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Showing papers by "Sun Yat-sen University published in 2014"


Journal ArticleDOI
Jun-Hao Li1, Shun Liu1, Hui Zhou1, Liang-Hu Qu1, Jian-Hua Yang1 
TL;DR: This study developed starBase v2.0, which has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and mi RNA-lncRNA interaction networks to date, and developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from themiRNA-mediated regulatory networks.
Abstract: Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs. In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA-RNA and protein-RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies. By analyzing millions of RNA-binding protein binding sites, we identified ∼9000 miRNA-circRNA, 16 000 miRNA-pseudogene and 285,000 protein-RNA regulatory relationships. Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified ∼10,000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNA-mediated regulatory networks. Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets. This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.

3,597 citations


Proceedings Article
27 Jul 2014
TL;DR: This paper proposes TransH which models a relation as a hyperplane together with a translation operation on it and can well preserve the above mapping properties of relations with almost the same model complexity of TransE.
Abstract: We deal with embedding a large scale knowledge graph composed of entities and relations into a continuous vector space. TransE is a promising method proposed recently, which is very efficient while achieving state-of-the-art predictive performance. We discuss some mapping properties of relations which should be considered in embedding, such as reflexive, one-to-many, many-to-one, and many-to-many. We note that TransE does not do well in dealing with these properties. Some complex models are capable of preserving these mapping properties but sacrifice efficiency in the process. To make a good trade-off between model capacity and efficiency, in this paper we propose TransH which models a relation as a hyperplane together with a translation operation on it. In this way, we can well preserve the above mapping properties of relations with almost the same model complexity of TransE. Additionally, as a practical knowledge graph is often far from completed, how to construct negative examples to reduce false negative labels in training is very important. Utilizing the one-to-many/many-to-one mapping property of a relation, we propose a simple trick to reduce the possibility of false negative labeling. We conduct extensive experiments on link prediction, triplet classification and fact extraction on benchmark datasets like WordNet and Freebase. Experiments show TransH delivers significant improvements over TransE on predictive accuracy with comparable capability to scale up.

2,835 citations


Journal ArticleDOI
Jiewei Liu1, Lianfen Chen1, Hao Cui1, Jianyong Zhang1, Li Zhang1, Cheng-Yong Su1 
TL;DR: This review summarizes the use of metal-organic frameworks (MOFs) as a versatile supramolecular platform to develop heterogeneous catalysts for a variety of organic reactions, especially for liquid-phase reactions.
Abstract: This review summarizes the use of metal–organic frameworks (MOFs) as a versatile supramolecular platform to develop heterogeneous catalysts for a variety of organic reactions, especially for liquid-phase reactions. Following a background introduction about catalytic relevance to various metal–organic materials, crystal engineering of MOFs, characterization and evaluation methods of MOF catalysis, we categorize catalytic MOFs based on the types of active sites, including coordinatively unsaturated metal sites (CUMs), metalloligands, functional organic sites (FOS), as well as metal nanoparticles (MNPs) embedded in the cavities. Throughout the review, we emphasize the incidental or deliberate formation of active sites, the stability, heterogeneity and shape/size selectivity for MOF catalysis. Finally, we briefly introduce their relevance into photo- and biomimetic catalysis, and compare MOFs with other typical porous solids such as zeolites and mesoporous silica with regard to their different attributes, and provide our view on future trends and developments in MOF-based catalysis.

2,418 citations


Journal ArticleDOI
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.

