311 research outputs found
Graph-Based Decoding Model for Functional Alignment of Unaligned fMRI Data
Aggregating multi-subject functional magnetic resonance imaging (fMRI) data
is indispensable for generating valid and general inferences from patterns
distributed across human brains. The disparities in anatomical structures and
functional topographies of human brains warrant aligning fMRI data across
subjects. However, the existing functional alignment methods cannot handle well
various kinds of fMRI datasets today, especially when they are not
temporally-aligned, i.e., some of the subjects probably lack the responses to
some stimuli, or different subjects might follow different sequences of
stimuli. In this paper, a cross-subject graph that depicts the
(dis)similarities between samples across subjects is used as a priori for
developing a more flexible framework that suits an assortment of fMRI datasets.
However, the high dimension of fMRI data and the use of multiple subjects makes
the crude framework time-consuming or unpractical. To address this issue, we
further regularize the framework, so that a novel feasible kernel-based
optimization, which permits nonlinear feature extraction, could be
theoretically developed. Specifically, a low-dimension assumption is imposed on
each new feature space to avoid overfitting caused by the
highspatial-low-temporal resolution of fMRI data. Experimental results on five
datasets suggest that the proposed method is not only superior to several
state-of-the-art methods on temporally-aligned fMRI data, but also suitable for
dealing `with temporally-unaligned fMRI data.Comment: 17 pages, 10 figures, Proceedings of the Association for the
Advancement of Artificial Intelligence (AAAI-20
Housing prices and household savings: evidence from urban China
Based on precautionary saving motives, this research develops a three-period life-cycle model to manifest the impact of housing prices on household savings in urban China. The theoretical model illustrates that the expected appreciation of housing prices at a household’s middle age leads to the increase in household savings at a household’s young age. Second, household savings at a household’s young age are positively associated with both expected educational and medical expenditures in a household’s middle age and pension expenditures at a household’s old age. Third, the expected housing prices crowd out educational and medical expenditures at a household’s middle age. With the panel data sets of China’s 31 provinces during 1996–2016, results suggest that the expected housing prices significantly interact with the current household savings. However, the influence of the expected housing prices on the current household savings is greater than that of the current household savings on the expected housing prices. Third, the expected expenditures of education, medical care and pension fuel up the current household savings. Meanwhile, the housing prices crowd out the expenditures of education, medical care and pension. Finally, data of the Urban Household Survey (UHS) over the period 2002–2007 show that the household head age has an effect of reverse U-shape on household savings. Accordingly, to prevent a housing bubble and promote household consumption, policy makers should curb housing price inflation by enacting appropriate countercyclical housing policies
Progress in molecular diagnosis and treatment of chronic mucocutaneous candidiasis
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients
Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
Overexpression of squamous cell carcinoma antigen 1 (SCCA1) in hepatitis G2 (HepG2) and Chinese hamster ovary cells can increase hepatitis B virus (HBV) binding capacity by interacting with the preS1 domain of the HBV surface antigen. However, the magnitude of increase in binding capacity was higher by several orders in the former, indicating the existence of additional factor(s) produced by HepG2 cells, which facilitates HBV attachment. Ferritin light chain (FTL) was identified as the sole high hit candidate by screening human liver cDNA library using a bacterial two-hybrid system with either preS or SCCA1 as the bait. Subsequent in vitro protein–protein interaction assays confirmed the binding activity of FTL to both preS and SCCA1, as well as the formation of triple complex preS-FTL-SCCA1, and narrowed down the binding sites on FTL. In vitro overexpression of FTL could further enhance HBV attachment in both HepG2 and Chinese hamster ovary cells, which were already overexpressing SCCA1. Importantly, in vivo co-expression of human FTL and SCCA1 in mouse liver by means of tailvein hydrodynamic injection increased serum levels of HBV surface antigen transiently 24 hours post challenge with HBV-positive human sera, and a large amount of HBV core antigen-positive hepatocytes around blood vessels could be identified by immunohistochemical staining 48 hours post challenge. The data strongly suggest that FTL and SCCA1 may serve as coreceptors in HBV cellular attachment and virus entry into hepatocytes
Using KCWI to Explore the Chemical Inhomogeneities and Evolution of J1044+0353
J1044+0353 is considered a local analog of the young galaxies that ionized
the intergalactic medium at high-redshift due to its low mass, low metallicity,
high specific star formation rate, and strong high-ionization emission lines.
