52 research outputs found
Free-Bloom: Zero-Shot Text-to-Video Generator with LLM Director and LDM Animator
Text-to-video is a rapidly growing research area that aims to generate a
semantic, identical, and temporal coherence sequence of frames that accurately
align with the input text prompt. This study focuses on zero-shot text-to-video
generation considering the data- and cost-efficient. To generate a
semantic-coherent video, exhibiting a rich portrayal of temporal semantics such
as the whole process of flower blooming rather than a set of "moving images",
we propose a novel Free-Bloom pipeline that harnesses large language models
(LLMs) as the director to generate a semantic-coherence prompt sequence, while
pre-trained latent diffusion models (LDMs) as the animator to generate the high
fidelity frames. Furthermore, to ensure temporal and identical coherence while
maintaining semantic coherence, we propose a series of annotative modifications
to adapting LDMs in the reverse process, including joint noise sampling,
step-aware attention shift, and dual-path interpolation. Without any video data
and training requirements, Free-Bloom generates vivid and high-quality videos,
awe-inspiring in generating complex scenes with semantic meaningful frame
sequences. In addition, Free-Bloom is naturally compatible with LDMs-based
extensions.Comment: NeurIPS 2023; Project available at:
https://github.com/SooLab/Free-Bloo
Modeling Method for Increased Precision and Scope of Directly Measurable Fluxes at a Genome-Scale
Metabolic flux analysis (MFA) is
considered to be the gold standard
for determining the intracellular flux distribution of biological
systems. The majority of work using MFA has been limited to core models
of metabolism due to challenges in implementing genome-scale MFA and
the undesirable trade-off between increased scope and decreased precision
in flux estimations. This work presents a tunable workflow for expanding
the scope of MFA to the genome-scale without trade-offs in flux precision.
The genome-scale MFA model presented here, iDM2014, accounts for 537
net reactions, which includes the core pathways of traditional MFA
models and also covers the additional pathways of purine, pyrimidine,
isoprenoid, methionine, riboflavin, coenzyme A, and folate, as well
as other biosynthetic pathways. When evaluating the iDM2014 using
a set of measured intracellular intermediate and cofactor mass isotopomer
distributions (MIDs), it was found that
a total of 232 net fluxes of central and peripheral metabolism could
be resolved in the <i>E. coli</i> network. The increase
in scope was shown to cover the full biosynthetic route to an expanded
set of bioproduction pathways, which should facilitate applications
such as the design of more complex bioprocessing strains and aid in
identifying new antimicrobials. Importantly, it was found that there
was no loss in precision of core fluxes when compared to a traditional
core model, and additionally there was an overall increase in precision
when considering all observable reactions
Evolution of gene knockout strains of <i>E-coli</i> reveal regulatory architectures governed by metabolism
The function of metabolic genes in the context of regulatory networks is not well understood. Here, the authors investigate the adaptive responses of E. coli after knockout of metabolic genes and highlight the influence of metabolite levels in the evolution of regulatory function
Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in <i>Escherichia coli pgi</i> Knockout Evolutions
A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory functions of the lost gene. The pgi gene, whose product catalyzes the second step in glycolysis, was deleted in a growth-optimized Escherichia coli K-12 MG1655 strain. The initial knockout (KO) strain exhibited an 80% drop in growth rate that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi-omic data sets showed that the loss of pgi substantially shifted pathway usage, leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.IMPORTANCE A mechanistic understanding of how microbes are able to overcome the loss of a gene through regulatory and metabolic changes is not well understood. Eight independent adaptive laboratory evolution (ALE) experiments with pgi knockout strains resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed
Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone
α-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to α-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (Δψm). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents
Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone
α-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to α-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (ÎÏm). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents
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