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Unsupervised domain adaptation (UDA) typically carries out knowledge transfer from a label-rich source domain to an unlabeled target domain by adversarial learning. In principle, existing UDA approaches mainly focus on the global distribution alignment between domains while ignoring the intrinsic local distribution properties. Motivated by this observation, we propose an end-to-end structure-conditioned adversarial learning scheme (SCAL) that is able to preserve the intra-class compactness during domain distribution alignment. By using local structures as structure-aware conditions, the proposed scheme is implemented in a structure-conditioned adversarial learning pipeline. The above learning procedure is iteratively performed by alternating between local structures establishment and structure-conditioned adversarial learning. Experimental results demonstrate the effectiveness of the proposed scheme in UDA scenarios. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rational design of nanoparticles distributed inside and outside the CNTs. • Nanoconfined TiO 2 generate radical species. • Surface loading Co 3 O 4 generate non-radical species-1O 2. • TiO 2 -in-CNT/Co 3 O 4 system has excellent anti-interference and stability. • TiO 2 -in-CNT/Co 3 O 4 can degrade ECs in broad-spectrum. The efficient activation of peroxymonosulfate for degrading emerging contaminants has become a focal point in recent decades, emphasizing the development of novel materials and efficient strategies for high-performance degradation. This study explores a spatial confinement strategy, where TiO 2 is confined inside carbon nanotubes with Co 3 O 4 loading outside, is performed to prepare the nano-confined composite TiO 2 -in-CNT/Co 3 O 4. Norfloxacin is chosen as the primary target pollutant, revealing a degradation rate exceeding 97 % within 30 min. The non-radical 1O 2 species were confirmed to be generated in nano-confined catalyst, but not observed in the control non-confined catalyst. Additionally, the quantity of original radical active species significantly increases in nano-confined catalyst compared to non-confined catalyst. TiO 2 -in-CNT/Co 3 O 4 has excellent reusability and application universality. Wonderful stability is observed in real water and anti-ion interference experiments, highlighting its robust stability. Experimental and DFT calculation results also demonstrate that the spatial confinement strategy prevents nanoparticle aggregation, accelerates electron transfer efficiency, and promotes the cycling of Co2+/Co3+ electron pairs. This work provides insights into the regulation of confined effects in activating PMS and offers a feasible strategy for the synergistic activation of PMS for water environment remediation through a radical and non-radical mixed mechanism. [ABSTRACT FROM AUTHOR]

We define a three-dimensional quantum theory of gravity as the holographic dual of the Liouville conformal field theory. The theory is consistent and unitary by definition. The corresponding theory of gravity with negative cosmological constant has peculiar properties. The quantum theory has no normalizable A d S 3 vacuum. The model contains primary black holes with zero spin. All states can be interpreted as BTZ geometries dressed with boundary gravitons. There is a unique universal interaction between these states consistent with unitarity and the conformal symmetry of the model. This theory of gravity, though conceptually isolated from other models of quantum gravity, is worth scrutinizing. [ABSTRACT FROM AUTHOR]

BACKGROUND: The polychromatic X-rays generated by a linear accelerator (Linac) often result in noticeable hardening artifacts in images, posing a significant challenge to accurate defect identification. To address this issue, a simple yet effective approach is to introduce filters at the radiation source outlet. However, current methods are often empirical, lacking scientifically sound metrics. OBJECTIVE: This study introduces an innovative filter design method that optimizes filter performance by balancing the impact of ray intensity and energy on image quality. MATERIALS AND METHODS: Firstly, different spectra under various materials and thicknesses of filters were obtained using GEometry ANd Tracking (Geant4) simulation. Subsequently, these spectra and their corresponding incident photon counts were used as input sources to generate different reconstructed images. By comprehensively comparing the intensity differences and noise in images of defective and non-defective regions, along with considering hardening indicators, the optimal filter was determined. RESULTS: The optimized filter was applied to a Linac-based X-ray computed tomography (CT) detection system designed for identifying defects in graphite materials within high-temperature gas-cooled reactor (HTR), with defect dimensions of 2 mm. After adding the filter, the hardening effect reduced by 22%, and the Defect Contrast Index (DCI) reached 3.226. CONCLUSION: The filter designed based on the parameters of Average Difference (AD) and Defect Contrast Index (DCI) can effectively improve the quality of defect images. [ABSTRACT FROM AUTHOR]

