Concept for a Future Super Proton-Proton Collider

Following the discovery of the Higgs boson at LHC, new large colliders are being studied by the international high-energy community to explore Higgs physics in detail and new physics beyond the Standard Model. In China, a two-stage circular collider project CEPC-SPPC is proposed, with the first stage CEPC (Circular Electron Positron Collier, a so-called Higgs factory) focused on Higgs physics, and the second stage SPPC (Super Proton-Proton Collider) focused on new physics beyond the Standard Model. This paper discusses this second stage.Comment: 34 pages, 8 figures, 5 table

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Impaired membrane targeting and aberrant cellular localization of human Cx26 mutants associated with inherited recessive hearing loss

Abstract Conclusion: This study demonstrated that five Cx26 mutations (R32H, S199F, 572delT, 631-632delGT, and Y155X) affect gap junction (GJ) functions by causing impaired membrane targeting and aberrant cellular localization, and one mutation (R165W) leads to a constriction of the channel pore with no dye coupling. Objective: To investigate the pathogenetic roles of six recessive Cx26 mutations (p.R32H, p.R165W, p.S199F, c.572delT, c.631-632delGT, and p.Y155X), which have not been functionally analyzed in vitro. Methods: The six mutants and wild-type Cx26 (wtCx26) were cloned into the EcoRI and SalI sites of pEGFP-N1 vector. We transfected the seven constructs into HeLa cells, followed by analysis of their protein expression using the western blot method, study of the protein localizations and gap junction-plaques on the cytomembrane under confocal microscopy, and assessment of the dye coupling of the mutated GJ channels by intercellular dye transfer experiment. Results: p.R165W targeted the cytomembrane and formed GJ-like structures in adjacent HeLa cells, causing null dye coupling. The mutants (p.R32H, p.S199F, c.572delT, c.631-632delGT, and p.Y155X) failed to reach the cell surface, and perfectly co-localized with endoplasmic reticulum (ER) throughout the cells

Preservation of superior laryngeal nerve in transoral surgery: A technology to enhance the recovery of swallowing function after surgery of hypopharyngeal carcinoma

Objectives: We intended to preserve the internal branch of superior laryngeal nerve in transoral surgery of hypopharyngeal squamous cell carcinoma and observe swallowing function recovery. Methods: 26 patients with hypopharyngeal squamous cell carcinoma underwent transoral surgery with the preservation of internal branch of superior laryngeal nerve. Sensation in the pharyngolaryngeal mucosa was tested by flexible laryngoscope and swallow function was evaluated by water swallow test and MD Anderson Dysphagia Inventory questionnaire after surgery. Results: Surgeries were successfully performed in all patients. The internal branch of superior laryngeal nerve were preserved in all patients. Testing of mucosa sensation revealed the presence of the cough reflex in most patients. The water swallow test showed that 12 cases (46.15%) on the 1st day, 23 cases (88.46%) on the 7th day and 25 cases (96.15%) on the 14th day after operation had normal swallowing function. The mean score of MD Anderson Dysphagia Inventory was 98 on the 14th day after operation. All patients achieved an oral soft diet at a median of 3 days (range, 2–6 days), full normal oral diet at a median of 5.5 days (range, 4–10 days) and removal of the nasogastric tube at a median of 6 days (range, 5–11 days). During the two-year follow-up, 3 patients recured, 1 patient died of lung metastasis. Conclusions: Preserving of the internal branch of superior laryngeal nerve in transoral surgery is feasible, and it can help to achieve a satisfactory recovery of the swallowing function after surgery of hypopharyngeal squamous cell carcinoma

Facile Synthesis of Enzyme-Inorganic Hybrid Nanoflowers and Its Application as a Colorimetric Platform for Visual Detection of Hydrogen Peroxide and Phenol

This study reports a facile approach for the synthesis of horseradish peroxidise (HRP)-inorganic hybrid nanoflowers by self-assembly of HRP and copper phosphate (Cu₃(PO₄)₂·3H₂O) in aqueous solution. Several reaction parameters that affect the formation of the hybrid nanoflowers were investigated and a hierarchical flowerlike spherical structure with hundreds of nanopetals was obtained under the optimum synthetic conditions. The enzymatic activity of HRP embedded in hybrid naonflowers was evaluated based on the principle of HRP catalyzing the oxidation of <i>o</i>-phenylenediamine (OPD) in the presence of hydrogen peroxide (H₂O₂). The results showed that 506% enhancement of enzymatic activity in the hybrid nanoflowers could be achieved compared with the free HRP in solution. Taking advantages of the structural feature with catalytic property, a nanoflower-based colorimetric platform was newly designed and applied for fast and sensitive visual detection of H₂O₂ and phenol. The limits of detection (LODs) for H₂O₂ and phenol were as low as 0.5 μM and 1.0 μM by the naked-eye visualization, which meet the requirements of detection of both analytes in clinical diagnosis and environmental water. The proposed method has been successfully applied to the analysis of low-level H₂O₂ in spiked human serum and phenol in sewage, respectively. The recoveries for all the determinations were higher than 92.6%. In addition, the hybrid nanoflowers exhibited excellent reusability and reproducibility in cycle analysis. These primary results demonstrate that the hybrid nanoflowers have a great potential for applications in biomedical and environmental chemistry

The Role of EGFR/PI3K/Akt/cyclinD1 Signaling Pathway in Acquired Middle Ear Cholesteatoma

Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore, in vitro studies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma