A Note on Business Cycle Accounting

Chari, Kehoe and McGrattan (2007) (CKM) show that a large class of dynamic stochastic general equilibrium (DSGE) models with various frictions and shocks is observationally equivalent to a benchmark real business cycle (RBC) model with correlated "wedges" in the RBC model's first-order conditions. The wedges in the static first-order conditions of the RBC model can be readily computed by evaluating the first-order conditions at the data and then solving for the wedges. In contrast, identification of the "investment wedge" in the RBC model's dynamic Euler equation requires the researcher to make assumptions about the expectation formation by agents in the RBC model. In particular, CKM assume that expectations are formed as if, from the perspective of the model's agents, wedges followed a vector autoregressive process of order one (VAR(1)). We show that wedges generally do not have a VAR(1) representation, implying that CKM's procedure is based on model-inconsistent expectations. We also provide an alternative, model-consistent approach to modeling expectation formation. On the former issue, we present a necessary and sufficient ``rank condition'' under which a detailed economy can be mapped into a benchmark model where wedges follow a VAR(1) process. On the latter issue, we suggest that the information set underlying the expectation formation should not only contain current wedges, but also all predetermined variables.Business Cycle Accounting; Model Consistent Expectations

Global Stationary Phase and the Sign Problem

We present a computational strategy for reducing the sign problem in the evaluation of high dimensional integrals with non-positive definite weights. The method involves stochastic sampling with a positive semidefinite weight that is adaptively and optimally determined during the course of a simulation. The optimal criterion, which follows from a variational principle for analytic actions S(z), is a global stationary phase condition that the average gradient of the phase Im(S) along the sampling path vanishes. Numerical results are presented from simulations of a model adapted from statistical field theories of classical fluids.Comment: 9 pages, 3 figures, submitted for publicatio

Effective Soft-Core Potentials and Mesoscopic Simulations of Binary Polymer Mixtures

Mesoscopic molecular dynamics simulations are used to determine the large scale structure of several binary polymer mixtures of various chemical architecture, concentration, and thermodynamic conditions. By implementing an analytical formalism, which is based on the solution to the Ornstein-Zernike equation, each polymer chain is mapped onto the level of a single soft colloid. From the appropriate closure relation, the effective, soft-core potential between coarse-grained units is obtained and used as input to our mesoscale simulations. The potential derived in this manner is analytical and explicitly parameter dependent, making it general and transferable to numerous systems of interest. From computer simulations performed under various thermodynamic conditions the structure of the polymer mixture, through pair correlation functions, is determined over the entire miscible region of the phase diagram. In the athermal regime mesoscale simulations exhibit quantitative agreement with united atom simulations. Furthermore, they also provide information at larger scales than can be attained by united atom simulations and in the thermal regime approaching the phase transition.Comment: 19 pages, 11 figures, 3 table

Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models

Copyright © 2022 The Authors. Published by American Chemical SocietyCombination therapies have emerged to mitigate Plasmodium drug resistance, which has hampered the fight against malaria. M5717 is a potent multistage antiplasmodial drug under clinical development, which inhibits parasite protein synthesis. The combination of M5717 with pyronaridine, an inhibitor of hemozoin formation, displays potent activity against blood stage Plasmodium infection. However, the impact of this therapy on liver infection by Plasmodium remains unknown. Here, we employed a recently described 3D culture-based hepatic infection platform to evaluate the activity of the M5717-pyronaridine combination against hepatic infection by P. berghei. This effect was further confirmed in vivo by employing the C57BL/6J rodent Plasmodium infection model. Collectively, our data demonstrate that pyronaridine potentiates the activity of M5717 against P. berghei hepatic development. These preclinical results contribute to the validation of pyronaridine as a suitable partner drug for M5717, supporting the clinical evaluation of this novel antiplasmodial combination therapy.This work was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). M.P. is a recipient of a “Concurso de Estímulo ao Emprego Científico” Principal Investigator award of Fundação para a Ciência e Tecnologia, Portugal (FCT), with ref. N. CEECIND/03539/2017. D.F. is funded by FCT project CRCNA/BRB/0281/2019. F.A. is recipient of a PhD fellowship PD/BD/128371/2017, funded by FCT.info:eu-repo/semantics/publishedVersio

A multiscale modeling study of loss processes in block-copolymer-based solar cell nanodevices

Flexible photovoltaic devices possess promising perspectives in opto-electronic technologies, where high mobility and/or large-scale applicability are important. However, their usefulness in such applications is currently still limited due to the low level of optimization of their performance and durability. For the improvement of these properties, a better understanding and control of small-scale annihilation phenomena involved in the photovoltaic process, such as exciton loss and charge carrier loss, is necessary, which typically implicates multiple length- and time-scales. Here, we study the causes for their occurrence on the example of nanostructured diblock- and triblock-copolymer systems by making use of a novel solar-cell simulation algorithm and explore new routes to optimize their photovoltaic properties. A particular focus is set on the investigation of exciton and charge carrier loss phenomena and their dependence on the inter-monomeric interaction strength, chain architecture, and external mechanical loading. Our simulation results reveal that in the regime from low up to intermediate χ-parameters an increasing number of continuous percolation paths is created. In this parameter range, the internal quantum efficiency (IQE) increases up to a maximum, characterized by a minimum in the number of charge losses due to charge recombination. In the regime of high χ-parameters both block-copolymer systems form nanostructures with a large number of bottlenecks and dead ends. These lead to a large number of charge losses due to charge recombination, charge trapping, and a deteriorated exciton dissociation, resulting in a significant drop in the IQE. Moreover, we find that the photovoltaic performance of the triblock-copolymer material decreases with increasing mechanical loading, caused by a growing number of charge losses due to charge recombination and charge accumulation. Finally, we demonstrate that the process of charge trapping in defects can be reversed by changing the polarity of the electrodes, which confers these materials the ability to be used as charge storage media

Microphase separation, stress relaxation and creep behavior of polyurethane nanocomposites

The microphase separation of polyurethane (PU) nanocomposite was studied. The result suggests that the addition of clay leads to a decrease in the size of hard domain and an increase in the degree of microphase separation. The stress relaxation and creep behavior of blank PU and PU/clay nanocomposites were investigated. The relaxation time spectrum and retardant time spectrum were derived according to the generalized Maxwell model and Voigt model with a Tikhonov regularization method. The characteristic relaxation time was identified with the corresponding relaxation process. At a small strain, the relaxation was mainly attributed to uncoiling/disentangling of soft segment chain network in the soft phase, with a single characteristic relaxation time in the range of 5~100s. The increase in the hard segment content leads to a decrease in the relaxation time, and the addition of clay leads to an increase in the relaxation time. At large strains, the multi-peak relaxations occurred, and they were attributed to the breakup of interconnected hard domains and pull-out of soft segment chains from hard domains, together with the disentangling of soft segment chain network in the soft phase. The creep results are in consistent with that of the stress relaxation. The relaxation and creep behavior were related to microphase separation of polyurethane. This study suggested that the relaxation spectrum H(ï´) can be used to examine the complicated relaxation processes for a multi-phase and multi-component polymer system

Ordered arrays of multiferroic epitaxial nanostructures

Epitaxial heterostructures combining ferroelectric (FE) and ferromagnetic (FiM) oxides are a possible route to explore coupling mechanisms between the two independent order parameters, polarization and magnetization of the component phases. We report on the fabrication and properties of arrays of hybrid epitaxial nanostructures of FiM NiFe2O4 (NFO) and FE PbZr0.52Ti0.48O3 or PbZr0.2Ti0.8O3, with large range order and lateral dimensions from 200 nm to 1 micron

Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients

The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma

Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future. © 2014 Adam et al

A new multiscale modeling method for simulating the loss processes in polymer solar cell nanodevices

The photoelectric power conversion efficiency of polymer solar cells is till now, compared to conventional inorganic solar cells, still relatively low with maximum values ranging from 7% to 8%. This essentially relates to the existence of exciton and charge carrier loss phenomena, reducing the performance of polymer solar cells significantly. In this paper we introduce a new computer simulation technique, which permits to explore the causes of the occurrence of such phenomena at the nanoscale and to design new photovoltaic materials with optimized opto-electronic properties. Our approach consists in coupling a mesoscopic field-theoretic method with a suitable dynamic Monte Carlo algorithm, to model the elementary photovoltaic processes. Using this algorithm, we investigate the influence of structural characteristics and different device conditions on the exciton generation and charge transport efficiencies in case of a novel nanostructured polymer blend. More specifically, we find that the disjunction of continuous percolation paths leads to the creation of dead ends, resulting in charge carrier losses through charge recombination. Moreover, we observe that defects are characterized by a low exciton dissociation efficiency due to a high charge accumulation, counteracting the charge generation process. From these observations, we conclude that both the charge carrier loss and the exciton loss phenomena lead to a dramatic decrease in the internal quantum efficiency. Finally, by analyzing the photovoltaic behavior of the nanostructures under different circuit conditions, we demonstrate that charge injection significantly determines the impact of the defects on the solar cell performance