In order to establish the combined prediction model of milling noise based on force-thermal-vibration multi-feature fusion, a simultaneous milling noise-vibration-thermal-force test system was established. Based on the gray correlation theory and test data, the relationship between milling sound pressure and milling parameters, milling vibration, milling force, and milling thermal was analyzed. Based on the least square method, three single prediction models of milling sound pressure level for three-directional vibration, milling thermal, and three-directional milling force were established. Then, the weight coefficients of the combined model are determined by the standard errors of the three single models, and the linear combination model of the mean square root of milling sound pressure level expressed by the three single prediction models and the corresponding weight coefficients was established. The correlation coefficient of the combined prediction model of sound pressure is 0.95, which is larger than the correlation coefficient of three single prediction models. It shows that the combined prediction model of sound pressure level with multiple features can better predict milling noise and provide theoretical guidance for milling tool condition monitoring. [ABSTRACT FROM AUTHOR]

To satisfy the stringent requirements for computational resources in the field of real-time semantic segmentation, most approaches focus on the hand-crafted design of light-weight segmentation networks. To enjoy the ability of model auto-design, Neural Architecture Search (NAS) has been introduced to search for the optimal building blocks of networks automatically. However, the network depth, downsampling strategy, and feature aggregation method are still set in advance and nonadjustable during searching. Moreover, these key properties are highly correlated and essential for a remarkable real-time segmentation model. In this paper, we propose a joint search framework, called AutoRTNet, to automate all the aforementioned key properties in semantic segmentation. Specifically, we propose hyper-cells to jointly decide the network depth and the downsampling strategy via a novel cell-level pruning process. Furthermore, we propose an aggregation cell to achieve automatic multi-scale feature aggregation. Extensive experimental results on Cityscapes and CamVid datasets demonstrate that the proposed AutoRTNet achieves the new state-of-the-art trade-off between accuracy and speed. Notably, our AutoRTNet achieves 73.9% mIoU on Cityscapes and 110.0 FPS on an NVIDIA TitanXP GPU card with input images at a resolution of 768 × 1536 . [ABSTRACT FROM AUTHOR]

CO and HCHO are the main pyrolysis gases in long-term running dry-type reactors, and thus the diagnosis of thermal insulation faults inside such devices can be realized by sensing these gases. In this paper, a single Au atom-decorated WS2 (Au-WS2) monolayer is proposed as an original sensing material for CO or HCHO detection to evaluate the operation status of dry-type reactors. It was found that the Au atom prefers to be adsorbed at the top of the S atom of the pristine WS2 monolayer, wherein the binding force is calculated as −3.12 eV. The Au-WS2 monolayer behaves by chemisorption upon the introduction of CO and HCHO molecules, with the adsorption energies of −0.82 and −1.01 eV, respectively. The charge density difference was used to analyze the charge-transfer and bonding behaviors in the gas adsorptions, and the analysis of density of state as well as band structure indicate gas-sensing mechanisms. As calculated, the sensing responses of the Au-WS2 monolayer upon CO and HCHO molecule introduction were 58.7% and −74.4%, with recovery times of 0.01 s and 11.86 s, respectively. These findings reveal the favorable potential of the Au-WS2 monolayer to be a reusable and room-temperature sensing candidate for CO and HCHO detections. Moreover, the work function of the Au-WS2 monolayer was decreased by 13.0% after the adsorption of CO molecules, while it increased by 1.2% after the adsorption of HCHO molecules, which implies its possibility to be a work-function-based gas sensor for CO detection. This theoretical report paves the way for further investigations into WS2-based gas sensors in some other fields, and it is our hope that our findings can stimulate more reports on novel gas-sensing materials for application in evaluating the operation conditions of dry-type reactors. [ABSTRACT FROM AUTHOR]