1,383 citations


Journal ArticleDOI
TL;DR: This review describes the most recent advances in flexible energy-storage devices, including flexible lithium-ion batteries and flexible supercapacitors, based on carbon materials and a number of composites and flexible micro-supercapacitor.
Abstract: Flexible energy-storage devices are attracting increasing attention as they show unique promising advantages, such as flexibility, shape diversity, light weight, and so on; these properties enable applications in portable, flexible, and even wearable electronic devices, including soft electronic products, roll-up displays, and wearable devices. Consequently, considerable effort has been made in recent years to fulfill the requirements of future flexible energy-storage devices, and much progress has been witnessed. This review describes the most recent advances in flexible energy-storage devices, including flexible lithium-ion batteries and flexible supercapacitors. The latest successful examples in flexible lithium-ion batteries and their technological innovations and challenges are reviewed first. This is followed by a detailed overview of the recent progress in flexible supercapacitors based on carbon materials and a number of composites and flexible micro-supercapacitors. Some of the latest achievements regarding interesting integrated energy-storage systems are also reviewed. Further research direction is also proposed to surpass existing technological bottle-necks and realize idealized flexible energy-storage devices.

1,107 citations


Journal ArticleDOI
TL;DR: Flexible solid-state supercapacitors (SCs) have attracted increasing interest because they can provide substantially higher specific/volumetric energy density compared to conventional capacitors.
Abstract: Increasing power and energy demands for next-generation portable and flexible electronics such as roll-up displays, photovoltaic cells, and wearable devices have stimulated intensive efforts to explore flexible, lightweight and environmentally friendly energy storage devices. Flexible solid-state supercapacitors (SCs) have attracted increasing interest because they can provide substantially higher specific/volumetric energy density compared to conventional capacitors. Additionally, flexible solid-state SCs are typically small in size, highly reliable, light-weight, easy to handle, and have a wide range of operation temperatures. In this regard, solid-state SCs hold great promise as new energy storage devices for flexible and wearable electronics. In this article, we review recent achievements in the design, fabrication and characterization of flexible solid-state SCs. Moreover, we also discuss the current challenges and future opportunities for the development of high-performance flexible solid-state SCs.

1,105 citations


Journal ArticleDOI
13 Feb 2014-Cell
TL;DR: By coinjection of Cas9 mRNA and sgRNAs into one-cell-stage embryos, this system successfully achieves precise gene targeting in cynomolgus monkeys and enables simultaneous disruption of two target genes in one step, and no off-target mutagenesis was detected by comprehensive analysis.

950 citations


Proceedings Article
27 Jul 2014
TL;DR: Extensive empirical evaluations on three benchmark datasets with different kinds of images show that the proposed method has superior performance gains over several state-of-the-art supervised and unsupervised hashing methods.
Abstract: Hashing is a popular approximate nearest neighbor search approach for large-scale image retrieval. Supervised hashing, which incorporates similarity/ dissimilarity information on entity pairs to improve the quality of hashing function learning, has recently received increasing attention. However, in the existing supervised hashing methods for images, an input image is usually encoded by a vector of handcrafted visual features. Such hand-crafted feature vectors do not necessarily preserve the accurate semantic similarities of images pairs, which may often degrade the performance of hashing function learning. In this paper, we propose a supervised hashing method for image retrieval, in which we automatically learn a good image representation tailored to hashing as well as a set of hash functions. The proposed method has two stages. In the first stage, given the pairwise similarity matrix S over training images, we propose a scalable coordinate descent method to decompose S into a product of HHT where H is a matrix with each of its rows being the approximate hash code associated to a training image. In the second stage, we propose to simultaneously learn a good feature representation for the input images as well as a set of hash functions, via a deep convolutional network tailored to the learned hash codes in H and optionally the discrete class labels of the images. Extensive empirical evaluations on three benchmark datasets with different kinds of images show that the proposed method has superior performance gains over several state-of-the-art supervised and unsupervised hashing methods.

