Finding High-Dimensional D-OptimalDesigns for Logistic Models via Differential Evolution

D-optimal designs are frequently used in controlled experiments to obtain the most accurateestimate of model parameters at minimal cost. Finding them can be a challenging task, especially whenthere are many factors in a nonlinear model. As the number of factors becomes large and interact withone another, there are many more variables to optimize and the D-optimal design problem becomes highdimensionaland non-separable. Consequently, premature convergence issues arise. Candidate solutions gettrapped in local optima and the classical gradient-based optimization approaches to search for the D-optimaldesigns rarely succeed. We propose a specially designed version of differential evolution (DE) which is arepresentative gradient-free optimization approach to solve such high-dimensional optimization problems.The proposed specially designed DE uses a new novelty-based mutation strategy to explore the variousregions in the search space. The exploration of the regions will be carried out differently from the previouslyexplored regions and the diversity of the population can be preserved. The proposed novelty-based mutationstrategy is collaborated with two common DE mutation strategies to balance exploration and exploitationat the early or medium stage of the evolution. Additionally, we adapt the control parameters of DE as theevolution proceeds. Using logistic models with several factors on various design spaces as examples, oursimulation results show our algorithm can find D-optimal designs efficiently and the algorithm outperformsits competitors. As an application, we apply our algorithm and re-design a 10-factor car refueling experimentwith discrete and continuous factors and selected pairwise interactions. Our proposed algorithm was able toconsistently outperform the other algorithms and find a more efficient D-optimal design for the problem

Scalable surface code decoders with parallelization in time

Fast classical processing is essential for most quantum fault-tolerance architectures. We introduce a sliding-window decoding scheme that provides fast classical processing for the surface code through parallelism. Our scheme divides the syndromes in spacetime into overlapping windows along the time direction, which can be decoded in parallel with any inner decoder. With this parallelism, our scheme can solve the decoding throughput problem as the code scales up, even if the inner decoder is slow. When using min-weight perfect matching and union-find as the inner decoders, we observe circuit-level thresholds of $0.68\%$ and $0.55\%$, respectively, which are almost identical to $0.70\%$ and $0.55\%$ for the batch decoding.Comment: Main text: 6 pages, 3 figures. Supplementary material: 18 pages, 14 figures. V2: added data and updated general formalis

Free-style and Fast 3D Portrait Synthesis

Efficiently generating a free-style 3D portrait with high quality and consistency is a promising yet challenging task. The portrait styles generated by most existing methods are usually restricted by their 3D generators, which are learned in specific facial datasets, such as FFHQ. To get a free-style 3D portrait, one can build a large-scale multi-style database to retrain the 3D generator, or use a off-the-shelf tool to do the style translation. However, the former is time-consuming due to data collection and training process, the latter may destroy the multi-view consistency. To tackle this problem, we propose a fast 3D portrait synthesis framework in this paper, which enable one to use text prompts to specify styles. Specifically, for a given portrait style, we first leverage two generative priors, a 3D-aware GAN generator (EG3D) and a text-guided image editor (Ip2p), to quickly construct a few-shot training set, where the inference process of Ip2p is optimized to make editing more stable. Then we replace original triplane generator of EG3D with a Image-to-Triplane (I2T) module for two purposes: 1) getting rid of the style constraints of pre-trained EG3D by fine-tuning I2T on the few-shot dataset; 2) improving training efficiency by fixing all parts of EG3D except I2T. Furthermore, we construct a multi-style and multi-identity 3D portrait database to demonstrate the scalability and generalization of our method. Experimental results show that our method is capable of synthesizing high-quality 3D portraits with specified styles in a few minutes, outperforming the state-of-the-art.Comment: project website: https://tianxiangma.github.io/FF3

IscA/SufA paralogues are required for the [4Fe-4S] cluster assembly in enzymes of multiple physiological pathways in Escherichia coli under aerobic growth conditions

