52% Yes, a signiicant crisis 3% No, there is no crisis 7% Don't know 38% Yes, a slight crisis 38% Yes, a slight crisis 1,576 RESEARCHERS SURVEYED M ore than 70% of researchers have tried and failed to reproduce another scientist's experiments, and more than half have failed to reproduce their own experiments. Those are some of the telling figures that emerged from Nature's survey of 1,576 researchers who took a brief online questionnaire on reproducibility in research. The data reveal sometimes-contradictory attitudes towards reproduc-ibility. Although 52% of those surveyed agree that there is a significant 'crisis' of reproducibility, less than 31% think that failure to reproduce published results means that the result is probably wrong, and most say that they still trust the published literature. Data on how much of the scientific literature is reproducible are rare and generally bleak. The best-known analyses, from psychology 1 and cancer biology 2 , found rates of around 40% and 10%, respectively. Our survey respondents were more optimistic: 73% said that they think that at least half of the papers in their field can be trusted, with physicists and chemists generally showing the most confidence. The results capture a confusing snapshot of attitudes around these issues, says Arturo Casadevall, a microbiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. "At the current time there is no consensus on what reproducibility is or should be. " But just recognizing that is a step forward, he says. "The next step may be identifying what is the problem and to get a consensus. "
Histopathology is insufficient to predict disease progression and clinical outcome in lung adenocarcinoma. Here we show that gene-expression profiles based on microarray analysis can be used to predict patient survival in early-stage lung adenocarcinomas. Genes most related to survival were identified with univariate Cox analysis. Using either two equivalent but independent training and testing sets, or 'leave-one-out' cross-validation analysis with all tumors, a risk index based on the top 50 genes identified low-risk and high-risk stage I lung adenocarcinomas, which differed significantly with respect to survival. This risk index was then validated using an independent sample of lung adenocarcinomas that predicted high- and low-risk groups. This index included genes not previously associated with survival. The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.
Highlights d A single-cell EC atlas of healthy murine tissues d This study provides an interactive webtool for comparative analyses and data exploration d Characterization of inter-and intra-tissue EC heterogeneity d Discovery tool for characterization of ECs in other datasets
Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC.
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.
7373wileyonlinelibrary.com communication, wide spectral switches or memory storage through the use of single detector. During the light communication, in order to improve the transmission rate and increase the transmission capacity, the wide spectrum photodetection is necessary. In the case of ultraviolet-visible light communication, the photodetectors can be used in the sunlight and other illumination light which is in our daily lives. By utilizing the harmless characteristics of entire visible light, the visible photodetector is expected to be a promising candidate of high-power infrastructure for indoor/outdoor public ubiquitous data communication technology in the near future. So far, studies about photodetectors were mainly focused on their performances under special wavelength, due to the lack of proper materials which have the ability to absorb of incident radiation over broad wavelength range with excellent optoelectronic transfer effi ciency. To expand the wavelength range of operation and obtain the enhanced properties, efforts have been devoted to design the photodetectors with wide spectral sensitivity through the combination of several different functional materials, which undergoes complicated fabrication process and requires expensive equipment (chemical vapor deposition, thermal evaporation, and so on), thus drawing back their applications. For example, the carbon nanotube/TiO 2 core-shell nanowires with broadband lightharvesting ability were grown through the atomic layer deposition (ALD) method by controlling the TiCl 4 /H 2 O fl ow rate at 0.25 Å/cycles after preheated carbon nanotube in the ALD reactor chamber. [ 5 ] The expensive equipment and complicated fabrication processes will undoubtedly restrict their extensive applications. Thus, searching for proper materials with wide spectral sensitivity and easy assembly is urgently needed in the area of photodetectors.Bearing this in mind, we paid our attention to the hybrid organolead halide perovskites with a general formula of (RNH 3 ) MX 3 (R = C n H 2n+1 ; X = halogen I, Br, Cl; M = Pb, Cd, Sn and so on), which have attracted signifi cant interests in electronic and photonic applications recently, [6][7][8][9][10][11] owing to their appropriate direct bandgap, [ 12 ] large absorption coeffi cient, [ 13 ] long range balanced electron and hole-transport lengths, [ 14,15 ] high electrical mobility, [ 16,17 ] and so on. Furthermore, the series of (RNH 3 )MX 3 perovskites can be fabricated by a simple and costeffective solution-based self-assembly method, rendering the (RNH 3 )MX 3 to be a competitive candidate for the application Organolead halide perovskites have attracted extensive attentions as light harvesting materials for solar cells recently, because of its high chargecarrier mobilities, high photoconversion effi ciencies, low energy cost, ease of deposition, and so on. Herein, with CH 3 NH 3 PbI 3 fi lm deposited on fl exible ITO coated substrate, the fi rst organolead halide perovskite based broadband photodetector is demonstrated. The ...
Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. Methods All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People's Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18-86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1-6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. Findings The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3-4 days. Conclusion SARS-CoV-2 infection can be confirmed based on the patient's history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.
Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was noncovalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.
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