925 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

875 citations


Journal ArticleDOI
01 May 2014-Nature
TL;DR: Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking, and novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC are explored.
Abstract: Oesophageal cancer is one of the most aggressive cancers and is the sixth leading cause of cancer death worldwide(1). Approximately 70% of global oesophageal cancer cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the histopathological form in the vast majority of cases (>90%)(2,3). Currently, there are limited clinical approaches for the early diagnosis and treatment of ESCC, resulting in a 10% five-year survival rate for patients. However, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of the International Cancer Genome Consortium research project. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and whole-exome sequencing, were subjected to array comparative genomic hybridization analysis. We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B). Notably, FAM135B is identified as a novel cancer-implicated gene as assayed for its ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA encoded in the amplified 11q13.3-13.4 region, is characterized as a novel oncogene, and functional assays demonstrate that MIR548K enhances malignant phenotypes of ESCC cells. Moreover, we have found that several important histone regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP and EP300) are frequently altered in ESCC. Pathway assessment reveals that somatic aberrations are mainly involved in the Wnt, cell cycle and Notch pathways. Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking. This study has explored novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC.

853 citations


Journal ArticleDOI
M. Aguilar, D. Aisa1, Behcet Alpat, A. Alvino  +291 moreInstitutions (33)
TL;DR: In this paper, a precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1.GV to 1.8TV is presented based on 300 million events.
Abstract: A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the flux spectral index for the first time. The spectral index progressively hardens at high rigidities.

Journal ArticleDOI
TL;DR: The asymmetric-supercapacitor device based on the oxygen-deficient α-Fe2 O3 nanorod negative electrode and a MnO2 positive electrode achieves a maximum energy density of 0.41 mW·h/cm(3) and is capable of charging a mobile phone and powering a light-emitting diode indicator.
Abstract: Oxygen-deficient α-Fe2 O3 nanorods with outstanding capacitive performance are developed and demonstrated as novel negative electrodes for flexible asymmetric supercapacitors. The asymmetric-supercapacitor device based on the oxygen-deficient α-Fe2 O3 nanorod negative electrode and a MnO2 positive electrode achieves a maximum energy density of 0.41 mW·h/cm(3) ; it is also capable of charging a mobile phone and powering a light-emitting diode indicator.

Journal ArticleDOI
TL;DR: A molecular link between epithelial-to-mesenchymal transition (EMT) and CD8+ TIL immunosuppression and cancer progression is demonstrated and ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.
Abstract: Immunosuppression of tumour-infiltrating lymphocytes (TIL) is a common feature of advanced cancer, but its biological basis has remained obscure. We demonstrate here a molecular link between epithelial-to-mesenchymal transition (EMT) and CD8(+) TIL immunosuppression, two key drivers of cancer progression. We show that microRNA-200 (miR-200), a cell-autonomous suppressor of EMT and metastasis, targets PD-L1. Moreover, ZEB1, an EMT activator and transcriptional repressor of miR-200, relieves miR-200 repression of PD-L1 on tumour cells, leading to CD8(+) T-cell immunosuppression and metastasis. These findings are supported by robust correlations between the EMT score, miR-200 levels and PD-L1 expression in multiple human lung cancer datasets. In addition to revealing a link between EMT and T-cell dysfunction, these findings also show that ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and suggest that subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.

Journal ArticleDOI
TL;DR: This study is the first to demonstrate the contributions of different reactive species to the micropollutant degradation in the UV/chlorine system under environmentally relevant conditions.
Abstract: The UV/free chlorine process forms reactive species such as hydroxyl radicals (HO•), chlorine atoms (Cl•), Cl2•–, and O•–. The specific roles of these reactive species in aqueous micropollutant degradation in the UV/chlorine process under different conditions were investigated using a steady-state kinetic model. Benzoic acid (BA) was chosen as the model micropollutant. The steady-state kinetic model developed fitted the experimental data well. The results showed that HO• and Cl• contributed substantially to BA degradation, while the roles of the other reactive species such as Cl2•– and O•– were negligible. The overall degradation rate of BA decreased as the pH increased from 6 to 9. In particular, the relative contributions of HO• and Cl• to the degradation changed from 34.7% and 65.3% respectively at pH 6 to 37.9% and 62% respectively at pH 9 under the conditions evaluated. Their relative contributions also changed slightly with variations in chlorine dosage, BA concentration and chloride concentration. ...

Journal ArticleDOI
TL;DR: High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside thecell as the prototypic damage associated molecular pattern molecule (DAMP).

Journal ArticleDOI
TL;DR: M. barkeri is the second methanogen found to accept electrons via DIET and the first meetinghanogen known to be capable of using either H2 or electrons derived from DIET for CO2 reduction, making it a model organism for elucidating mechanisms by which methanogens make biological electrical connections with other cells.
Abstract: Direct interspecies electron transfer (DIET) is potentially an effective form of syntrophy in methanogenic communities, but little is known about the diversity of methanogens capable of DIET. The ability of Methanosarcina barkeri to participate in DIET was evaluated in coculture with Geobacter metallireducens. Cocultures formed aggregates that shared electrons via DIET during the stoichiometric conversion of ethanol to methane. Cocultures could not be initiated with a pilin-deficient G. metallireducens strain, suggesting that long-range electron transfer along pili was important for DIET. Amendments of granular activated carbon permitted the pilin-deficient G. metallireducens isolates to share electrons with M. barkeri, demonstrating that this conductive material could substitute for pili in promoting DIET. When M. barkeri was grown in coculture with the H2-producing Pelobacter carbinolicus, incapable of DIET, M. barkeri utilized H2 as an electron donor but metabolized little of the acetate that P. carbinolicus produced. This suggested that H2, but not electrons derived from DIET, inhibited acetate metabolism. P. carbinolicus-M. barkeri cocultures did not aggregate, demonstrating that, unlike DIET, close physical contact was not necessary for interspecies H2 transfer. M. barkeri is the second methanogen found to accept electrons via DIET and the first methanogen known to be capable of using either H2 or electrons derived from DIET for CO2 reduction. Furthermore, M. barkeri is genetically tractable, making it a model organism for elucidating mechanisms by which methanogens make biological electrical connections with other cells.

Journal ArticleDOI
TL;DR: This work demonstrates a simple and general strategy to substantially enhance the cycling stability of conductive polymer electrodes by deposition of a thin carbonaceous shell onto their surface by fabricating stable polymer electrodes with comparable specific capacitance and pseudocapacitive behavior as the bare polymer electrodes.
Abstract: Conducting polymers such as polyaniline and polypyrrole have been widely used as pseudocapacitive electrode materials for supercapacitors. However, their structural instability resulting from repea...

Journal ArticleDOI
TL;DR: Activated carbon cloth is used as an electrode, achieving an excellent areal capacitance of 88mF/cm(2) (8.8 mF/g) without the use of any other capacitive materials; when incorporated as part of a symmetric solid-state supercapacitor device, a remarkable charge/discharge rate capability is observed.
Abstract: Activated carbon cloth is used as an electrode, achieving an excellent areal capacitance of 88 mF/cm(2) (8.8 mF/g) without the use of any other capacitive materials. Significantly, when it is incorporated as part of a symmetric solid-state supercapacitor device, a remarkable charge/discharge rate capability is observed; 50% of the capacitance is retained when the charging rate increases from 10 to 10,000 mV/s.

Proceedings Article
27 Jul 2014
TL;DR: This paper proposes a novel Markov chain method for Robust Multi-view Spectral Clustering (RMSC), which has a flavor of lowrank and sparse decomposition, and has superior performance over several state-of-the-art methods for multi-view clustering.
Abstract: Multi-view clustering, which seeks a partition of the data in multiple views that often provide complementary information to each other, has received considerable attention in recent years. In real life clustering problems, the data in each view may have considerable noise. However, existing clustering methods blindly combine the information from multi-view data with possibly considerable noise, which often degrades their performance. In this paper, we propose a novel Markov chain method for Robust Multi-view Spectral Clustering (RMSC). Our method has a flavor of lowrank and sparse decomposition, where we firstly construct a transition probability matrix from each single view, and then use these matrices to recover a shared low-rank transition probability matrix as a crucial input to the standard Markov chain method for clustering. The optimization problem of RMSC has a low-rank constraint on the transition probability matrix, and simultaneously a probabilistic simplex constraint on each of its rows. To solve this challenging optimization problem, we propose an optimization procedure based on the Augmented Lagrangian Multiplier scheme. Experimental results on various real world datasets show that the proposed method has superior performance over several state-of-the-art methods for multi-view clustering.

