Extension and parameterization of high-order density dependence in Skyrme forces

The three-body force is indispensable in nuclear energy density functionals which leads to a density dependent two-body term in the Hartree-Fock approach. Usually a single factional power of density dependency has been adopted. We consider the possibility of an additional higher-order density dependence in extended Skyrme forces. As a result, new extended Skyrme parametertizations based on the SLy4 force are obtained and the improvements in descriptions of global nuclei have been demonstrated. The higher-order term can also substantially affect nuclear properties in the high density region in general ways.Comment: 6 pages, 5 figure

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

From colonial port to socialist metropolis: imperialist legacies and the making of ‘New Dalian’

This article explores the transformation of the city of Dalian from a colonial export port to an industrialized core city of the Japanese wartime empire and finally a model production city of the People's Republic of China. These shifts in the economic and political function of the city also resulted in complex identity issues for Dalian's urban residents. Dalian's rise reminds that there were trajectories of urban development and modernity in China which were different from that of Shanghai. Dalian provides an important, local view of the transition from empire to nation in this strategically important part of Manchuria

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Identification of Cement Pavement with Temperature Effect and Evaluation of Polymer Grouting Effect

The falling weight deflectometer (FWD) detection system benefits from its outstanding characteristics of no damage, fast speed, and high precision. The warping deformation of cement concrete pavement occurs due to the temperature difference along the depth of the slab, which makes FWD detect different results under different temperature fields. In this study, we systematically carried out the cement pavement’s temperature field and deflection test. The experimental data were analyzed to obtain the temperature variation law of the top and bottom of the pavement slab every day. By establishing a three-dimensional finite element model of cement pavement with a multi-layer elastic foundation type, the influence of the temperature difference at the bottom of the slab on the deflection of the center point of the slab corner load under different working conditions, different seasons, different loads and whether there is polymer filling in the void area was studied. We summarize the correlation between the temperature difference and the influence coefficient and propose the cement pavement void identification and polymer grouting effect evaluation method considering the temperature effect

Twelve years' observation of multiple familial trichoepithelioma with squamous carcinoma

Long-standing trichoepithelioma lesion on scalp with 12 years follow-up. The patient was observed for 12 years, and the carcinoma recurred 3 times during 8 years after surgical excision and radiation therapy. Malignant transformation may occur in multiple familial trichoepitheliomas; Moderate radiation therapy should be given for malignant transformation patients with lower radiation dose and shorter time. Removing the trichoepithelioma as soon as possible if the tumor suddenly or continuously increased is recommended

Robust Shadow Estimation

Efficiently estimating properties of large and strongly coupled quantum systems is a central focus in many-body physics and quantum information theory. While quantum computers promise speedups for many of these tasks, near-term devices are prone to noise that will generally reduce the accuracy of such estimates. Here, we propose a sample-efficient and noise-resilient protocol for learning properties of quantum states building on the shadow estimation scheme [Huang et al., Nature Physics 16, 1050-1057 (2020)]. By introducing an experimentally friendly calibration procedure, our protocol can efficiently characterize and mitigate noises in the shadow estimation scheme, given only minimal assumptions on the experimental conditions. When the strength of noises can be bounded, our protocol approximately retains the same order of sample efficiency as the standard shadow estimation scheme, while also possessing a provable noise resilience. We give rigorous bounds on the sample complexity of our protocol and demonstrate its performance with several numerical experiments, including estimations of quantum fidelity, correlation functions and energy expectations, etc., which highlight a wide spectrum of potential applications of our protocol on near-term devices