Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ∼5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ‐cell mutagens, no human germ‐cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ‐cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ‐cell mutagenesis. Workshop participants recommended large‐scale human germ‐cell mutation studies be conducted using samples from donors with high‐dose exposures, such as cancer survivors. Within this high‐risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio‐bank of human tissue samples from donors with well‐characterized exposure, including medical and reproductive histories. This mutational resource could support large‐scale, multiple‐endpoint studies. Additional studies could involve the examination of transgenerational effects associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germ‐cell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ‐cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full‐scale assault to address key fundamental questions in human germ‐cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ‐cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ‐cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ‐cell mutagenesis. Environ. Mol. Mutagen. , 2007. Published 2007 Wiley‐Liss, Inc.
The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush

The structure and properties of amyloid-like Tau fibrils accumulating in neurodegenerative diseases have been debated for decades. Although the core of Tau fibrils assembles from short β-strands, the properties of the much longer unstructured Tau domains protruding from the fibril core remain largely obscure. Applying immunogold transmission EM, and force-volume atomic force microscopy (AFM), we imaged human Tau fibrils at high resolution and simultaneously mapped their mechanical and adhesive properties. Tau fibrils showed a ≈16-nm–thick fuzzy coat that resembles a two-layered polyelectrolyte brush, which is formed by the unstructured short C-terminal and long N-terminal Tau domains. The mechanical and adhesive properties of the fuzzy coat are modulated by electrolytes and pH, and thus by the cellular environment. These unique properties of the fuzzy coat help in understanding how Tau fibrils disturb cellular interactions and accumulate in neurofibrillary tangles.
Dissociable Roles for Working Memory in Sensorimotor Learning

The computations underlying cognitive strategies in sensorimotor learning are poorly understood. Here we investigate such strategies in a sensorimotor transformation task. We show that strategies assume two forms, reflecting distinct working memory representations: discrete response caching of stimulus-response contingencies (e.g., look-up table; RC), and time-consuming parametric computations (e.g. mental rotation; MR). Subjects’ reaction times and errors suggest that both strategies are employed during learning, and trade off based on the progress of learning and the complexity of the task. Experiments using pressured preparation time support these working memory mechanisms: In discrete RC, time pressure elicits bimodal distributions of movements, in agreement with cached responses; in parametric MR, time pressure elicits a shifting distribution producing intermediate movements between visual targets and distal goals, consistent with analog re-computing of a movement plan. These results provide a specific model of working memory contributions to motor learning.
Longitudinal changes in cortical thinning associated with hypertension

Background: Cross-sectional studies of the association between hypertension (HTN) and brain atrophy have shown reductions in prefrontal, temporal, and hippocampal volumes, and have identified thinner cortices across the cortical mantle. Method: In the current study, we followed 96 participants enrolled in the Baltimore Longitudinal Study of Aging over a mean interval of 8 years (mean age at baseline = 68.7) and compared those who are hypertensive (n = 49) throughout the study with those who are normotensive (n = 47). Results: Hypertensive individuals show an increased rate of thinning compared with normotensive individuals in several regions, including the frontomarginal gyrus in the left hemisphere, and the superior temporal, fusiform, and lateral orbitofrontal cortex in the right hemisphere. We also investigated the effects of midlife blood pressure (BP), intervisit variability in BP prior to imaging, and duration of HTN on areas that show subsequent differences in the rates of cortical thinning between groups. We found that higher midlife BP and longer durations of HTN predicted a higher rate of thinning in the right superior temporal gyrus. We also found that greater variability in SBP but not DBP predicted a higher rate of thinning in the right superior temporal gyrus, frontomarginal gyrus, and occipital pole. Conclusion: These findings demonstrate that hypertensive individuals show increased rates of thinning compared with normotensive individuals and suggest intervisit BP variability and midlife BP contribute to these longitudinal differences.
Named Entity Disambiguation Leveraging Multi-aspect Information

Named Entity Disambiguation (NED) aims at disambiguating named entity mentions in a text to their corresponding entries in a knowledge base such as Wikipedia. Itis a fundamental task in Natural Language Processing (NLP)and has many applications such as information extraction, information retrieval, and knowledge acquisition. In the past decade, a number of methods have been proposed for the NED task. However, most of existing work focuses on exploring many more useful information to help tackle this problem. The effectiveness of different features proposed for the task are not well-studied in a same platform. In this paper, we extract various remarkable features by leveraging statistical, textual and semantic information, and evaluate various combinations of the multiaspect features for the disambiguation task in the same platform. Specifically, we utilize two learning to rank methods to combine different features, train and test the combined methods on several standard data sets. Through extensive experiments, we investigate the effects on the quality of the disambiguation of exploiting different features and show which combinations of features are the best choices for disambiguation.
Analysis and Design of Low-Duty Protocol for Smartphone Neighbor Discovery

An effective neighbor discovery service on smartphones is required for many emerging applications—from proximity-based interactions to opportunistic phone-to-phone collaborations. For a smartphone neighbor discovery service to be usable and attractive, it needs to meet two conflicting goals: 1) phones should discover neighbors fast enough (in seconds), and 2) the service’s energy footprint should be negligible so it can be “always on” while incurring little impact on battery life. Researchers have developed an impressive collection of neighbor discovery protocols to meet these two goals. By putting these protocols into concrete smartphones settings, we identify different key factors that limit their performance. Guided by our analysis, we focus on locally synchronized protocols, where phones use time information from nearby Wi-Fi Access Points (APs) to help neighbor discovery. By overcoming the key challenges for such protocols, especially, the scalability problem under increasing number of APs and neighbors, we design a new protocol, R2, that achieves low discovery delay (<inline-formula> <tex-math notation="LaTeX">$<30$</tex-math><alternatives><inline-graphic xlink:href="guo-ieq1-2693369.gif"/> </alternatives></inline-formula> seconds for at least 80 percent of all connections) with a low duty cycle (1 percent).
5‐HT radioligands for human brain imaging with PET and SPECT

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5‐HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5‐HT) receptors, the 5‐HT transporter (SERT), and 5‐HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5‐HT system in humans include antagonists for the 5‐HT1A, 5‐HT1B, 5‐HT2A, and 5‐HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging. © 2011 Wiley Periodicals, Inc.
Chronic chorioamnionitis displays distinct alterations of the amniotic fluid proteome

Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin‐6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra‐amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age‐matched controls were analysed by two‐dimensional (2D) difference in gel electrophoresis and MALDI–TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin‐6, CXCL8, CXCL10 and prostaglandin F2α were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin‐A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti‐fetal allograft rejection. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Phage Display–Derived Peptides for Osteosarcoma Imaging

Purpose: Osteosarcoma represents the most common malignant primary bone tumor in childhood; however, the survival rate has remained unchanged for the past 20 years. To improve existing diagnosis and treatment methods and broaden the spectrum of imaging agents that can be used for early detection and assessment of tumor response to therapy, we performed a phage display–based screening for peptide sequences that bind specifically to osteosarcoma cells. Experimental Design: From the Ph.D.-12 phage display peptide library composed of 2.7 × 109 different displayed peptides, one peptide was enriched after four rounds of in vitro selection in 143B osteosarcoma tumor cells with 293T human embryonic kidney cells as a control. Both the peptide and the phage clone displaying the peptide were conjugated with fluorescent dyes for in vitro cell and ex vivo tumor tissue stainings. The peptide was further labeled with 18F for positron emission tomography imaging studies. Cell uptake and efflux and ex vivo biodistribution were also done with 18F-labeled osteosarcoma specific peptide. Results: ASGALSPSRLDT was the dominant sequence isolated from biopanning and named as OSP-1. OSP-1 shares a significant homology with heparinase II/III family protein, which binds and reacts with heparan sulfate proteoglycans. The fluorescence staining showed that FITC-OSP-1-phage or Cy5.5-OSP-1 had high binding with a panel of osteosarcoma cell lines, much less binding with UM-SCC1 human head and neck squamous cell carcinoma cells, and almost no binding with 293T cells, whereas the scrambled peptide OSP-S had virtually no binding to all the cell lines. 18F-OSP-1 had significantly higher accumulation in 143B tumor cells both in vitro and in vivo than 18F-OSP-S. 18F-OSP-1 also had higher uptake in 143B tumors than in UM-SCC-1 tumors. Conclusions: Our data suggest that OSP-1 peptide is osteosarcoma specific, and the binding site of OSP-1 might be related to heparan sulfate proteoglycans. Appropriately labeled OSP-1 peptide has the potential to serve as a novel probe for osteosarcoma imaging. Clin Cancer Res; 16(16); 4268–77. ©2010 AACR.
Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF‐β3–Associated Chondrogenesis of Bone Marrow–Derived Mesenchymal Stem Cells for Articular Surface Regeneration

Articular cartilage repair remains a challenging problem. Based on a high‐throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF‐β3) strongly potentiated chondrogenic differentiation of human bone marrow–derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF‐β3–treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF‐β3–induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF‐β3–associated chondrogenesis, and suggest that the FA/TGF‐β3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF‐β3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells. © 2015 American Society for Bone and Mineral Research.
LncKdm2b controls self‐renewal of embryonic stem cells via activating expression of transcription factor Zbtb3

Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that lncKdm2b, a divergent lncRNA for Kdm2b gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. LncKdm2b knockout impairs ESC self‐renewal and causes early embryonic lethality. LncKdm2b can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2‐related CREBBP activator protein (SRCAP) complex in trans. Zbtb3 potentiates the ESC self‐renewal in a Nanog‐dependent manner. Finally, Zbtb3 deficiency impairs the ESC self‐renewal and early embryonic development. Therefore, our findings reveal that lncRNAs may represent an additional layer of the regulation of ESC self‐renewal and early embryogenesis.
Power Lines: Toward a Feminism of Radical Belonging

Like the complex systems of man-made power lines that transmit electricity and connect people and places, feminist alliances are elaborate networks that have the potential to provide access to institutional power and to transform relations. In Power Lines , Aimee Carrillo Rowe explores the formation and transformative possibilities of transracial feminist alliances. She draws on her conversations with twenty-eight self-defined academic feminists, who reflect on their academic careers, alliances, feminist struggles, and identifications. Based on those conversations and her own experiences as an Anglo-Chicana queer feminist researcher, Carrillo Rowe investigates when and under what conditions transracial feminist alliances in academia work or fail, and how close attention to their formation provides the theoretical and political groundwork for a collective vision of subjectivity. Combining theory, criticism, and narrative nonfiction, Carrillo Rowe develops a politics of relation that encourages the formation of feminist alliances across racial and other boundaries within academia. Such a politics of relation is founded on her belief that our subjectivities emerge in community; our affective investments inform and even create our political investments. Thus experience, consciousness, and agency must be understood as coalitional rather than individual endeavors. Carrillo Rowe’s conversations with academic feminists reveal that women who restrict their primary allies to women of their same race tend to have limited notions of feminism, whereas women who build transracial alliances cultivate more nuanced, intersectional, and politically transformative feminisms. For Carrillo Rowe, the institutionalization of feminism is not so much an achievement as an ongoing relational process. In Power Lines , she offers a set of critical, practical, and theoretical tools for building and maintaining transracial feminist alliances.
Riding the Lines and Overwriting in the Margins

This case study examines the multimodal literacy practices of 11-year-old Nigel as he plays with assemblages of people, objects, and practices in his storywriting. The study asks “How does following the seemingly off-task multimodal literacy practices of one pre-adolescent youth across his home-community-school terrain provide insight into contemporary literacy learning and instruction? ” Using assemblage theory, the article maps a period in time, the early months of his fifth-grade experience, when one boy approached the literacies privileged in his classroom with what appeared to be a certain amount of disregard, while engaging in personal literacy practices that were both rich and, at times, subversive. The analysis maps the people, signs, material objects, events, and places in the unfolding of Nigel’s play with two symbolic figures, the line rider and the stick man. Viewed across time and place, Nigel’s textual and embodied play with these figures demonstrate ways a young adolescent, fully immersed in and engaged with his digital and material world, “overwrites” official texts and produces rich stories that go unnoticed by the adults around him. This unfolding took place in unpredictable ways, and as it occurred, literacy practices that brought intellectual and visceral engagement, pleasure and pride, and agentive recourse to Nigel in his practice of literacy came into focus. The emergence of Nigel’s inscriptions across multiple terrains provides insight into ways in which a socio-material perspective, with its focus on the role of affect and the body, may assist us in re-thinking multimodal writing development.
ExAtlas: An interactive online tool for meta-analysis of gene expression data

We have developed ExAtlas, an on-line software tool for meta-analysis and visualization of gene expression data. In contrast to existing software tools, ExAtlas compares multi-component data sets and generates results for all combinations (e.g. all gene expression profiles versus all Gene Ontology annotations). ExAtlas handles both users' own data and data extracted semi-automatically from the public repository (GEO/NCBI database). ExAtlas provides a variety of tools for meta-analyses: (1) standard meta-analysis (fixed effects, random effects, z-score, and Fisher's methods); (2) analyses of global correlations between gene expression data sets; (3) gene set enrichment; (4) gene set overlap; (5) gene association by expression profile; (6) gene specificity; and (7) statistical analysis (ANOVA, pairwise comparison, and PCA). ExAtlas produces graphical outputs, including heatmaps, scatter-plots, bar-charts, and three-dimensional images. Some of the most widely used public data sets (e.g. GNF/BioGPS, Gene Ontology, KEGG, GAD phenotypes, BrainScan, ENCODE ChIP-seq, and protein-protein interaction) are pre-loaded and can be used for functional annotations.