Journal ArticleDOI
TL;DR: It is shown that mesenchymal-like breast cancer cells activate macrophages to a TAM-like phenotype by GM-CSF, which suggests that a positive feedback loop between GM- CSF and CCL18 is important in breast cancer metastasis.

Journal ArticleDOI
01 Jun 2014-Leukemia
TL;DR: It is suggested that PD-1 signaling may be involved in MDS pathogenesis and resistance mechanisms to hypomethylating agents and blockade of this pathway can be a potential therapy in M DS and AML.
Abstract: Blockade of immune checkpoints is emerging as a new form of anticancer therapy. We studied the expression of programmed death ligand 1 (PD-L1), PD-L2, programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) mRNA in CD34+ cells from myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) patients (N=124). Aberrant upregulation (⩾2-fold) was observed in 34, 14, 15 and 8% of the patients. Increased expression of these four genes was also observed in peripheral blood mononuclear cells (PBMNCs) (N=61). The relative expression of PD-L1 from PBMNC was significantly higher in MDS (P=0.018) and CMML (P=0.0128) compared with AML. By immunohistochemical analysis, PD-L1 protein expression was observed in MDS CD34+ cells, whereas stroma/non-blast cellular compartment was positive for PD-1. In a cohort of patients treated with epigenetic therapy, PD-L1, PD-L2, PD-1 and CTLA4 expression was upregulated. Patients resistant to therapy had relative higher increments in gene expression compared with patients who achieved response. Treatment of leukemia cells with decitabine resulted in a dose-dependent upregulation of above genes. Exposure to decitabine resulted in partial demethylation of PD-1 in leukemia cell lines and human samples. This study suggests that PD-1 signaling may be involved in MDS pathogenesis and resistance mechanisms to hypomethylating agents. Blockade of this pathway can be a potential therapy in MDS and AML.

Journal ArticleDOI
TL;DR: This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.
Abstract: The oxidative stress imposed by reactive oxygen species (ROS) plays an important role in many chronic and degenerative diseases. As an important category of phytochemicals, phenolic compounds universally exist in plants, and have been considered to have high antioxidant ability and free radical scavenging capacity, with the mechanism of inhibiting the enzymes responsible for ROS production and reducing highly oxidized ROS. Therefore, phenolic compounds have attracted increasing attention as potential agents for preventing and treating many oxidative stress-related diseases, such as cardiovascular diseases, cancer, ageing, diabetes mellitus and neurodegenerative diseases. This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.

Journal ArticleDOI
TL;DR: The approach using angular ligand containing partially fixed TPE units paves a way toward highly porous MOFs with fluorescence turn-on response that will find wide applications in chemical sensing.
Abstract: We report a 2D layered metal–organic framework (MOF) with wide channels named NUS-1 and its activated analogue NUS-1a composed of Zn4O-like secondary building units and tetraphenylethene (TPE)-based ligand 4,4′-(2,2-diphenylethene-1,1-diyl)dibenzoic acid. Due to its special structure, NUS-1a exhibits unprecedented gas sorption behavior, glass-transition-like phase transition under cryogenic conditions, and responsive turn-on fluorescence to various volatile organic compounds. Our approach using angular ligand containing partially fixed TPE units paves a way toward highly porous MOFs with fluorescence turn-on response that will find wide applications in chemical sensing.

Journal ArticleDOI
TL;DR: The fundamentals of EPSs including definitions, compositions and properties, and factors affecting EPSs production and characteristics are summarized and based on which, EPSs control towards membrane fouling mitigation in MBRs are comprehensively discussed.

Journal ArticleDOI
S. Chatrchyan, Khachatryan1, Albert M. Sirunyan, Armen Tumasyan  +2384 moreInstitutions (207)
26 May 2014
TL;DR: In this paper, a description of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices is provided.
Abstract: A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tt events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of p_T > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of p_T = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in p_T, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung.

Journal ArticleDOI
TL;DR: Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years.
Abstract: Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40years. The failure to implant may be a consequence of embryo or uterine factors. Thorough investigations should be carried out to ascertain whether there is any underlying cause of the condition. Ovarian function should be assessed by measurement of antral follicle count, FSH and anti-Mullerian hormone. Increased sperm DNA fragmentation may be a contributory cause. Various uterine pathology including fibroids, endometrial polyps, congenital anomalies and intrauterine adhesions should be excluded by ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of implantation failure and should be excluded by hysterosalpingogram; if necessary, laparoscopy should be performed to confirm or refute the diagnosis. Treatment offered should be evidence based, aimed at improving embryo quality or endometrial receptivity. Gamete donation or surrogacy may be necessary if there is no realistic chance of success with further IVF attempts. Recurrent implantation failure is an important cause of repeated IVF failure. It is estimated that approximately 10% of women seeking IVF treatment will experience this particular problem. It is a distressing condition for patients and frustrating for clinicians and scientists. In this review, we have discussed the definition and management of the possible underlying causes of recurrent implantation failure.

Journal ArticleDOI
TL;DR: The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma, with mutations in epigenetic modulators with prognostic and potentially therapeutic implications highlighted.
Abstract: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Journal ArticleDOI
TL;DR: Diabetes is a much more heterogeneous disease than the present subdivision into types 1 and 2 assumes; type 1 and type 2 diabetes probably represent extremes on a range of diabetic disorders.

Journal ArticleDOI
L. Accardo1, M. Aguilar, D. Aisa1, D. Aisa2  +308 moreInstitutions (28)
TL;DR: The new results show, for the first time, that above ∼200 GeV the positron fraction no longer exhibits an increase with energy.
Abstract: A precision measurement by AMS of the positron fraction in primary cosmic rays in the energy range from 0.5 to 500 GeV based on 10.9 million positron and electron events is presented. This measurement extends the energy range of our previous observation and increases its precision. The new results show, for the first time, that above ∼200 GeV the positron fraction no longer exhibits an increase with energy.

Journal ArticleDOI
TL;DR: In this paper, the formation of methylammonium lead halide perovskite is likely driven by release of gaseous CH3NH3Cl (or other organic chlorides) through an intermediate organometal mixed halide phase.
Abstract: CH3NH3PbI3-xClx is a commonly used chemical formula to represent the methylammonium lead halide perovskite fabricated from mixed chlorine- and iodine-containing salt precursors. Despite the rapid progress in improving its photovoltaic efficiency, fundamental questions remain regarding the atomic ratio of Cl in the perovskite as well as the reaction mechanism that leads to its formation and crystallization. In this work we investigated these questions through a combination of chemical, morphological, structural and thermal characterizations. The elemental analyses reveal unambiguously the negligible amount of Cl atoms in the CH3NH3PbI3-xClx perovskite. By studying the thermal characteristics of methylammonium halides as well as the annealing process in a polymer/perovskite/FTO glass structure, we show that the formation of the CH3NH3PbI3-xClx perovskite is likely driven by release of gaseous CH3NH3Cl (or other organic chlorides) through an intermediate organometal mixed halide phase. Furthermore, the comparative study on CH3NH3I/PbCl2 and CH3NH3I/PbI2 precursor combinations with different molar ratios suggest that the initial introduction of a CH3NH3+ rich environment is critical to slow down the perovskite formation process and thus improve the growth of the crystal domains during annealing; accordingly, the function of Cl− is to facilitate the release of excess CH3NH3+ at a relatively low annealing temperatures.