53 research outputs found

    Securitization and mortgage default

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    The academic literature, the popular press, and policymakers have all debated securitization's contribution to the poor performance of mortgages originated in the run-up to the recent crisis. Theoretical arguments have been advanced on both sides, but the lack of suitable data has made it difficult to assess them empirically. The author examines this issue by using a loan-level data set from LPS Analytics, covering approximately two-thirds of the mortgages originated in 2005 and 2006, and including both securitized and nonsecuritized loans. ; The author finds evidence that privately securitized loans do indeed perform worse than observably similar, nonsecuritized loans. Moreover, this effect is strongest in prime mortgage markets, which have not been studied in the previous literature. For example, a typical prime loan becomes delinquent at a 20 percent higher rate if it is privately securitized, ceteris paribus. This is consistent with the existence of adverse selection; that is, that lenders used information not available to investors to securitize loans that were riskier than they otherwise appeared. By contrast, for subprime mortgages, the impact of private securitization is concentrated in low or no-documentation loans; this latter result is consistent with previous work such as Keys et al. (2009).Mortgage-backed securities ; Default (Finance)

    Role of Risk Stratification and Genetics in Sudden Cardiac Death

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    Sudden cardiac death (SCD) is a major public health issue due to its increasing incidence in the general population and the difficulty in identifying high-risk individuals. Nearly 300,000-350,000 patients in the United States and 4- to 5 million patients in the world die from SCD. Coronary artery disease and advanced heart failure are the main etiology for SCD. Ischemia of any cause precipitates lethal arrhythmias, and ventricular tachycardia and ventricular fibrillation are the most common lethal arrhythmias precipitating SCD. Pulse-less electrical activity, brady-arrhythmia and electromechanical dissociation also result in SCD. Most sudden cardiac deaths occur out-of-the-hospital setting, so it is difficult to estimate the public burden, which results in overestimating the incidence of SCD. The insufficiency and limited predictive value of various indicators and criteria for SCD result in the increasing incidences. As a result, there is a need to develop better risk stratification criteria and find modifiable variables to decrease the incidence. Primary and secondary prevention and treatment of SCD need further research. This critical review is focused on the etiology, risk factors, prognostic factors and importance of risk stratification of SCD.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    TALENs—an indispensable tool in the era of CRISPR: a mini review

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    Abstract Background Genome of an organism has always fascinated life scientists. With the discovery of restriction endonucleases, scientists were able to make targeted manipulations (knockouts) in any gene sequence of any organism, by the technique popularly known as genome engineering. Though there is a range of genome editing tools, but this era of genome editing is dominated by the CRISPR/Cas9 tool due to its ease of design and handling. But, when it comes to clinical applications, CRISPR is not usually preferred. In this review, we will elaborate on the structural and functional role of designer nucleases with emphasis on TALENs and CRISPR/Cas9 genome editing system. We will also present the unique features of TALENs and limitations of CRISPRs which makes TALENs a better genome editing tool than CRISPRs. Main body Genome editing is a robust technology used to make target specific DNA modifications in the genome of any organism. With the discovery of robust programmable endonucleases-based designer gene manipulating tools such as meganucleases (MN), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats associated protein (CRISPR/Cas9), the research in this field has experienced a tremendous acceleration giving rise to a modern era of genome editing with better precision and specificity. Though, CRISPR-Cas9 platform has successfully gained more attention in the scientific world, TALENs and ZFNs are unique in their own ways. Apart from high-specificity, TALENs are proven to target the mitochondrial DNA (mito-TALEN), where gRNA of CRISPR is difficult to import. This review talks about genome editing goals fulfilled by TALENs and drawbacks of CRISPRs. Conclusions This review provides significant insights into the pros and cons of the two most popular genome editing tools TALENs and CRISPRs. This mini review suggests that, TALENs provides novel opportunities in the field of therapeutics being highly specific and sensitive toward DNA modifications. In this article, we will briefly explore the special features of TALENs that makes this tool indispensable in the field of synthetic biology. This mini review provides great perspective in providing true guidance to the researchers working in the field of trait improvement via genome editing

    KasI vs. SspDI: Comparative analysis of enzyme activity for restriction digestion

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    945-948Type II restriction enzymes are routinely used by molecular biologists in designing and implementation of cloning experiments without referring to the literature on enzymes in use, and at times, face some unforeseeable problems. In our laboratory too, we encountered one such problem while working with KasI restriction enzyme which recognizes GGCGCC sequence, and we further analyzed the issue. Our observations corroborate the fact that KasI acts as monomer and cleaves double stranded DNA through nicking mechanism. It introduces breaks in two strands of DNA after substantial time gap which can be owed to two independent nickase activities in the opposite strands. Moreover, this time gap between two nickase activities results in formation of different topological forms of DNA. Since molecular biologists working with common restriction enzymes are not familiar with such nickase activity, they may misinterpret their restriction digestion results. However, no such problem was observed with the use of SspDI restriction enzyme which also recognizes the same sequence (GGCGCC) and produces the identical overhangs as by KasI. Hence, SspDI suits better for routine cloning and genetic modification purposes over KasI while using GGCGCC as cloning site

    CPP-ZFN: A potential DNA-targeting anti-malarial drug

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    Abstract Background Multidrug-resistant Plasmodium is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death. Presentation of the hypothesis Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells. Testing the hypothesis Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the Plasmodium genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between Plasmodium and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to Plasmodium-infected RBCs (iRBCs) and different Plasmodium organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more Plasmodium cell membrane translocation peptide seems achievable. Implications of the hypothesis Targeting of the Plasmodium genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

    Plate Heat Exchanger Optimization Using Different Approximation Assisted Multiobjective Optimization Techniques

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    This paper presents a comparison between different multiobjective optimization approaches that can be used to optimize the design of thermal equipment. Plate heat exchanger is taken as case study to apply different optimization techniques. The thermal-hydrodynamic characteristics of single phase turbulent flow in chevron-type plate heat exchangers with sinusoidal-shaped corrugations have been used in this paper. The computational domain contains a corrugation channel and the simulations adopted the shear-stress transport (SST) κ-ω model as the turbulence model. Two different approximation assisted optimization approaches are tested. Offline approximation assisted optimization, and online approximation assisted optimization are compared to optimize plate heat exchanger design. For both approximation techniques (offline and online), design optimization is performed using multiobjective genetic algorithm based on meta-models that are built to represent the entire design space. In offline approximation, globally accurate meta-models are built which requires adding more samples. However in online approximation assisted optimization, samples are added just to improve the metamodels performance in the expected optimum region. Approximated optimum designs are validated using computationally expensive actual CFD simulations. Finally, a comparison between offline and online approximation assisted optimization is presented with guidelines to apply both approaches in the area of heat exchanger design optimization. The methods presented in this paper are generic and can be applied to optimize different types of heat exchangers, electronic cooling devices and other thermal system components

    A novel approach to MP-PIC: Continuum particle model for dense particle flows in fluidized beds

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    A novel approach to Multiphase-Particle-in-Cell (MP-PIC), called Continuum Particle Model (CPM), is developed for dense gas-particle flows. CPM has high computational speed, comparable to that of MP-PIC, but a robustness and accuracy closer to that of a Discrete Element Model (DEM). The gas phase is treated as a continuum phase and particles are tracked discretely, but particle collisions are modelled by considering the divergence of the continuum particle stress tensor. Details on efficient solution to the model are presented. For comparison, a parametric study is performed for quasi-2D fluidized beds. Comparison of CFD-CPM is made with MP-PIC and CFD-DEM. The particle stress models by Harris and Crighton, and by Srivastava and Sundaresan are tested in our CFD-CPM. Results from CFD-CPM based on the Srivastava and Sundaresan particle stress model show good agreement with CFD-DEM results. We validate our model by comparison with experimental benchmark results from Gopalan et. al. (2016).Complex Fluid Processin
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