2,400 research outputs found
Income Smoothing over the Business Cycle: Changes in Banks’ Coordinated Management of Provisions for Loan Losses and Loan Charge-offs from the Pre-1990 Bust to the 1990s Boom
We provide evidence that banks smooth income by managing provisions for loan losses and loan charge-offs in a coordinated fashion that varies across the bust and boom phases of the business cycle and across homogeneous and heterogeneous loan types. In particular, during the 1990s boom, we predict and find that banks accelerated provisioning for loan losses and made this less obvious by accelerating loan charge-offs, especially for homogenous loans for which charge-offs are determined using number-of-days-past-due rules. We also provide evidence that the valuation implications of banks’ provisions for loan losses and loan charge-offs vary across the phases of the business cycle and loan types reflecting the effect of these factors on banks’ income smoothing. In particular, during the 1990s boom, we predict and find that charge-offs of homogenous loans have a positive association with current returns and future cash flows, because these charge-offs are recorded primarily by healthy banks with good future prospects reducing over-stated allowances for loan losses. We also predict and find that these charge-offs have a positive association with future returns that is explained by their positive association with future net income and recoveries. Our results are consistent with the market only partially appreciating healthy banks’ overstatement of charge-offs of homogeneous loans based on number-of-days-past-due rules during the 1990s boom, because of the perceived non-discretionary nature of these charge-offs
Temporal Subsampling Diminishes Small Spatial Scales in Recurrent Neural Network Emulators of Geophysical Turbulence
The immense computational cost of traditional numerical weather and climate
models has sparked the development of machine learning (ML) based emulators.
Because ML methods benefit from long records of training data, it is common to
use datasets that are temporally subsampled relative to the time steps required
for the numerical integration of differential equations. Here, we investigate
how this often overlooked processing step affects the quality of an emulator's
predictions. We implement two ML architectures from a class of methods called
reservoir computing: (1) a form of Nonlinear Vector Autoregression (NVAR), and
(2) an Echo State Network (ESN). Despite their simplicity, it is well
documented that these architectures excel at predicting low dimensional chaotic
dynamics. We are therefore motivated to test these architectures in an
idealized setting of predicting high dimensional geophysical turbulence as
represented by Surface Quasi-Geostrophic dynamics. In all cases, subsampling
the training data consistently leads to an increased bias at small spatial
scales that resembles numerical diffusion. Interestingly, the NVAR architecture
becomes unstable when the temporal resolution is increased, indicating that the
polynomial based interactions are insufficient at capturing the detailed
nonlinearities of the turbulent flow. The ESN architecture is found to be more
robust, suggesting a benefit to the more expensive but more general structure.
Spectral errors are reduced by including a penalty on the kinetic energy
density spectrum during training, although the subsampling related errors
persist. Future work is warranted to understand how the temporal resolution of
training data affects other ML architectures
On-stack replacement, distilled
On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations
Pathophysiology, treatment, and animal and cellular models of human ischemic stroke
Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions
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The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.
In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests
Collider signals from slow decays in supersymmetric models with an intermediate-scale solution to the mu problem
The problem of the origin of the mu parameter in the Minimal Supersymmetric
Standard Model can be solved by introducing singlet supermultiplets with
non-renormalizable couplings to the ordinary Higgs supermultiplets. The
Peccei-Quinn symmetry is broken at a scale which is the geometric mean between
the weak scale and the Planck scale, yielding a mu term of the right order of
magnitude and an invisible axion. These models also predict one or more singlet
fermions which have electroweak-scale masses and suppressed couplings to MSSM
states. I consider the case that such a singlet fermion, containing the axino
as an admixture, is the lightest supersymmetric particle. I work out the
relevant couplings in several of the simplest models of this type, and compute
the partial decay widths of the next-to-lightest supersymmetric particle
involving leptons or jets. Although these decays will have an average proper
decay length which is most likely much larger than a typical collider detector,
they can occasionally occur within the detector, providing a striking signal.
With a large sample of supersymmetric events, there will be an opportunity to
observe these decays, and so gain direct information about physics at very high
energy scales.Comment: 24 pages, LaTeX, 4 figure
Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy
Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders
Temporal Ordering in Endocytic Clathrin-Coated Vesicle Formation via AP2 Phosphorylation.
Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. μ2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2's cargo affinity in vitro. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with μ2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME
Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a RhoD190N mutation
D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis. Wild type (wt) and mutant rhodopsin appeared correctly localized in rod outer segments of D190N heterozygotes. Moreover, the rhodopsin glycosylation state in the mutants appeared similar to that in wt mice. Thus, it seems plausible that the injurious effect of the heterozygous mutation is not related to mistrafficking of the protein, but rather from constitutive rhodopsin activity and a greater propensity for chromophore isomerization even in the absence of light.We greatly appreciate the assistance of the members of the Bernard & Shirlee Brown Glaucoma laboratory, especially to Chun-Wei Hsu for technical support. SHT is a Burroughs-Wellcome Program in Biomedical Sciences Fellow, and is also supported by the Charles E. Culpeper-Partnership for Cures 07-CS3, Crowley Research Fund, Schneeweiss Stem Cell Fund, New York State N09G-302, Foundation Fighting Blindness [TA-NMT-0116-0692- COLU] (Owings Mills, MD), TS080017 from US Department of Defense, NIH Grants [P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437], Research to Prevent Blindness (New York, NY), and Joel Hoffmann Scholarship. CSL is the Homer McK. Rees Scholar. JSP is a BEST2016 awardee (BEST/ 2016/030, Conselleria de Educación, Investigación, Cultura y Deporte; Generalitat Valenciana) and his research is supported by a Prometeo Grant (PROMETEO/2016/094; Conselleria de Educación, Investigación, Cultura y Deporte; Generalitat Valenciana) and by internal funds from Universidad Católica de Valencia San Vicente Mártir (2018-128-001). VBM is supported by NIH Grants K08EY020530, R01EY016822, The Doris Duke Charitable Foundation Grant #2013103, and Research to Prevent Blindness (New York, NY); GV is supported by NIH Grants [F30EYE027986 and T32GM007337].Author manuscriptMedicin
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