The effects of the ordered and disordered arrangements of elements on radiation-induced defects production and evolution in NiFe alloys were investigated through atomistic simulations. Results present a sluggish evolution of the overall microstructure in ordered L1 0 NiFe. Although the disordered phase has fewer Frankel pair accumulation in cascade simulation attributed to the low thermal conductivity reduced by the intrinsic chemical disorder, the difference is negligible when PKA energy increases because of the direct formation of clusters. Interstitial diffusion is restricted in the ordered phase, where Ni and Fe layers are alternately arranged. This condition delays interstitials accumulation and leads to the formation of more Shockley partial loops rather than Frank loops which favor in the disordered phase. The higher stacking fault energy in the ordered phase renders it difficult to form stacking fault tetrahedra [ABSTRACT FROM AUTHOR]

[Display omitted] • Cd2+ can be fast qualitatively/quantitatively detect and adsorbed to be removed. • Tetracycline can be effectively degraded to be removed by visible light irradiation. • The above two performances can be simultaneously achieved by using TiO 2 /DAT. • TiO 2 /DAT is highly potential to treat complex pollution thanks to its trifunction. Waste water is difficult to treat, mainly because of the co-existence of organic and inorganic contaminants, attracting much attention. Herein, a novel nanohybrid of TiO 2 /dicarboxylate 1,5-diphenyl-3-thiocarbazone(III) (denoted as TiO 2 /DAT) was facilely synthesized. TiO 2 /DAT was used to treat the waste water with the co-existence of tetracycline (TC) and Cd2+. The results indicated that TiO 2 /DAT can qualitatively/quantitatively detect Cd2+ via colorimetry, and the Cd2+ adsorption can boost the TC degradation by TiO 2 /DAT. It was found that the co-existence of TC does not affect the detection and adsorption of Cd2+. Furthermore, whether Cd2+ being adsorbed in advance or co-existent with TC, the TC degradation manners over TiO 2 /DAT were similar. A reasonable deduction for these phenomena is that Cd2+ was adsorbed by TiO 2 /DAT before TC, which was confirmed by density functional theory (DFT) calculations. So TC and Cd2+ will not compete the surface active sites of TiO 2 /DAT when treated simultaneously by TiO 2 /DAT, and that is why TiO 2 /DAT can effectively treat TC and Cd2+ co-existent waste water. Upon TiO 2 /DAT, the treating strategies of detection, adsorption and degradation are combined into one functional material. This one stone three birds strategy can simplify the treating process of complex pollution systems, exhibiting highly promising in practical applications. [ABSTRACT FROM AUTHOR]

Replacing petrochemicals with compounds from bio-based manufacturing processes remains an important part of the global effort to move towards a sustainable future. However, achieving economic viability requires both optimized cell factories and innovative processes. Here, we address this challenge by developing a fermentation platform, which enables two concurrent fermentations in one bioreactor. We first construct a xylitol producing Escherichia coli strain in which CRISPRi-mediated gene silencing is used to switch the metabolism from aerobic to anaerobic, even when the bacteria are under oxic conditions. The switch also decouples growth from production, which further increases the yield. The strain produces acetate as a byproduct, which is subsequently metabolized under oxic conditions by a secondary E. coli strain. Through constraint-based metabolic modelling this strain is designed to co-valorize glucose and the excreted acetate to a secondary product. This unique syntrophic consortium concept facilitates the implementation of "two fermentations in one go", where the concurrent fermentation displays similar titers and productivities as compared to two separate single strain fermentations., (© 2024. The Author(s).)

Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan. To study the effects of targeted mutations on an endogenous level, we generated and characterized an iPSC derived model for venous malformations (VMs). CRISPR-Cas9 technology was used to generate a novel human iPSC line with an amino acid substitution L914F in the TIE2 receptor, known to cause VMs. This enabled us to study the differential effects of VM causative mutations in iECs in multiple in vitro models and assess their ability to form vessels in vivo. The analysis of TIE2 expression levels in TIE2 L914F iECs showed a significantly lower expression of TIE2 on mRNA and protein level, which has not been observed before due to a lack of models with endogenous edited TIE2 L914F and sparse patient data. Interestingly, the TIE2 pathway was still significantly upregulated and TIE2 showed high levels of phosphorylation. TIE2 L914F iECs exhibited dysregulated angiogenesis markers and upregulated migration capability, while proliferation was not affected. Under shear stress TIE2 L914F iECs showed reduced alignment in the flow direction and a larger cell area than TIE2 WT iECs. In summary, we developed a novel TIE2 L914F iPSC-derived iEC model and characterized it in multiple in vitro models. The model can be used in future work for drug screening for novel treatments for VMs., (© 2024. The Author(s).)

