77 research outputs found

    Intracerebral metaplastic meningioma with prominent ossification and extensive calcification

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    We present a patient (male 26 years) with a short history of recurrent seizures induced by a largely intracerebrally located frontal lobe meningioma. The tumor displayed a heretofore unpublished combination of extensive metaplastic bone formation and prominent non-psammomatous calcifications with focal chicken-wire pattern

    Glutathione S-Transferase Pi expression in invasive ductal breast carcinoma

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    Ph.DDOCTOR OF MEDICIN

    Insulin Stimulates Adipogenesis through the Akt-TSC2-mTORC1 Pathway

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    BACKGROUND:The signaling pathways imposing hormonal control over adipocyte differentiation are poorly understood. While insulin and Akt signaling have been found previously to be essential for adipogenesis, the relative importance of their many downstream branches have not been defined. One direct substrate that is inhibited by Akt-mediated phosphorylation is the tuberous sclerosis complex 2 (TSC2) protein, which associates with TSC1 and acts as a critical negative regulator of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). Loss of function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1-dependent feedback mechanisms and loss of mTORC2 activity, leads to a concomitant block of Akt signaling to its other downstream targets. METHODOLOGY/PRINCIPAL FINDINGS:We find that, despite severe insulin resistance and the absence of Akt signaling, TSC2-deficient mouse embryo fibroblasts and 3T3-L1 pre-adipocytes display enhanced adipocyte differentiation that is dependent on the elevated mTORC1 activity in these cells. Activation of mTORC1 causes a robust increase in the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master transcriptional regulator of adipocyte differentiation. In examining the requirements for different Akt-mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin-stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis. Finally, renal angiomyolipomas from patients with tuberous sclerosis complex contain both adipose and smooth muscle-like components with activated mTORC1 signaling and elevated PPARgamma expression. CONCLUSIONS/SIGNIFICANCE:This study demonstrates that activation of mTORC1 signaling is a critical step in adipocyte differentiation and identifies TSC2 as a primary target of Akt driving this process. Therefore, the TSC1-TSC2 complex regulates the differentiation of mesenchymal cell lineages, at least in part, through its control of mTORC1 activity and PPARgamma expression

    A (Bi<sub>2</sub>O<sub>2</sub>)<sup>2+</sup> layer as a significant carrier generator and transmission channel in CaBi<sub>2</sub>Nb<sub>2</sub>O<sub>9</sub> platelets for enhanced piezo-photo-catalytic performance

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    The low photocatalytic conversion efficiency, poor light absorption and high charge recombination rate of traditional semiconductor photocatalysts continues to be a significant research challenge. In this paper, by combining detailed experimental and modeling techniques, we report on the unique potential of CaBi2Nb2O9 (CBN) platelets that can couple both piezo- and photo- multi-field effects to overcome these issues and realize high-efficiency hydrogen production and dye degradation. The surface adsorption of OH− and dye molecules is improved as a result of the built-in electric field, thereby demonstrating an enhanced piezo- and photo-catalytic H2 production activity, with a high rate of 96.83 μmol g−1 h−1. The piezo-photocatalytic decomposition ratio for 100 mL RhB dye of 10 mg/L can reach up to 98.7 % in 32 min using only 0.05 mg of CBN platelets (k = 0.131 min−1). It is shown that the careful introduction of regularly arranged layers of (Bi2O2)2+ into the CBN platelet structure provides a high transport of photoelectrons via a pathway of (Bi2O2)2+ → (CaNb2O7)2− → CBN surface. The electron density distribution of Bi atoms is also found to be enriched on the facets of (020) and (200) crystal planes in the CBN platelets, which is beneficial to the oxidation reduction reaction. Furthermore, the large deformation of CBN platelet during the application of ultrasound leads to an increase of the piezo-induced built-in electric field to improve charge separation and migration. This work therefore provides a new perspective in the design and manufacture of advanced materials with enhanced piezo- and photo-catalytic performance by exploiting multi-field coupling effects.</p