IscA/SufA paralogues are the members of the iron-sulfur cluster assembly machinery in Escherichia coli. Whereas deletion of either IscA or SufA has only a mild effect on cell growth, deletion of both IscA and SufA results in a null-growth phenotype in minimal medium under aerobic growth conditions. Here we report that cell growth of the iscA/sufA double mutant (E. coli strain in which both iscA and sufA had been in-frame-deleted) can be partially restored by supplementing with BCAAs (branched-chain amino acids) and thiamin. We further demonstrate that deletion of IscA/SufA paralogues blocks the [4Fe-4S] cluster assembly in IlvD (dihydroxyacid dehydratase) of the BCAA biosynthetic pathway in E. coli cells under aerobic conditions and that addition of the iron-bound IscA/SufA efficiently promotes the [4Fe-4S] cluster assembly in IlvD and restores the enzyme activity in vitro, suggesting that IscA/SufA may act as an iron donor for the [4Fe-4S] cluster assembly under aerobic conditions. Additional studies reveal that IscA/SufA are also required for the [4Fe-4S] cluster assembly in enzyme ThiC of the thiamin-biosynthetic pathway, aconitase B of the citrate acid cycle and endonuclease III of the DNA-base-excision-repair pathway in E. coli under aerobic conditions. Nevertheless, deletion of IscA/SufA does not significantly affect the [2Fe-2S] cluster assembly in the redox transcription factor SoxR, ferredoxin and the siderophore-iron reductase FhuF. The results suggest that the biogenesis of the [4Fe-4S] clusters and the [2Fe-2S] clusters may have distinct pathways and that IscA/SufA paralogues are essential for the [4Fe-4S] cluster assembly, but are dispensable for the [2Fe-2S] cluster assembly in E. coli under aerobic conditions. © The Authors Journal compilation

Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model.

PurposeThe goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model.Materials and methodsA colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&E staining and immunohistochemical staining were used for histological analysis.ResultsAll three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM + PAZ + FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOX mouse model suggesting inhibition of lymphangiogenesis.ConclusionOur results suggest that the combination of TEM + PAZ + FOLFOX has clinical potential for colorectal cancer patient

sasdim: self-adaptive noise scaling diffusion model for spatial time series imputation

Spatial time series imputation is critically important to many real applications such as intelligent transportation and air quality monitoring. Although recent transformer and diffusion model based approaches have achieved significant performance gains compared with conventional statistic based methods, spatial time series imputation still remains as a challenging issue due to the complex spatio-temporal dependencies and the noise uncertainty of the spatial time series data. Especially, recent diffusion process based models may introduce random noise to the imputations, and thus cause negative impact on the model performance. To this end, we propose a self-adaptive noise scaling diffusion model named SaSDim to more effectively perform spatial time series imputation. Specially, we propose a new loss function that can scale the noise to the similar intensity, and propose the across spatial-temporal global convolution module to more effectively capture the dynamic spatial-temporal dependencies. Extensive experiments conducted on three real world datasets verify the effectiveness of SaSDim by comparison with current state-of-the-art baselines

Iron-binding activity of human iron-sulfur cluster assembly protein hIscA1

A human homologue of the iron-sulfur cluster assembly protein IscA (hIscA1) has been cloned and expressed in Escherichia coli cells. The UV-visible absorption and EPR (electron paramagnetic resonance) measurements reveal that hIscA1 purified from E. coli cells contains a mononuclear iron centre and that the iron binding in hIscA1 expressed in E. coli cells can be furthermodulated by the iron content in the cell growth medium. Additional studies show that purified hIscA1 binds iron with an iron association constant of approx. 2×1019 M-1, and that the iron-bound hIscA1 is able to provide the iron for the iron-sulfur cluster assembly in a proposed scaffold protein, IscU of E. coli, in vitro. The complementation experiments indicate that hIscA1 can partially substitute for IscA in restoring the cell growth of E. coli in the M9 minimal medium under aerobic conditions. The results suggest that hIscA1, like E. coli IscA, is an iron-binding protein that may act as an iron chaperone for biogenesis of iron-sulfur clusters. © The Authors