We use integral field spectroscopy to trace the propagation of the starburst
across this small galaxy using Balmer emission- and absorption-line equivalent
widths and find a post-starburst population (~ 15 - 20 Myr) roughly one kpc
east of the much younger, compact starburst (~ 3 - 4 Myr). Using the direct
electron temperature method to map the O/H abundance ratio, we find similar
metallicity (1 to 3 sigma) between the starburst and post-starburst regions but
with a significant dispersion of about 0.3 dex within the latter. We also map
the Doppler shift and width of the strong emission lines. Over scales several
times the size of the galaxy, we discover a velocity gradient parallel to the
galaxy's minor axis. The steepest gradients (~ 30 $\mathrm{km \ s^{-1} \
kpc^{-1}}$) appear to emanate from the oldest stellar association. We identify
the velocity gradient as an outflow viewed edge-on based on the increased line
width and skew in a biconical region. We discuss how this outflow and the gas
inflow necessary to trigger the starburst affect the chemical evolution of
J1044+0353. We conclude that the stellar associations driving the galactic
outflow are spatially offset from the youngest association, and a chemical
evolution model with a metal-enriched wind requires a more realistic inflow
rate than a homogeneous chemical evolution model.Comment: 23 pages, 10 figure
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In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes
Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo. DOI: http://dx.doi.org/10.7554/eLife.01846.00
The Function of a Spindle Checkpoint Gene bub-1 in C. elegans Development
BACKGROUND:The serine/threonine kinase BUB1 (Budding Uninhibited by Benzimidazole 1) was originally identified in yeast as a checkpoint protein, based on its mutant's incapacity of delaying the cell cycle in response to loss of microtubules. Our understanding of its function is primarily from studies carried out in yeast S. cerevisiae. It has been shown that it is a component of the mitotic spindle checkpoint and regulates the separation of sister chromatids through its downstream molecules. However, its roles in multi-cellular organisms remain unclear. METHODS AND FINDINGS:In nematode C. elegans, rapid cell divisions primarily occur in embryos and in germline of postembryonic larvae and adults. In addition, a select set of cells undergo a few rounds of cell division postembryonically. One common phenotype associated with impaired cell division is described as Stu (Sterile and Uncoordinated) [1], [2]. We conducted a genetic screen for zygotic mutants that displayed Stu phenotype in C. elegans. We isolated seven Stu mutants that fell into five complementation groups. We report here that two mutations, FanWang5 (fw5) and FanWang8 (fw8) affect the bub-1 gene, a homolog of yeast BUB1. Both mutant alleles of fw5 and fw8 exhibited variable behavioral defects, including developmental arrest, uncoordination and sterility. The number of postembryonically born neurons in the ventral cord decreased and their axon morphology was abnormal. Also, the decrease of neurons in the ventral cord phenotype could not be suppressed by a caspase-3 loss-of-function mutant. In addition, bub-1(fw5 and fw8) mutants showed widespread effects on postembryonic development in many cell lineages. We found that bub-1 functioned maternally in several developmental lineages at the embryonic stage in C. elegans. Studies in yeast have shown that BUB1 functions as a spindle checkpoint protein by regulating the anaphase promoting complex/cyclosome (APC/C). We performed double mutant analysis and observed that bub-1 genetically interacted with several downstream genes, including fzy-1/CDC20, mat-2/APC1 and emb-27/APC6. CONCLUSIONS:Our results demonstrate a conserved role of bub-1 in cell-cycle regulation and reveal that C. elegans bub-1 is required both maternally and zygotically. Further, our genetic analysis is consistent with that the function of bub-1 in C. elegans is likely similar to its yeast and mammalian homologs
A Multi-source Data Based Analysis Framework for Urban Greenway Safety
As a green lining open space, greenways are closely related to the life of urban residents. At present, reports of crimes occurring in greenways are emerging in an endless stream. In order to explore the factors affecting greenway safety, this study, under the guidance of CPTED theory, conducts research by means of big geodata. Three representative greenways in Beijing urban area—the Northwest Tucheng greenway, Second Ring Road greenway and the Three Mountains and Five Gardens greenway—are taken as the research objects. Through the utilization of big geodata information from each platform, including street view analysis, POI analysis, and sports activity data analysis, four factors including space boundary, maintenance, public surveillance and activity support are considered comprehensively, and important influencing factors are selected to construct the analysis framework for urban greenway safety. The results showed that the greenway with high safety has the characteristics of low density of arbor shrubs, low enclosure degree of walls, low distribution density of various buildings, high traffic flow and high frequency of use. The feasibility of the analysis framework is verified by the current situation of greenway safety, so as to provide scientific and reasonable technical support for the construction of safe urban greenways
High-Dose siRNAs Upregulate Mouse Eri-1 at both Transcription and Posttranscription Levels
The eri-1 gene encodes a 3′ exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3′ untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA
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