We show that a class of L-loop conformal ladder graphs are intimately related to twisted partition functions of free massive complex scalars in d=2L+1 dimensions. The graphs arise as four-point functions in certain two- and four-dimensional conformal fishnet models. The twisted thermal two-point function of the scalars becomes a generator of conformal ladder graphs for all loops. We argue that this correspondence is seeded by a system of two decoupled harmonic oscillators twisted by an imaginary chemical potential. We find a number of algebraic and differential relations among the conformal graphs that mirror the underlying free dynamics.

Metal ion-induced water pollution is attracting increasing public attention. Perovskite quantum dots and metal-organic frameworks (MOFs), owing to their outstanding properties, hold promise as ideal probes for detecting metal ions. In this study, a composite material, MAPbBr3@PCN-221(Fe), was prepared by encapsulating MAPbBr3 quantum dots with PCN-221(Fe), demonstrating high chemical stability and good reusability. The composite material shows a sensitive fluorescence turn-on signal in the presence of silver ions. The fluorescence intensity of the composite material exhibits a linear relationship with the concentration of Ag+ in the solution, with a low detection limit of 8.68 µM. Moreover, the fluorescence signal exhibits a strong selectivity for Ag+, enabling the detection of Ag+ concentration. This fluorescence turn-on signal originates from the Ag+-bridged energy transfer from the conductive band of MAPbBr3 to the excited state of the MOF, which is directly proportional to the concentration of silver ions. Simultaneously, this finding may open up a new possibility in artificial controlled energy transfer from perovskite to MOF for future development., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

A heterojunction of CdSe quantum dots in situ grown on the perovskite CsPb 2 Br 5 (CsPb 2 Br 5 /CdSe) for water-stable photoelectrochemical (PEC) sensing was simply synthesized using the hot-injection method. Due to the inherent built-in electric field and the matching band structure between CsPb 2 Br 5 and CdSe, the CsPb 2 Br 5 /CdSe p-n heterojunction demonstrates enhanced photoelectrochemical properties. Accelerated interfacial charge transfer and increased electron-hole pair separation enable hydrolysis-resistant CsPb 2 Br 5 /CdSe sensors to exhibit heightened sensitivity with an ultra-low detection limit (0.0124 μM) and a wide linear range (0.4-303.9 μM) in subsequent dopamine detection. Moreover, the CsPb 2 Br 5 /CdSe sensors show excellent anti-interference ability, as well as remarkable stability and reproducibility in water solvent. It is noteworthy that this work is conducted in an aqueous environment, which provides an inspiring and convenient way for photoelectric and photoelectrocatalysis applications based on water-resistant perovskites.

Myxobacteria have a complex life cycle and unique social behavior, and obtain nutrients by preying on bacteria and fungi in soil. Chitinase, β-1,3 glucanase and β-1,6 glucanase produced by myxobacteria can degrade the glycosidic bond of cell wall of some plant pathogenic fungi, resulting in a perforated structure in the cell wall. In addition, isooctanol produced by myxobacteria can lead to the accumulation of intracellular reactive oxygen species in some pathogenic fungi and induce cell apoptosis. Myxobacteria can also perforate the cell wall of some plant pathogenic oomycetes by β-1,3 glucanase, reduce the content of intracellular soluble protein and protective enzyme activity, affect the permeability of oomycete cell membrane, and aggravate the oxidative damage of pathogen cells. Small molecule compounds such as diisobutyl phthalate and myxovirescin produced by myxobacteria can inhibit the formation of biofilm and lipoprotein of bacteria, and cystobactamids can inhibit the activity of DNA gyrase, thus changing the permeability of bacterial cell membrane. Myxobacteria, as a new natural compound resource bank, can control plant pathogenic fungi, oomycetes and bacteria by producing carbohydrate active enzymes and small molecular compounds, so it has great potential in plant disease control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lele, Liangliang, Songyuan, Yang and Huirong.)

As an important and challenging problem in computer vision, scene graph generation (SGG) aims to find out the underlying semantic relationships among objects from a given image for scene understanding. Usually, prevalent SGG approaches adopt a learning pipeline with the assumption that there exists only a single relationship for a particular object pair. Considering the common phenomenon that a pair of objects can be attached by multiple relationships, we propose a multi-label scene graph generation pipeline with multi-grained features (MLMG-SGG), which formulates the relationship detection as a multi-label classification problem during training while generating multigraphs at inference time. In order to better model the fine-grained relationships, the proposed pipeline encodes the feature representation of SGG on different spatial scales by a specially designed Multi-Grained Module (MGM), resulting in the multi-grained (i.e., object-level and region-level) features of objects. Experimental results over the benchmark dataset demonstrate the significant performance gain of the proposed pipeline used as a plug-in for the state-of-the-art methods.

Traditional CNN-based pipelines for panoptic segmentation decompose the task into two subtasks, i.e., instance segmentation and semantic segmentation. In this way, they extract information with multiple branches, perform two subtasks separately and finally fuse the results. However, excessive feature extraction and complicated processes make them time-consuming. We propose IDNet to decompose panoptic segmentation at information level. IDNet only extracts two kinds of information and directly completes panoptic segmentation task, saving the efforts to extract extra information and to fuse subtasks. By decomposing panoptic segmentation into category information and location information and recomposing them with a serial pipeline, the process for panoptic segmentation is simplified greatly and unified with regard to stuff and things. We also adopt two correction losses specially designed for our serial pipeline, guaranteeing the overall predicting performance. As a result, IDNet strikes a better balance between effectiveness and efficiency, achieving the fastest inference speed of 24.2 FPS at a resolution of 800×1333 on a Tesla V100 GPU and a PQ of 43.8, which is comparable in one-stage CNN-based methods. The code will be released at https://github.com/AronLin/IDNet.

Si is a highly promising anode material due to its superior theoretical capacity of up to 3579 mAh/g. However, it is worth noting that Si anodes experience significant volume expansion (>300%) during charging and discharging. Due to the weak adhesion between the anode coating and the smooth Cu foil current collector, the volume-expanded Si anode easily peels off, thus damaging anode cycling performance. In the present study, a femtosecond laser with a wavelength of 515 nm is used to texture Cu foils with a hierarchical microstructure and nanostructure. The peeling and cracking phenomenon in the Si anode are successfully reduced, demonstrating that volume expansion is effectively mitigated, which is attributed to the high specific surface area of the nanostructure and the protection of the deep-ablated microgrooves. Moreover, the hierarchical structure reduces interfacial resistance to promote electron transfer. The Si anode achieves improved cycling stability and rate capability, and the influence of structural features on the aforementioned performance is studied. The Si anode on the 20 μm-thick Cu current collector with a groove density of 75% and a depth of 15 μm exhibits a capacity of 1182 mAh/g after 300 cycles at 1 C and shows a high-rate capacity of 684 mAh/g at 3 C.

Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing. The strategy increases sensitivity by one order of magnitude, identifying previously unknown SpCas9's off-target mutations in the humanized PCSK9 mouse model. To reduce off-target risks, we perform a bioinformatic search and identify a high-fidelity Cas9 variant of the II-B subfamily from Parasutterella secunda (PsCas9). PsCas9 shows improved specificity as compared to SpCas9 across multiple tested sites, both in vitro and in vivo, including the PCSK9 site. In the future, while PsCas9 will offer an alternative to SpCas9 for research and clinical use, the Duplex Sequencing workflow will enable a more sensitive assessment of Cas9 editing outcomes., (© 2023. Springer Nature Limited.)

Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing., (© 2023. Springer Nature Limited.)

Objective: We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology., Methods: Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining., Results: The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67., Conclusion: When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger., (© 2023 Wiley Periodicals LLC.)

Prime editing recently emerged as a next-generation approach for precise genome editing. Here we exploit DNA double-strand break (DSB) repair to develop two strategies that install precise genomic insertions using an SpCas9 nuclease-based prime editor (PEn). We first demonstrate that PEn coupled to a regular prime editing guide RNA (pegRNA) efficiently promotes short genomic insertions through a homology-dependent DSB repair mechanism. While PEn editing leads to increased levels of by-products, it can rescue pegRNAs that perform poorly with a nickase-based prime editor. We also present a small molecule approach that yields increased product purity of PEn editing. Next, we develop a homology-independent PEn editing strategy, which installs genomic insertions at DSBs through the non-homologous end joining pathway (NHEJ). Lastly, we show that PEn-mediated insertions at DSBs prevent Cas9-induced large chromosomal deletions and provide evidence that continuous Cas9-mediated cutting is one of the mechanisms by which Cas9-induced large deletions arise. Altogether, this work expands the current prime editing toolbox by leveraging distinct DNA repair mechanisms including NHEJ, which represents the primary pathway of DSB repair in mammalian cells., (© 2022. The Author(s).)

Dynamic routing networks, aimed at finding the best routing paths in the networks, have achieved significant improvements to neural networks in terms of accuracy and efficiency. In this paper, we see dynamic routing networks in a fresh light, formulating a routing method as a mapping from a sample space to a routing space. From the perspective of space mapping, prevalent methods of dynamic routing did not take into account how inference paths would be distributed in the routing space. Thus, we propose a novel method, termed CoDiNet, to model the relationship between a sample space and a routing space by regularizing the distribution of routing paths with the properties of consistency and diversity. Specifically, samples with similar semantics should be mapped into the same area in routing space, while those with dissimilar semantics should be mapped into different areas. Moreover, we design a customizable dynamic routing module, which can strike a balance between accuracy and efficiency. When deployed upon ResNet models, our method achieves higher performance and effectively reduces average computational cost on four widely used datasets.

Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems.

Objective: Epidural fluid collection (EFC) is one of the postoperative complications of cranioplasty and is easily ignored. Not only the predictive factors of EFC formation are unknown, the pathologic mechanisms are also unknown. We determined to analyze the predictive factors and the mechanism of EFC formation., Methods: A total of 340 patients underwent cranioplasty were retrospectively analyzed in this study. A series of factors were compared in the EFC and none-EFC groups and farther compared in the progress epidural fluid collection (PEFC) and none-PEFC subgroups to determine the predictive factors. The t test, χ test, and logistic regression analysis were used in statistical analysis., Results: The rate of EFC formation was 34.41%, and the size of skull defect, preoperative volume of collapse, intraoperative dura suspending, a pre- or intraoperative ventriculoperitoneal shunt (V-P shunt), and an postoperative air bubble in epidural space were predictive factors for EFC formation. Furthermore, the incidence of PEFC was 10.29%, the size of skull defects and intraoperative dura suspending were predictive factors for PEFC formation. The protein ratio and lactate dehydrogenase (LDH) ratio of effusion to serum were >0.5 and 0.6, respectively. There was no adverse prognosis., Conclusions: Although EFC can be treated with conservative therapy, we need to emphasize EFC incidence and development. As neurosurgeons, it is necessary to analyze the preoperative predictive factors of EFC, pay attention to the intraoperative details such as dura suspending to prevent PEFC formation, and the early intervention should be performed in the postoperative.

Chinese hamster ovary (CHO) cells are the preferred workhorse for the biopharmaceutical industry, and CRISPR/Cas9 has proven powerful for generating targeted gene perturbations in CHO cells. Here, we expand the CRISPR engineering toolbox with CRISPR activation (CRISPRa) to increase transcription of endogenous genes. We successfully increased transcription of Mgat3 and St6gal1, and verified their activity on a functional level by subsequently detecting that the appropriate glycan structures were produced. This study demonstrates that CRISPRa can make targeted alterations of CHO cells for desired phenotypes., (© 2019 Wiley Periodicals, Inc.)

Production of proteins and biochemicals in microbial cell factories is often limited by carbon and energy spent on excess biomass formation. To address this issue, we developed several genetic growth switches based on CRISPR interference technology. We demonstrate that growth of Escherichia coli can be controlled by repressing the DNA replication machinery, by targeting dnaA and oriC, or by blocking nucleotide synthesis through pyrF or thyA. This way, total GFP-protein production could be increased by up to 2.2-fold. Single-cell dynamic tracking in microfluidic systems was used to confirm functionality of the growth switches. Decoupling of growth from production of biochemicals was demonstrated for mevalonate, a precursor for isoprenoid compounds. Mass yield of mevalonate was increased by 41%, and production was maintained for more than 45h after activation of the pyrF-based growth switch. The developed methods represent a promising approach for increasing production yield and titer for proteins and biochemicals., (Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)