The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project.Comment: This document is a collaborative effort, 185 pages, 110 figure

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This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Serum Dickkopf-1 expression level positively correlates with a poor prognosis in breast cancer Diagnostic Pathology 2014, 9:161 doi:10.1186/s13000-014-0161-

Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway

Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients

Abstract Background Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. Methods We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression. Results Multivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p < 0.05] and dMMR status was the only risk factor for low MHC class I expression (OR = 15.34; p < 0.001). Conclusions High CD8 and low MHC class I expression suggests the contradiction and complexity of immune microenvironment in dMMR CRC patients. Some other immunocytes such as CD56+ cells might also participate in the process of immune checkpoint inhibition, whereas needs further investigations

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s