Generation of GHZ-type and \emph{W}-type entangled coherent states of three-cavity fields

We present experimental schemes to prepare the three-cavity GHZ-type and \emph{W}-type entangled coherent states in the context of dispersive cavity quantum electrodynamics. The schemes can be easily generalized to prepare the GHZ-type and \emph{W}-type entangled coherent states of $n$-cavity fields. The discussion of our schemes indicates that it can be realized by current technologies.Comment: 4 pages, 2 figure

Pretreatment carcinoembryonic antigen level is a risk factor for para-aortic lymph node recurrence in addition to squamous cell carcinoma antigen following definitive concurrent chemoradiotherapy for squamous cell carcinoma of the uterine cervix

<p>Abstract</p> <p>Background</p> <p>To identify pretreatment carcinoembryonic antigen (CEA) levels as a risk factor for para-aortic lymph node (PALN) recurrence following concurrent chemoradiotherapy (CCRT) for cervical cancer.</p> <p>Methods</p> <p>From March 1995 to January 2008, 188 patients with squamous cell carcinoma (SCC) of the uterine cervix were analyzed retrospectively. No patient received PALN irradiation as the initial treatment. CEA and squamous cell carcinoma antigen (SCC-Ag) were measured before and after radiotherapy. PALN recurrence was detected by computer tomography (CT) scans. We analyzed the actuarial rates of PALN recurrence by using Kaplan-Meier curves. Multivariate analyses were carried out with Cox regression models. We stratified the risk groups based on the hazard ratios (HR).</p> <p>Results</p> <p>Both pretreatment CEA levels ≥ 10 ng/mL and SCC-Ag levels < 10 ng/mL (<it>p </it>< 0.001, HR = 8.838), SCC-Ag levels ≥ 40 ng/mL (<it>p </it>< 0.001, HR = 12.551), and SCC-Ag levels of 10-40 ng/mL (<it>p </it>< 0.001, HR = 4.2464) were significant factors for PALN recurrence. The corresponding 5-year PALN recurrence rates were 51.5%, 84.8%, and 27.5%, respectively. The 5-year PALN recurrence rate for patients with both low (< 10 ng/mL) SCC and CEA was only 9.6%. CEA levels ≥ 10 ng/mL or SCC-Ag levels ≥ 10 ng/mL at PALN recurrence were associated with overall survival after an isolated PALN recurrence. Pretreatment CEA levels ≥ 10 ng/mL were also associated with survival after an isolated PALN recurrence.</p> <p>Conclusions</p> <p>Pretreatment CEA ≥ 10 ng/mL is an additional risk factor of PALN relapse following definitive CCRT for SCC of the uterine cervix in patients with pretreatment SCC-Ag levels < 10 ng/mL. More comprehensive examinations before CCRT and intensive follow-up schedules are suggested for early detection and salvage in patients with SCC-Ag or CEA levels ≥ 10 ng/mL.</p

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions

Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10−12 in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10−6 from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10−7), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

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

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies