The Risk Management Role of Accounting Conservatism for Operating Cash Flows

This study examines relations between accounting conservatism and the downside risk of operating cash flows (OCF) and finds both unconditional and conditional conservatism to be negatively associated with OCF downside risk measured by indicators of OCF falling below expectations, by OCF’s root lower partial moment and by OCF at risk, with several additional results. First, both unconditional and conditional conservatism enhance cash holdings and its upside potential, thus helping mitigate subsequent OCF downside risk. Second, both unconditional and conditional conservatism reduce the effects of customer bargaining power on OCF downside risk. Third, conditional conservatism increases hedge usage and unconditional conservatism substitutes for hedging in mitigating OCF downside risk. Finally, downside cash flow beta enhances unconditional and conditional conservatism and the mitigating effect of unconditional conservatism on OCF downside risk during economic downturns. These findings lend support to conservatism’s role as a risk management tool and are robust to alternative measures and various controls.postprin

Haplobanking induced pluripotent stem cells for clinical use

The development of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka and colleagues in 2006 has led to a potential new paradigm in cellular therapeutics, including the possibility of producing patient-specific, disease-specific and immune matched allogeneic cell therapies. One can envisage two routes to immunologically compatible iPSC therapies: using genetic modification to generate a ‘universal donor’ with reduced expression of Human Leukocyte Antigens (HLA) and other immunological targets or developing a haplobank containing iPSC lines specifically selected to provide HLA matched products to large portions of the population. HLA matched lines can be stored in a designated physical or virtual global bank termed a ‘haplobank’. The process of ‘iPSC haplobanking’ refers to the banking of iPSC cell lines, selected to be homozygous for different HLA haplotypes, from which therapeutic products can be derived and matched immunologically to patient populations. By matching iPSC and derived products to a patient’s HLA class I and II molecules, one would hope to significantly reduce the risk of immune rejection and the use of immunosuppressive medication. Immunosuppressive drugs are used in several conditions (including autoimmune disease and in transplantation procedures) to reduce rejection of infused cells, or transplanted tissue and organs, due to major and minor histocompatibility differences between donor and recipient. Such regimens can lead to immune compromise and pathological consequences such as opportunistic infections or malignancies due to decreased cancer immune surveillance. In this article, we will discuss what is practically involved if one is developing and executing an iPSC haplobanking strategy

SpikingLab: modelling agents controlled by Spiking Neural Networks in Netlogo

The scientific interest attracted by Spiking Neural Networks (SNN) has lead to the development of tools for the simulation and study of neuronal dynamics ranging from phenomenological models to the more sophisticated and biologically accurate Hodgkin-and-Huxley-based and multi-compartmental models. However, despite the multiple features offered by neural modelling tools, their integration with environments for the simulation of robots and agents can be challenging and time consuming. The implementation of artificial neural circuits to control robots generally involves the following tasks: (1) understanding the simulation tools, (2) creating the neural circuit in the neural simulator, (3) linking the simulated neural circuit with the environment of the agent and (4) programming the appropriate interface in the robot or agent to use the neural controller. The accomplishment of the above-mentioned tasks can be challenging, especially for undergraduate students or novice researchers. This paper presents an alternative tool which facilitates the simulation of simple SNN circuits using the multi-agent simulation and the programming environment Netlogo (educational software that simplifies the study and experimentation of complex systems). The engine proposed and implemented in Netlogo for the simulation of a functional model of SNN is a simplification of integrate and fire (I&F) models. The characteristics of the engine (including neuronal dynamics, STDP learning and synaptic delay) are demonstrated through the implementation of an agent representing an artificial insect controlled by a simple neural circuit. The setup of the experiment and its outcomes are described in this work

Size-Dependent Photon Emission from Organometal Halide Perovskite Nanocrystals Embedded in an Organic Matrix

10.1021/jz502615eJournal of Physical Chemistry Letters63446-45

Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients

Aim Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients. Methods and Results Venous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37). Concentrations of leptin, adipocyte fatty acid-binding protein (AFABP) and adiponectin (APN) were determined by enzyme-linked immunosorbent assays (ELISA). The median concentration of leptin in PF (4.3 (interquartile range: 2.8-9.1) mu g/L) was comparable to that in P (5.9 (2.2-11) mu g/L) and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28-124) versus 8.4 (5.2-14) mu g/L) and that of APN was markedly lower (2.8 (1.7-4.2) versus 13 (7.2-19) mg/L) in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins. Conclusion In cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.published_or_final_versio

Dual conformal constraints and infrared equations from global residue theorems in N=4 SYM theory

Infrared equations and dual conformal constraints arise as consistency conditions on loop amplitudes in N=4 super Yang-Mills theory. These conditions are linear relations between leading singularities, which can be computed in the Grassmannian formulation of N=4 super Yang-Mills theory proposed recently. Examples for infrared equations have been shown to be implied by global residue theorems in the Grassmannian picture. Both dual conformal constraints and infrared equations are mapped explicitly to global residue theorems for one-loop next-to-maximally-helicity-violating amplitudes. In addition, the identity relating the BCFW and its parity-conjugated form of tree-level amplitudes, is shown to emerge from a particular combination of global residue theorems.Comment: 21 page

A picogram and nanometer scale photonic crystal opto-mechanical cavity

We describe the design, fabrication, and measurement of a cavity opto-mechanical system consisting of two nanobeams of silicon nitride in the near-field of each other, forming a so-called "zipper" cavity. A photonic crystal patterning is applied to the nanobeams to localize optical and mechanical energy to the same cubic-micron-scale volume. The picrogram-scale mass of the structure, along with the strong per-photon optical gradient force, results in a giant optical spring effect. In addition, a novel damping regime is explored in which the small heat capacity of the zipper cavity results in blue-detuned opto-mechanical damping.Comment: 15 pages, 4 figure

Determining initial and follow-up costs of cardiovascular events in a US managed care population

<p>Abstract</p> <p>Background</p> <p>Cardiovascular (CV) events are prevalent and expensive worldwide both in terms of direct medical costs at the time of the event and follow-up healthcare after the event. This study aims to determine initial and follow-up costs for cardiovascular (CV) events in US managed care enrollees and to compare to healthcare costs for matched patients without CV events.</p> <p>Methods</p> <p>A 5.5-year retrospective matched cohort analysis of claims records for adult enrollees in ~90 US health plans. Patients hospitalized for first CV event were identified from a database containing a representative sample of the commercially-insured US population. The CV-event group (n = 29,688) was matched to a control group with similar demographics but no claims for CV-related events. Endpoints were total direct medical costs for inpatient and outpatient services and pharmacy (paid insurance amount).</p> <p>Results</p> <p>Overall, mean initial inpatient costs were US dollars ($) 16,981 per case (standard deviation [SD] =$20,474), ranging from $6,699 for a transient ischemic attack (mean length of stay [LOS] = 3.7 days) to$56,024 for a coronary artery bypass graft (CABG) (mean LOS = 9.2 days). Overall mean health-care cost during 1-year follow-up was $16,582 (SD =$34,425), an excess of $13,792 over the mean cost of matched controls. This difference in average costs between CV-event and matched-control subjects was$20,862 and $26,014 after two and three years of follow-up. Mean overall inpatient costs for second events were similar to those for first events ($17,705/case; SD = $22,703). The multivariable regression model adjusting for demographic and clinical characteristics indicated that the presence of a CV event was positively associated with total follow-up costs (P < 0.0001).</p> <p>Conclusions</p> <p>Initial hospitalization and follow-up costs vary widely by type of CV event. The 1-year follow-up costs for CV events were almost as high as the initial hospitalization costs, but much higher for 2- and 3-year follow-up.</p

Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure