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A superconducting radio-frequency (SRF) photo injector is in operation at the electron linac for beams with high brilliance and low emittance (ELBE) radiation center and generates continuous wave (CW) electron beams with high average current and high brightness for user operation since 2018. The speed of emittance measurement at the SRF gun beamline can be increased by improving the slit-scan system, thus the measurement time for one phase space mapping can be shortened from about 15 minutes to 90 seconds. A parallel algorithm and machine learning have been used to reduce the beamlet image noise. In order to estimate the uncertainty in the calculation of normalized emittance, we analyze the main error contributions such as slit position uncertainty, image noise, space charge effects and energy measurement inaccuracy.

The European physical journal / Plus 138(2), 158 (2023). doi:10.1140/epjp/s13360-023-03720-z special issue: "Focus Point on Accelerator-based Photon Science Strategy, Prospects and Roadmap in Europe: a Forward View to 2030 / guest editors: R. Abela, T. Tschentscher, J. Susini, G. García", Published by Springer, Berlin ; Heidelberg

Introduction: Animal models of human diseases are used extensively to interrogate molecular mechanisms in a reductionist fashion. We tested whether aggregation and integration of preclinical data can identify new causative pathways that faithfully model human disease mechanisms. We have termed this novel technique, the Preclinical Science Integration and Translation (PRESCIANT) method. Methods and Results: Data were extracted from 716 manuscripts in the journal Arteriosclerosis, Thrombosis, and Vascular Biology from 1995-2019 using the apolipoprotein E knockout mouse (ApoE-KO) to study atherosclerosis. We identified 360 unique studies in which genes were experimentally perturbed in ApoE-KO mice to impact atherosclerotic plaque size and/or composition. Impacts of the interventions on plaque size, inflammation, and lipid content were analyzed using Ingenuity Pathway Analysis. The top upstream regulatory network (sc-58125, a COX2 inhibitor) linked 37.2% (134) of the genes implicated in atherosclerosis into a single network. Further, Ingenuity Pathway Analysis identified TREM1 signaling, LXR/RXR activation, and renin-angiotensin signaling as the top 3 pathways associated with changes in atherosclerosis parameters. Specifically, early atherogenesis genes were enriched with pathways associated with inflammatory cell migration and infiltration (including TREM1) whereas late atherosclerosis genes were associated with cell metabolism and survival (including LXR/RXR activation). These two pathways were interrogated in a clinical cohort of 88,660 patients by testing for association between genetically predicted expression of the human homologs of mouse pathway genes and a composite phenotype composed of 27 human atherosclerosis diagnoses. There was a significant enrichment (p Conclusion: PRESCIANT can successfully leverage decades of animal investigations to translate results from large-volume singular preclinical studies to make novel causal inferences into human disease.

Objective:Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease.Approach and Results:Of 716 articles published inATVBfrom 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. TREM1 (triggering receptor expressed on myeloid cells) signaling and LXR/RXR (liver X receptor/retinoid X receptor) activation were identified as the top atherosclerosis-associated pathways in mice (bothP−4, TREM1 implicated early and LXR/RXR in late atherogenesis). The top upstream regulatory network in mice (sc-58125, a COX2 inhibitor) linked 64.0% of the genes into a single network. The pathways and networks identified in mice were interrogated by testing for associations between the genetically predicted gene expression of each mouse pathway-identified human homolog with clinical atherosclerosis in a cohort of 88 660 human subjects. Homologous human pathways and networks were significantly enriched for gene-atherosclerosis associations (empiricalPPTGS2) with increased likelihood of atherosclerosis (odds ratio, 1.68 per SD of genetically predicted gene expression;P=1.07×10−6).Conclusions:PRESCIANT (Preclinical Science Integration and Translation) leverages published preclinical investigations to identify high-confidence pathways, networks, and regulators of human disease.

Rabies virus is an enveloped negative-stranded RNA virus belonging to the family Rhabdoviridae. It can be successfully controlled by vaccination however, there are still tens of thousands of deaths each year caused by rabies virus due to its mutations and complexity. A better understanding of the interaction between the rabies virus and the host might help solve this problem. Therefore, in this study, we used two-dimensional electrophoresis to investigate the protein expression of rabies virus-infected mice. This can help us to understand the impact of rabies virus on host protein expression during infection. For our experiment, two-dimensional electrophoresis was used to analyze the differential proteomics of the brain of 10- and 20-day-old suckling mice infected with attenuated rabies virus strain SRV9. The results showed that the expression levels of 10 protein spots had been up- or down-regulated at least 2-fold. Using MALDI-TOF-MS, we identified 8 differentially expressed proteins. We have identified proteins, namely hnRNP L, DPYSL3, NECAPs, and transaldolase that might be closely related to the susceptibility of SRV9 in suckling mice. Keywords: rabies virus; attenuated strain; suckling mouse; two-dimensional electrophoresis; proteomics.

© 2020, The Author(s). Background: Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterized by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results: MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE NuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE of MtMP genes was observed in < 50% of tissues and notably MtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion of NuMP (up to 60%) and MtMP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of NuMP, 77% of MtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all MtMP genes in the direction of dominant NuMP genes expression. The NuMP and MtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathway. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions: The results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.

The nematode Caenorhabditis elegans is a suitable model organism in drug screening. Traditionally worms are grown on agar plates, posing many challenges for long-term culture and phenotyping of animals under identical conditions. Microfluidics allows for ‘personalized’ phenotyping, as microfluidic chips permit collecting individual responses over worms’ full life. Here, we present a multiplexed, high-throughput, high-resolution microfluidic approach to culture C. elegans from embryo to the adult stage at single animal resolution. We allocated single embryos to growth chambers, for observing the main embryonic and post-embryonic development stages and phenotypes, while exposing worms to up to 8 different well-controlled chemical conditions. Our approach allowed eliminating bacteria aggregation and biofilm formation-related clogging issues, which enabled us performing up to 80 hours of automated single worm culture studies. Our microfluidic platform is linked with an automated phenotyping code that registers organism-associated phenotypes at high-throughput. We validated our platform with a dose-response study of the anthelmintic drug tetramisole by studying its influence through the life cycle of the nematodes. In parallel, we could observe development effects and variations in single embryo and worm viability due to the bleaching procedure that is standardly used for harvesting the embryos from a worm culture agar plate.

Lacking labeled examples of working numerical strategies, adapting an iterative solver to accommodate a numerical issue, e.g., density discontinuities in the pressure Poisson equation, is non-trivial and usually involves a lot of trial and error. Here, we resort to evolutionary neural network. A evolutionary neural network observes the outcome of an action and adapts its strategy accordingly. The process requires no labeled data but only a measure of a network’s performance at a task. Applying neuro-evolution and adapting the Jacobi iterative method for the pressure Poisson equation with density discontinuities, we show that the adapted Jacobi method is able to accommodate density discontinuities.

Continental breakup represents the successful process of rifting and thinning of the continental lithosphere, leading to plate rupture and initiation of oceanic crust formation. Magmatism during breakup seems to follow a path of either excessive, transient magmatism (magma-rich margins) or of igneous starvation (magma-poor margins). The latter type is characterized by extreme continental lithospheric extension and mantle exhumation prior to igneous oceanic crust formation. Discovery of magma-poor margins has raised fundamental questions about the onset of ocean-floor type magmatism, and has guided interpretation of seismic data across many rifted margins, including the highly extended northern South China Sea margin. Here we report International Ocean Discovery Program drilling data from the northern South China Sea margin, testing the magma-poor margin model outside the North Atlantic. Contrary to expectations, results show initiation of Mid-Ocean Ridge basalt type magmatism during breakup, with a narrow and rapid transition into igneous oceanic crust. Coring and seismic data suggest that fast lithospheric extension without mantle exhumation generated a margin structure between the two endmembers. Asthenospheric upwelling yielding Mid-Ocean Ridge basalt-type magmatism from normal-temperature mantle during final breakup is interpreted to reflect rapid rifting within thin pre-rift lithosphere.

Our experiment focused on investigating the P content dependences of the ability to form glass, the soft-magnetic properties of, and the clusters in melting Fe85−xSi4B11Px (x = 1–6), amorphous soft-magnetic alloys. The experimental results demonstrate that the alloys with proper P content (3–6 at.%) are prone to form a completely amorphous structure with a larger glass-forming ability (GFA); hence, amorphous alloys prepared by industry-grade raw materials can be well produced in an air atmosphere. The melted alloy has higher stability and larger GFA when there is no dominant cluster or when multi-species clusters coexist. The Fe82Si4B11P3 amorphous alloy exhibited a high saturation magnetic flux density of up to 1.66 T, a low coercivity of about 2.2 A/m, and a high effective permeability of more than 1.2 × 104 at 1 kHz under a field of 1 A/m. The combination of excellent soft-magnetic properties, good productivity and low cost stability suggest that the FeSiBP alloys are promising soft-magnetic materials, particularly with applications in the electronic industry.

In this paper, the alloying effects of minor Cu on the relationship between microstructure and corrosion resistance of (Fe0·76Si0·09B0·1P0·05)99 − xNb1Cux (x = 0, 0·25, 0·5, 0·75, 1) ferromagnetic bulk metallic glasses (BMGs) were investigated in details. The microstructure characterisation has revealed that the introduction of proper Cu elements leads to the presence of α-Fe clusters in the as-cast amorphous rods. In addition, α-Fe nanocrystals with a suitable size and volume fraction can accelerate the formation of the protective passive layers at nanocrystals/amorphous interfaces, and lead to the improvement of corrosion resistance. However, when the Cu content x exceeds 0·75, the corrosion resistance of the FeSiBPNbCu BMGs reduces significantly. All the results imply that the Cu content plays a key role in the characteristic size of α-Fe nanoparticles embedded in the glassy matrix, and there is a dependent correlation between the corrosion resistance and the microstructure.

The effects of Nb addition on the microstructure, crystallisation behavior, and soft magnetic properties of Fe83.25−xP9C7Cu0.75Nbx (x = 0, 0.5, 1, 2, 3) alloys were investigated. The experimental results demonstrate that proper Nb addition improves the glass-forming ability and enhances the soft magnetic properties of this alloy system. The Fe82.75P9C7Cu0.75Nb0.5 alloy annealed at 573–773 K for 10 min, in which α-Fe nanocrystalline phase with diameter of 5–20 nm precipitated from the amorphous matrix, while alloy annealed at 743 K shows the best soft magnetic properties. The resulting Fe82.75P9C7Cu0.75Nb0.5 nanocrystalline alloy exhibited a high saturation magnetic flux density, B s , of 1.66 T; a low coercivity, H c , of 6.8 A/m; and a high effective permeability, μ e , of 29,000 at 1 kHz. These characteristics are superior to corresponding properties of FePC alloys. These results indicate that this alloy is a promising soft magnetic material.

In this paper, we describe the effects of substituting Co for Fe on the microstructure, crystallisation behaviour, and soft magnetic properties of (Fe1−x Co x )84Si4B8P3Cu1 (x = 0.35, 0.5, 0.65) alloys. The results demonstrate that as the Co content in the alloy increases, the heat treatment temperature also improves. When x = 0.35 Co was substituted for Fe in Fe84Si4B8P3Cu1 alloy, there was a significant enhancement in the interval temperature (ΔT x ) between the two crystallization temperatures, and this resulted in the largest crystalline volume fraction (V cry ). When annealing at 625–800 K, we observed a dual-phase nanocrystalline structure in all the specimens, which was composed of nanocrystals with average grain size of about 9–28 nm embedded in the residual amorphous matrix. The (Fe0.65Co0.35)84Si4B8P3Cu1 nanocrystalline alloy exhibited a high saturation magnetic flux density, B s , of 1.68 T; a low coercivity, H c , of 5.4 A/m; and a high effective permeability, µ e , of 29,600 at 1 kHz. Hence, these results indicate that this alloy is promising for use as a soft magnetic material.

The effects of the addition of Cu on the crystallisation behaviour, soft magnetic properties, and corrosion behaviour of Fe84-xP9C7Cux (x = 0–1.15) alloys were investigated. The experimental results demonstrate that the glass-forming ability of this alloy was improved and the soft magnetic properties of the alloy system were enhanced by proper Cu addition. FePCCu nanocrystalline alloys with a dispersed α-Fe phase were obtained by appropriately annealing the melt-spun ribbons at 693 K for 2 min. The Fe83.25P9C7Cu0.75 nanocrystalline alloy exhibited a high saturation magnetic flux density, B s , of 1.64 T; a low coercivity, H c , of 3.9 A/m; and a high effective permeability, μ e , of 21,000 at 1 kHz. These characteristics are superior to corresponding properties of FePC alloys. Furthermore, the corrosion resistance of this nanocrystalline alloy increases when elevating the annealing temperature and was confirmed to be improved with respect to the corresponding amorphous alloy. These results indicate that this alloy is a promising soft magnetic material.

Observational study is a method most commonly used in the etiology study of epidemiology, but confounders, always distort the true causality between exposure and outcome when local inferencing. In order to eliminate these confounding, the determining of variables which need to be adjusted become a key issue. Directed acyclic graph(DAG)could visualize complex causality, provide a simple and intuitive way to identify the confounding, and convert it into the finding of the minimal sufficient adjustment for the control of confounding. On the one hand, directed acyclic graph can choose less variables, which increase statistical efficiency of the analysis. On the other hand, it could help avoiding variables that is not measured or with missing values. In a word, the directed acyclic graph could facilitate the reveal of the real causality effectively.

To analyze the characteristics and factors affecting the recurrence in esophageal cancer within the first year after esophagectomy.We reviewed retrospectively the clinical and follow-up data of 320 patients who underwent surgical treatment from April 2009 to April 2013 in Sichuan Provincial Cancer Hospital.72 cases (72/320, 22.5%) had tumor recurrence within the first year after surgery. The average recurrence time was 6.89±3.53 months and the median recurrence time was 6.02 months. Univariate analysis showed that T stage, N stage, G grade, and pathological stage are related to the recurrence (P0.05 for all). Logistic regression analysis showed that pathological stage is an independent risk factor for recurrence (P=0.002). There were 46 cases (46/72, 63.9%) of local recurrence and 26 cases (26/72, 36.1%) of distant metastasis. Among the 46 cases of local recurrence, 27 cases (27/46, 58.7%) had upper mediastinal lymph node metastasis. Among the 26 cases of distant metastasis, there were 11 cases (11/26, 42.3%) of pulmonary metastasis. Among the 72 cases of recurrence, the average number of dissected lymph nodes and involved nodes were 29.40±11.41 and 4.37±5.65, respectively, in patients with distant metastasis, and 21.18±10.37 and 1.91±2.14, respectively, in patients with local recurrence. Both the number of dissected and involved lymph nodes were significantly higher in the patients with distant metastasis (P0.05).Lymph node metastasis is the most common pattern of recent relapse after esophagectomy, and pathological stage is an independent risk factor for recurrence within the first year after surgery. Standardized lymph node dissection and rational treatment strategy is the key measures to reduce early recurrence of esophageal cancer.