The landscape of kinase fusions in cancer Stransky, Nicolas; Cerami, Ethan; Schalm, Stefanie ...
Nature communications,
09/2014, Letnik:
5, Številka:
1
Journal Article
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Human cancer genomes harbour a variety of alterations leading to the deregulation of key pathways in tumour cells. The genomic characterization of tumours has uncovered numerous genes recurrently ...mutated, deleted or amplified, but gene fusions have not been characterized as extensively. Here we develop heuristics for reliably detecting gene fusion events in RNA-seq data and apply them to nearly 7,000 samples from The Cancer Genome Atlas. We thereby are able to discover several novel and recurrent fusions involving kinases. These findings have immediate clinical implications and expand the therapeutic options for cancer patients, as approved or exploratory drugs exist for many of these kinases.
Objective The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. Methods We performed a ...retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or heart transplant, were colonized with Burkholderia cenocepacia , or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Results Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass ( P = .32). Conclusions Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.
The Conditional Tail Expectation (CTE), also known as the Expected Shortfall and Tail-VaR, has received much attention as a preferred risk measure in finance and insurance applications. A related ...risk management exercise is to allocate the amount of the CTE computed for the aggregate or portfolio risk into individual risk units, a procedure known as the CTE allocation. In this paper we derive analytic formulas of the CTE and its allocation for the class of multivariate normal mean–variance mixture (NMVM) distributions, which is known to be extremely flexible and contains many well-known special cases as its members. We also develop the closed-form expression of the conditional tail variance (CTV) for the NMVM class, an alternative risk measure proposed in the literature to supplement the CTE by capturing the tail variability of the underlying distribution. To illustrate our findings, we focus on the multivariate Generalized Hyperbolic Distribution (GHD) family which is a popular subclass of the NMVM in connection with Lévy processes and contains some common distributions for financial modelling. In addition, we also consider the multivariate slash distribution which is not a member of GHD family but still belongs to the NMVM class. Our result is an extension of the recent contribution of Ignatieva and Landsman (2015).
In real applications, it is necessary to classify new unseen classes that cannot be acquired in training datasets. To solve this problem, few-shot learning methods are usually adopted to recognize ...new categories with only a few (out-of-bag) labeled samples together with the known classes available in the (large-scale) training dataset. Unlike common scene classification images obtained by CCD (Charge-Coupled Device) cameras, remote sensing scene classification datasets tend to have plentiful texture features rather than shape features. Therefore, it is important to extract more valuable texture semantic features from a limited number of labeled input images. In this paper, a multi-scale feature fusion network for few-shot remote sensing scene classification is proposed by integrating a novel self-attention feature selection module, denoted as SAFFNet. Unlike a pyramidal feature hierarchy for object detection, the informative representations of the images with different receptive fields are automatically selected and re-weighted for feature fusion after refining network and global pooling operation for a few-shot remote sensing classification task. Here, the feature weighting value can be fine-tuned by the support set in the few-shot learning task. The proposed model is evaluated on three publicly available datasets for few shot remote sensing scene classification. Experimental results demonstrate the effectiveness of the proposed SAFFNet to improve the few-shot classification accuracy significantly compared to other few-shot methods and the typical multi-scale feature fusion network.
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Engineering of three-dimensional (3D) tissues is a promising approach for restoring diseased or dysfunctional myocardium with a functional replacement. However, a major bottleneck in ...this field is the lack of efficient vascularization strategies, because tissue constructs produced in vitro require a constant flow of oxygen and nutrients to maintain viability and functionality. Compared to angiogenic cell therapy and growth factor treatment, bioengineering approaches such as spatial micropatterning, integration of sacrificial materials, tissue decellularization, and 3D bioprinting enable the generation of more precisely controllable neovessel formation. In this review, we summarize the state-of-the-art approaches to develop 3D tissue engineered constructs with vasculature, and demonstrate how some of these techniques have been applied towards regenerative medicine for treatment of heart failure.
Tissue engineering is a promising approach to replace or restore dysfunctional tissues/organs, but a major bottleneck in realizing its potential is the challenge of creating scalable 3D tissues. Since most 3D engineered tissues require a constant supply of nutrients, it is necessary to integrate functional vasculature within the tissues in order to facilitate the transport of nutrients. To address these needs, researchers are employing biomaterial engineering and design strategies to foster vessel formation within 3D tissues. This review highlights the state-of-the-art bioengineering tools and technologies to create vascularized 3D tissues for clinical applications in regenerative medicine, highlighting the application of these technologies to engineer vascularized cardiac patches for treatment of heart failure.
The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further ...dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.
To generate and evaluate synthesized postoperative OCT images of epiretinal membrane (ERM) based on preoperative OCT images using deep learning methodology. This study included a total 500 pairs of ...preoperative and postoperative optical coherence tomography (OCT) images for training a neural network. 60 preoperative OCT images were used to test the neural networks performance, and the corresponding postoperative OCT images were used to evaluate the synthesized images in terms of structural similarity index measure (SSIM). The SSIM was used to quantify how similar the synthesized postoperative OCT image was to the actual postoperative OCT image. The Pix2Pix GAN model was used to generate synthesized postoperative OCT images. Total 60 synthesized OCT images were generated with training values at 800 epochs. The mean SSIM of synthesized postoperative OCT to the actual postoperative OCT was 0.913. Pix2Pix GAN model has a possibility to generate predictive postoperative OCT images following ERM removal surgery.
Stem cell therapy is a promising approach for the treatment of tissue ischemia associated with myocardial infarction and peripheral arterial disease. Stem and progenitor cells derived from bone ...marrow or from pluripotent stem cells have shown therapeutic benefit in boosting angiogenesis as well as restoring tissue function. Notably, adult stem and progenitor cells including mononuclear cells, endothelial progenitor cells, and mesenchymal stem cells have progressed into clinical trials and have shown positive benefits. In this review, we overview the major classes of stem and progenitor cells, including pluripotent stem cells, and summarize the state of the art in applying these cell types for treating myocardial infarction and peripheral arterial disease.
•This paper evaluates energy saving technologies for a complex manufacturing building.•High efficiency air handling units, chillers, and advanced lighting systems are used.•Energy efficient equipment ...considered decrease a total energy cost by 14%.•Energy saving technologies will increase economic and environmental benefits to owners.
Energy saving strategies are vital for long term viability and commercial success of buildings. Buildings in the US today consume 41% of the total primary energy. Complex buildings consume significantly higher energy than typical office buildings and present challenges to energy savings due to their operational requirements. This paper presents an economic analysis on energy saving technologies implemented in a complex manufacturing building. The return on investment is determined by using the payback analysis and life cycle cost analysis. The results indicate that energy saving technologies achieved a total energy cost savings of 14%. The savings were achieved by using high efficiency HVAC equipment and advanced fluorescent lighting systems. When applied to similar types of buildings, energy saving strategies considered will increase economic and environmental benefits to owners.
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