522 research outputs found
Protein structure generation via folding diffusion
The ability to computationally generate novel yet physically foldable protein
structures could lead to new biological discoveries and new treatments
targeting yet incurable diseases. Despite recent advances in protein structure
prediction, directly generating diverse, novel protein structures from neural
networks remains difficult. In this work, we present a new diffusion-based
generative model that designs protein backbone structures via a procedure that
mirrors the native folding process. We describe protein backbone structure as a
series of consecutive angles capturing the relative orientation of the
constituent amino acid residues, and generate new structures by denoising from
a random, unfolded state towards a stable folded structure. Not only does this
mirror how proteins biologically twist into energetically favorable
conformations, the inherent shift and rotational invariance of this
representation crucially alleviates the need for complex equivariant networks.
We train a denoising diffusion probabilistic model with a simple transformer
backbone and demonstrate that our resulting model unconditionally generates
highly realistic protein structures with complexity and structural patterns
akin to those of naturally-occurring proteins. As a useful resource, we release
the first open-source codebase and trained models for protein structure
diffusion
ASL Citizen: A Community-Sourced Dataset for Advancing Isolated Sign Language Recognition
Sign languages are used as a primary language by approximately 70 million
D/deaf people world-wide. However, most communication technologies operate in
spoken and written languages, creating inequities in access. To help tackle
this problem, we release ASL Citizen, the first crowdsourced Isolated Sign
Language Recognition (ISLR) dataset, collected with consent and containing
83,399 videos for 2,731 distinct signs filmed by 52 signers in a variety of
environments. We propose that this dataset be used for sign language dictionary
retrieval for American Sign Language (ASL), where a user demonstrates a sign to
their webcam to retrieve matching signs from a dictionary. We show that
training supervised machine learning classifiers with our dataset advances the
state-of-the-art on metrics relevant for dictionary retrieval, achieving 63%
accuracy and a recall-at-10 of 91%, evaluated entirely on videos of users who
are not present in the training or validation sets. An accessible PDF of this
article is available at the following link:
https://aashakadesai.github.io/research/ASLCitizen_arxiv_updated.pd
Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites
Peer reviewedPublisher PD
Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family
Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al
BAs and boride III-V alloys
Boron arsenide, the typically-ignored member of the III-V arsenide series
BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma
conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an
X_1c-like indirect band gap, and its bond charge is distributed almost equally
on the two atoms in the unit cell, exhibiting nearly perfect covalency. The
reasons for these are tracked down to the anomalously low atomic p orbital
energy in the boron and to the unusually strong s-s repulsion in BAs relative
to most other III-V compounds. We find unexpected valence band offsets of BAs
with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is
significantly higher than that of AlAs, despite the much smaller bond length of
BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects
result from the unusually strong mixing of the cation and anion states at the
VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and
composition-independent band gap bowing. This means that while addition of
small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of
boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the
conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing
enthalpies which are smaller than in GaN-GaAs alloys. The unique features of
boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for
publication in Phys. Rev. B. Scheduled to appear Oct. 15 200
Optimal Renormalization Scale and Scheme for Exclusive Processes
We use the BLM method to fix the renormalization scale of the QCD coupling in
exclusive hadronic amplitudes such as the pion form factor and the
photon-to-pion transition form factor at large momentum transfer.
Renormalization-scheme-independent commensurate scale relations are established
which connect the hard scattering subprocess amplitudes that control exclusive
processes to other QCD observables such as the heavy quark potential and the
electron-positron annihilation cross section. The commensurate scale relation
connecting the heavy quark potential, as determined from lattice gauge theory,
to the photon-to-pion transition form factor is in excellent agreement with
data assuming that the pion distribution amplitude is
close to its asymptotic form . We also reproduce the
scaling and normalization of the data at large
momentum transfer. Because the renormalization scale is small, we argue that
the effective coupling is nearly constant, thus accounting for the nominal
scaling behavior of the data. However, the normalization of the space-like pion
form factor obtained from electroproduction experiments is
somewhat higher than that predicted by the corresponding commensurate scale
relation. This discrepancy may be due to systematic errors introduced by the
extrapolation of the electroproduction data to the
pion pole.Comment: 22 pages, Latex, 7 Latex figures. Several references added,
discussion of scale fixing revised for clarity. Final version to appear in
Phys. Rev.
Transcriptome profiling of grapevine seedless segregants during berry development reveals candidate genes associated with berry weight
Indexación: Web of Science; PubMedBackground
Berry size is considered as one of the main selection criteria in table grape breeding programs. However, this is a quantitative and polygenic trait, and its genetic determination is still poorly understood. Considering its economic importance, it is relevant to determine its genetic architecture and elucidate the mechanisms involved in its expression. To approach this issue, an RNA-Seq experiment based on Illumina platform was performed (14 libraries), including seedless segregants with contrasting phenotypes for berry weight at fruit setting (FST) and 6–8 mm berries (B68) phenological stages.
Results
A group of 526 differentially expressed (DE) genes were identified, by comparing seedless segregants with contrasting phenotypes for berry weight: 101 genes from the FST stage and 463 from the B68 stage. Also, we integrated differential expression, principal components analysis (PCA), correlations and network co-expression analyses to characterize the transcriptome profiling observed in segregants with contrasting phenotypes for berry weight. After this, 68 DE genes were selected as candidate genes, and seven candidate genes were validated by real time-PCR, confirming their expression profiles.
Conclusions
We have carried out the first transcriptome analysis focused on table grape seedless segregants with contrasting phenotypes for berry weight. Our findings contributed to the understanding of the mechanisms involved in berry weight determination. Also, this comparative transcriptome profiling revealed candidate genes for berry weight which could be evaluated as selection tools in table grape breeding programs.http://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-016-0789-
Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia.
Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics
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