3,198 research outputs found
Mechanism of glycan receptor recognition and specificity switch for avian, swine, and human adapted influenza virus hemagglutinins: a molecular dynamics perspective.
Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (alpha-2,3 linkage) and LSTc (alpha-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified approximately 30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development
Consistency and Accuracy of CelebA Attribute Values
We report the first systematic analysis of the experimental foundations of facial attribute classification.Two annotators independently assigning attribute values shows that only 12 of 40 common attributes are assigned values with >= 95% consistency, and three (high cheekbones, pointed nose, oval face) have essentially random consistency. Of 5,068 duplicate face appearances in CelebA, attributes have contradicting values on from 10 to 860 of the 5,068 duplicates. Manual audit of a subset of CelebA estimates error rates as high as 40% for (no beard=false), even though the labeling consistency experiment indicates that no beard could be assigned with >= 95% consistency. Selecting the mouth slightly open (MSO) for deeper analysis, we estimate the error rate for (MSO=true) at about 20% and (MSO=false) at about 2%. A corrected version of the MSO attribute values enables learning a model that achieves higher accuracy than previously reported for MSO. Corrected values for CelebA MSO are available at https:// github.com/ HaiyuWu/ CelebAMSO
Our Deep CNN Face Matchers Have Developed Achromatopsia
Modern deep CNN face matchers are trained on datasets containing color
images. We show that such matchers achieve essentially the same accuracy on the
grayscale or the color version of a set of test images. We then consider
possible causes for deep CNN face matchers ``not seeing color''. Popular
web-scraped face datasets actually have 30 to 60\% of their identities with one
or more grayscale images. We analyze whether this grayscale element in the
training set impacts the accuracy achieved, and conclude that it does not.
Further, we show that even with a 100\% grayscale training set, comparable
accuracy is achieved on color or grayscale test images. Then we show that the
skin region of an individual's images in a web-scraped training set exhibit
significant variation in their mapping to color space. This suggests that
color, at least for web-scraped, in-the-wild face datasets, carries limited
identity-related information for training state-of-the-art matchers. Finally,
we verify that comparable accuracy is achieved from training using
single-channel grayscale images, implying that a larger dataset can be used
within the same memory limit, with a less computationally intensive early
layer
The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion
Objective: A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion. Methods: Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (n = 82) showed significantly elevated MD acutely after injury (<48 h), at an asymptomatic time point, 7 days post-return to play (RTP), and 6 months relative to controls (n = 69). The relationship between MD in the identified ROI and likelihood of sustaining a subsequent concussion over a 1-year period was examined with a binary logistic regression (re-injured, yes/no). Results: Eleven of 82 concussed athletes (13.4%) sustained a second concussion within 12 months of initial injury. Mean MD at 7 days post-RTP was significantly higher in those athletes who went on to sustain a repeat concussion within 1 year of initial injury than those who did not (p = 0.048; d = 0.75). In this underpowered sample, the relationship between MD at 7 days post-RTP and likelihood of sustaining a secondary injury approached significance [χ2 (1) = 4.17, p = 0.057; B = 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07]. Conclusions: These preliminary findings raise the hypothesis that persistent signal abnormalities in diffusion imaging metrics at RTP following concussion may be predictive of a repeat concussion. This may reflect a window of cerebral vulnerability or increased susceptibility following concussion, though understanding the clinical significance of these findings requires further study
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Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS and familial ALS with GGGGCC repeat expansion in the C9orf72 gene, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability
A Review of Target Mass Corrections
With recent advances in the precision of inclusive lepton--nuclear scattering
experiments, it has become apparent that comparable improvements are needed in
the accuracy of the theoretical analysis tools. In particular, when extracting
parton distribution functions in the large-x region, it is crucial to correct
the data for effects associated with the nonzero mass of the target. We present
here a comprehensive review of these target mass corrections (TMC) to structure
functions data, summarizing the relevant formulas for TMCs in electromagnetic
and weak processes. We include a full analysis of both hadronic and partonic
masses, and trace how these effects appear in the operator product expansion
and the factorized parton model formalism, as well as their limitations when
applied to data in the x->1 limit. We evaluate the numerical effects of TMCs on
various structure functions, and compare fits to data with and without these
corrections.Comment: 41 pages, 13 figures; minor updates to match published versio
Direct Production of Furfural in One-pot Fashion from Raw Biomass Using Brønsted Acidic Ionic Liquids
The conversion of raw biomass into C5-sugars and furfural was demonstrated with the one-pot method using Brønsted acidic ionic liquids (BAILs) without any mineral acids or metal halides. Various BAILs were synthesized and characterized using NMR, FT-IR, TGA, and CHNS microanalysis and were used as the catalyst for raw biomass conversion. The remarkably high yield (i.e. 88%) of C5 sugars from bagasse can be obtained using 1-methyl-3(3-sulfopropyl)-imidazolium hydrogen sulfate ([C 3 SO 3 HMIM][HSO 4 ]) BAIL catalyst in a water medium. Similarly, the [C 3 SO 3 HMIM][HSO 4 ] BAIL also converts the bagasse into furfural with very high yield (73%) in one-pot method using a water/toluene biphasic solvent system
Out-of-Plane Piezoelectricity and Ferroelectricity in Layered α-In2Se3 Nanoflakes
Piezoelectric and ferroelectric properties in the two-dimensional (2D) limit are highly desired for nanoelectronic, electromechanical, and optoelectronic applications. Here we report the first experimental evidence of out-of-plane piezoelectricity and ferroelectricity in van der Waals layered α-In2Se3 nanoflakes. The noncentrosymmetric R3m symmetry of the α-In2Se3 samples is confirmed by scanning transmission electron microscopy, second-harmonic generation, and Raman spectroscopy measurements. Domains with opposite polarizations are visualized by piezo-response force microscopy. Single-point poling experiments suggest that the polarization is potentially switchable for α-In2Se3 nanoflakes with thicknesses down to ∼10 nm. The piezotronic effect is demonstrated in two-terminal devices, where the Schottky barrier can be modulated by the strain-induced piezopotential. Our work on polar α-In2Se3, one of the model 2D piezoelectrics and ferroelectrics with simple crystal structures, shows its great potential in electronic and photonic applications
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BioC: a minimalist approach to interoperability for biomedical text processing
A vast amount of scientific information is encoded in natural language text, and the quantity of such text has become so great that it is no longer economically feasible to have a human as the first step in the search process. Natural language processing and text mining tools have become essential to facilitate the search for and extraction of information from text. This has led to vigorous research efforts to create useful tools and to create humanly labeled text corpora, which can be used to improve such tools. To encourage combining these efforts into larger, more powerful and more capable systems, a common interchange format to represent, store and exchange the data in a simple manner between different language processing systems and text mining tools is highly desirable. Here we propose a simple extensible mark-up language format to share text documents and annotations. The proposed annotation approach allows a large number of different annotations to be represented including sentences, tokens, parts of speech, named entities such as genes or diseases and relationships between named entities. In addition, we provide simple code to hold this data, read it from and write it back to extensible mark-up language files and perform some sample processing. We also describe completed as well as ongoing work to apply the approach in several directions. Code and data are available at http://bioc.sourceforge.net/. Database URL: http://bioc.sourceforge.net
BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.
Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-β (TGF-β) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-β signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy
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