    A (Bi<sub>2</sub>O<sub>2</sub>)<sup>2+</sup> layer as a significant carrier generator and transmission channel in CaBi<sub>2</sub>Nb<sub>2</sub>O<sub>9</sub> platelets for enhanced piezo-photo-catalytic performance

    Get PDF
    The low photocatalytic conversion efficiency, poor light absorption and high charge recombination rate of traditional semiconductor photocatalysts continues to be a significant research challenge. In this paper, by combining detailed experimental and modeling techniques, we report on the unique potential of CaBi2Nb2O9 (CBN) platelets that can couple both piezo- and photo- multi-field effects to overcome these issues and realize high-efficiency hydrogen production and dye degradation. The surface adsorption of OH− and dye molecules is improved as a result of the built-in electric field, thereby demonstrating an enhanced piezo- and photo-catalytic H2 production activity, with a high rate of 96.83 μmol g−1 h−1. The piezo-photocatalytic decomposition ratio for 100 mL RhB dye of 10 mg/L can reach up to 98.7 % in 32 min using only 0.05 mg of CBN platelets (k = 0.131 min−1). It is shown that the careful introduction of regularly arranged layers of (Bi2O2)2+ into the CBN platelet structure provides a high transport of photoelectrons via a pathway of (Bi2O2)2+ → (CaNb2O7)2− → CBN surface. The electron density distribution of Bi atoms is also found to be enriched on the facets of (020) and (200) crystal planes in the CBN platelets, which is beneficial to the oxidation reduction reaction. Furthermore, the large deformation of CBN platelet during the application of ultrasound leads to an increase of the piezo-induced built-in electric field to improve charge separation and migration. This work therefore provides a new perspective in the design and manufacture of advanced materials with enhanced piezo- and photo-catalytic performance by exploiting multi-field coupling effects.</p

    A new method of predicting the energy consumption of additive manufacturing considering the component working state

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    With the increase in environmental awareness, coupled with an emphasis on environmental policy, achieving sustainable manufacturing is increasingly important. Additive manufacturing (AM) is an attractive technology for achieving sustainable manufacturing. However, with the diversity of AM types and various working states of machines’ components, a general method to forecast the energy consumption of AM is lacking. This paper proposes a new model considering the power of each component, the time of each process and the working state of each component to predict the energy consumption. Fused deposition modeling, which is a typical AM process, was selected to demonstrate the effectiveness of the proposed model. It was found that the proposed model had a higher prediction accuracy compared to the specific energy model and the process-based energy consumption model. The proposed model could be easily integrated into the software to visualize the printing time and energy consumption of each process in each component, and, further, provide a reference for coordinating the optimization of parts’ quality and energy consumptio

    Somatic mutations in facial skin from countries of contrasting skin cancer risk

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    The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes

    DeepSeek LLM: Scaling Open-Source Language Models with Longtermism

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    The rapid development of open-source large language models (LLMs) has been truly remarkable. However, the scaling law described in previous literature presents varying conclusions, which casts a dark cloud over scaling LLMs. We delve into the study of scaling laws and present our distinctive findings that facilitate scaling of large scale models in two commonly used open-source configurations, 7B and 67B. Guided by the scaling laws, we introduce DeepSeek LLM, a project dedicated to advancing open-source language models with a long-term perspective. To support the pre-training phase, we have developed a dataset that currently consists of 2 trillion tokens and is continuously expanding. We further conduct supervised fine-tuning (SFT) and Direct Preference Optimization (DPO) on DeepSeek LLM Base models, resulting in the creation of DeepSeek Chat models. Our evaluation results demonstrate that DeepSeek LLM 67B surpasses LLaMA-2 70B on various benchmarks, particularly in the domains of code, mathematics, and reasoning. Furthermore, open-ended evaluations reveal that DeepSeek LLM 67B Chat exhibits superior performance compared to GPT-3.5

    A heterozygous moth genome provides insights into herbivory and detoxification

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    How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al
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