods Pregnant women who were at least 18 years of age were recruited for participation in the study through posts and paid advertisements on Facebook and posts to professional organization listservs. Individuals interested in participating were directed to a secure Web-based survey system where they completed the consent form and the survey that focused on their current pregnancy. Participants completed the Maternal Antenatal Attachment Scale and answered questions that assessed how often they shared pregnancy-related information on Facebook, who they shared it with, why they shared it, and what they shared. Results A total of 117 pregnant women completed the survey. Descriptive statistics indicated that the pregnancy announcement was most commonly shared (75/108, 69.4%), with most women sharing pregnancy-related information on Facebook less than monthly (52/117, 44.4%) with only family and friends (90/116, 77.6% and 91/116, 78.4%, respectively) and for the purpose of involving others or sharing the experience (62/107, 57.9%). Correlation and regression analyses showed that prenatal attachment, in general, was positively and significantly related to all aspects of sharing pregnancy-related information at the P<. 05 level, with the exception of sharing because of expectations. Quality of attachment, which involves the positive feelings the woman has about her unborn child, was significantly associated with sharing to involve others or share the pregnancy (t8,93=2.654 , P=.009). In contrast, after controlling for other variables, the strength or preoccupation component of prenatal attachment was significantly associated with frequency of sharing (t8,100=2.554 , P=.01), number to types of information shared (t8,97=2.605 , P=.01), number of groups with whom shared (t8,99=3.467, P=.001), and sharing to get advice (χ28=5.339 , P=.02). Conclusions Pregnant women in this study used Facebook for a variety of reasons, demonstrating the use of the social media platform during pregnancy for supportive and informational purposes. Overall, the results of this study are likely to be useful to professionals who are seeking alternative methods for providing intervention, information, and support to pregnant women via social media in our technology-driven society.
Addressing resin loss and gloving issues at a mine with coal roof

Over the last year, Jennmar has been supplying roof bolts to a new mine with a thick coal roof in which massive resin loss was being measured. After trying various drill hole diameters, bolt profiles and available viscosities of resin, the mine still did not achieve their designed 90% encapsulation which meant an extra two bolts per metre were being installed. Over-coring to determine where the resin was going revealed that near vertical coal cleat was filling with resin but it also revealed that bolts were gloved for over 50% of their length. Extensive in situ testing achieved some interesting new data applicable to that mine site: 1) short encapsulation pull testing of gloved sections of bolt gave similar bond strength to the non-gloved bolts; 2) high viscosity (thick) resin gave improved encapsulation and 3) gloving could only be significantly reduced by a modified bolt end that nearly contacted the side of the bolt hole. Testing methods and results achieved along with comparing them to methods and results from previous literature on roof bolt gloving investigations are reported.
Grasping virtual fish: A step towards robotic deep learning from demonstration in virtual reality

We present an approach to robotic deep learning from demonstration in virtual reality, which combines a deep 3D convolutional neural network, for grasp detection from 3D point clouds, with domain randomization to generate a large training data set. The use of virtual reality (VR) enables robot learning from demonstration in a virtual environment. In this environment, a human user can easily and intuitively demonstrate examples of how to grasp an object, such as a fish. From a few dozen of these demonstrations, we use domain randomization to generate a large synthetic training data set consisting of 76 000 example grasps of fish. After training the network using this data set, the network is able to guide a gripper to grasp virtual fish with good success rates. Our domain randomization approach is a step towards an efficient way to perform robotic deep learning from demonstration in virtual reality.
WHO Class of Obesity Influences Functional Recovery Post-TKA

Background No study in the literature has compared early functional recovery following total knee arthroplasty (TKA) in the obese with the nonobese using World Health Organization (WHO) classes of obesity. Our aim was to compare functional scores and flexion post-TKA in each class of obesity as per WHO classification against a matched control group of nonobese patients. Methods Records of 885 consecutive primary TKA patients (919 knees) operated by a single surgeon were reviewed. The first 35 knees in each class I, class II and class III obesity group during the study period were then matched with a similar number of knees in nonobese TKA patients during the same period. Functional scores recorded pre- and postoperatively at 3 months and 1 year were Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short-Form Health Survey (SF-12) score, and Knee Society Score (KSS). Results There was no difference in any parameter between the class I obese and matched nonobese at any assessment point. In the class II obese, as compared to the nonobese, there was no difference in any parameter preoperatively and 3 months postoperatively. However, 1 year postoperatively, the SF-12 physical subscore was lower in the class II obese than the nonobese (44.7 vs. 48.6, p = 0.047) and the WOMAC score was significantly higher (15.8 vs. 9.7, p = 0.04). In the class III obese, the WOMAC score was significantly higher than the nonobese (58.1 vs. 44.3, p < 0.001 preoperatively; 15.7 vs. 8.1, p = 0.005 at 1 year) and KSS was significantly lower (83.5 vs. 96.5, p = 0.049 preoperatively; 172 vs. 185; p = 0.003 at 1 year). Knee flexion was significantly lower in the class III obese than the nonobese (95 vs. 113; p < 0.001 preoperatively; 120 vs. 127; p = 0.002 at 1 year). Conclusions The class I obese can expect good early and late functional recovery as the nonobese. The class II obese can expect comparable early functional recovery as the nonobese but their late function may be lesser. The class III obese would have poorer functional scores and lesser knee flexion postoperatively compared to the nonobese. However, compared to their own preoperative status, there is definite improvement in function and knee flexion.
The instability of graded structure: implications for the nature of concepts

After a brief introduction to graded structure, this chapter reviews empirical findings showing that the graded structure of a category is unstable, varying widely across contexts. Implications of these findings for theories of categorization are discussed, and it is concluded that graded structures do not represent invariant structural characteristics of Categories. Instead it is proposed that in stability in graded structure occurs because different concept temporarily represent the same categoy in working memory on different occasions.Rather than being retrieved as static units from memory to represent categories, concepts originate in a highly flexible process that retrieves generic and episodic information from long-term memory to construct temporary concepts in Work-ing memorу. Because this concept construction process is highly constrained by goals, context, and jecent experience, the same concept is rarely if ever constructed for a category. A theory of concept construction is presented, and the relations of this theory to dreaming (Foulkes 1985), conceptual combination (Hampton in press a,b; Smith & Osherson 1984), exemplar theories (Brooks 1978; Jacoby & Brooks .1984; Media & Schaeffer 1978), norm theory (Kaimeman &: Miller, 1986), and parallel distributed processing (McClelland & Rumelhart 1986; Rumelhart & McClelland, 1986) are discussed.
Effects of genotype and environment on the starch properties and end-product quality of oats

ABSTRACT Five Canadian oat genotypes were grown at six environments in Manitoba to assess the effects of genotype, environment, and genotype-by-environment interaction on oat starch properties and end-product quality. Genotypic variation was significant for total starch, amylose content, starch swelling volume (SSV), Rapid Visco Analyser (RVA) pasting viscosities, differential scanning calorimetry (DSC) thermal properties, and starch gel texture as well as the quality of flakes and cooked oatmeal made by laboratory-scale methodologies. Environment was the dominant factor contributing to the total variation of starch content, RVA pasting viscosities, SSV, and DSC thermal properties. Most measurements of starch gel and oatmeal texture were not affected by growing environment. Cross-over analysis revealed that changes in the ranking of genotypes across environments occurred for starch RVA hot paste, breakdown and shear thinning viscosities, work of gel compression, flake hydration capacity, and the proportio.
Career Development under the Lifetime Employment System of Japanese Organizations

The ideal concept of lifetime employment in Japan implies that an individual eareer evolves during a person's working life within only one corporation typicaliy chosen upon graduating from sehool. Under this system, an individual career bears the following features. First, for the individual, choosing a company represents a lifelong commitment He will accept and anticipate career clevelopment opportunities
A Self-rating Scale for Bulimia the ‘BITE’

A new brief questionnaire, the Bulimic Investigatory Test, Edinburgh (BITE), for the detection and description of binge-eating is described. Data from two separate populations demonstrate satisfactory reliability and validity. The scale has measures of both symptoms and severity. All items in the DSM-III definition of bulimia and Russell's definition of bulimia nervosa are covered but the questionnaire is more than just an operationalised checklist of these diagnostic criteria.
Accurate and Rapid Identification of the Burkholderia pseudomallei Near-Neighbour, Burkholderia ubonensis, Using Real-Time PCR

Burkholderia ubonensis is an environmental bacterium belonging to the Burkholderia cepacia complex (Bcc), a group of genetically related organisms that are associated with opportunistic but generally nonfatal infections in healthy individuals. In contrast, the near-neighbour species Burkholderia pseudomallei causes melioidosis, a disease that can be fatal in up to 95% of cases if left untreated. B. ubonensis is frequently misidentified as B. pseudomallei from soil samples using selective culturing on Ashdown’s medium, reflecting both the shared environmental niche and morphological similarities of these species. Additionally, B. ubonensis shows potential as an important biocontrol agent in B. pseudomallei-endemic regions as certain strains possess antagonistic properties towards B. pseudomallei. Current methods for characterising B. ubonensis are laborious, time-consuming and costly, and as such this bacterium remains poorly studied. The aim of our study was to develop a rapid and inexpensive real-time PCR-based assay specific for B. ubonensis. We demonstrate that a novel B. ubonensis-specific assay, Bu550, accurately differentiates B. ubonensis from B. pseudomallei and other species that grow on selective Ashdown’s agar. We anticipate that Bu550 will catalyse research on B. ubonensis by enabling rapid identification of this organism from Ashdown’s-positive colonies that are not B. pseudomallei.