Competition of zinc ion for the [2Fe-2S] cluster binding site in the diabetes drug target protein mitoNEET

Human mitochondrial protein mitoNEET is a novel target of type II diabetes drug pioglitazone, and contains a redox active [2Fe-2S] cluster that is hosted by a unique ligand arrangement of three cysteine and one histidine residues. Here we report that zinc ion can compete for the [2Fe-2S] cluster binding site in human mitoNEET and potentially modulate the physiological function of mitoNEET. When recombinant mitoNEET is expressed in Escherichia coli cells grown in M9 minimal media, purified mitoNEET contains very little or no iron-sulfur clusters. Addition of exogenous iron or zinc ion in the media produces mitoNEET bound with a [2Fe-2S] cluster or zinc, respectively. Mutations of the amino acid residues that hosting the [2Fe-2S] cluster in mitoNEET diminish the zinc binding activity, indicating that zinc ion and the [2Fe-2S] cluster may share the same binding site in mitoNEET. Finally, excess zinc ion effectively inhibits the [2Fe-2S] cluster assembly in mitoNEET in E. coli cells, suggesting that zinc ion may impede the function of mitoNEET by blocking the [2Fe-2S] cluster assembly in the protein. Copyright © Springer Science+Business Media, LLC. 2012

Deletion of the proposed iron chaperones IscA/SufA results in accumulation of a red intermediate cysteine desulfurase IscS in Escherichia coli

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. In Escherichia coli, sulfur in iron-sulfur clusters is primarily derived from L-cysteine via the cysteine desulfurase IscS. However, the iron donor for iron-sulfur cluster assembly remains elusive. Previous studies have shown that, among the iron-sulfur cluster assembly proteins in E. coli, IscA has a unique and strong iron-binding activity and that the iron-bound IscA can efficiently provide iron for iron-sulfur cluster assembly in proteins in vitro, indicating that IscA may act as an iron chaperone for iron-sulfur cluster biogenesis. Here we report that deletion of IscA and its paralog SufA in E. coli cells results in the accumulation of a red-colored cysteine desulfurase IscS under aerobic growth conditions. Depletion of intracellular iron using a membrane-permeable iron chelator, 2,2′-dipyridyl, also leads to the accumulation of red IscS in wild-type E. coli cells, suggesting that the deletion of IscA/SufA may be emulated by depletion of intracellular iron. Purified red IscS has an absorption peak at 528 nm in addition to the peak at 395 nm of pyridoxal 5′-phosphate. When red IscS is oxidized by hydrogen peroxide, the peak at 528 nm is shifted to 510 nm, which is similar to that of alanine-quinonoid intermediate in cysteine desulfurases. Indeed, red IscS can also be produced in vitro by incubating wild-type IscS with excess L-alanine and sulfide. The results led us to propose that deletion of IscA/SufA may disrupt the iron delivery for iron-sulfur cluster biogenesis, therefore impeding sulfur delivery by IscS, and result in the accumulation of red IscS in E. coli cells

Iron and zinc binding activity of Escherichia coli topoisomerase I homolog YrdD

YrdD, a homolog of the C-terminal zinc-binding region of Escherichia coli topoisomerase I, is highly conserved among proteobacteria and enterobacteria. However, the function of YrdD remains elusive. Here we report that YrdD purified from E. coli cells grown in LB media contains both zinc and iron. Supplement of exogenous zinc in the medium abolishes the iron binding of YrdD in E. coli cells, indicating that iron and zinc may compete for the same metal binding sites in the protein. While the zinc-bound YrdD is able to bind single-stranded (ss) DNA and protect ssDNA from the DNase I digestion in vitro, the iron-bound YrdD has very little or no binding activity for ssDNA, suggesting that the zinc-bound YrdD may have an important role in DNA repair by interacting with ssDNA in cells. © 2014 Springer Science+Business Media