Terms Of Affinity Research Articles

Substrate-assisted activation and selectivity of the bacterial RavD effector deubiquitinylase.

Deubiquitinylases (DUBs) catalyze the peptide bond cleavage of specific ubiquitin linkages at distinct protein substrates. Pathogens from viruses and bacteria independently developed effector proteins with DUB activity to mimic host DUB functions and circumvent immune responses. The effector protein RavD from Legionella pneumophila cleaves linear ubiquitin chains with an exclusive methionine-1 selectivity. It thus performs as a functional analogue of the human DUB OTULIN, which achieves its selectivity only via a specialized proximal ubiquitin S1' binding site as well as a substrate-assisted activation of the catalytic triad. An analysis of the crystal structures of bacterial RavD in its free and di-ubiquitin-bound forms, in order to rationalize the structural basis for its selectivity and activation mechanism, is not fully conclusive. As these ambiguities might arise from the introduced double mutation of the di-ubiquitin substrate in the RavD-di-ubiquitin complex crystal structure, biomolecular modeling, and molecular dynamics sampling (1-2μs for each system of RavD and OTULIN) were employed to reconstitute the physiological RavD-di-ubiquitin complex. The simulations show that the distal S1 ubiquitin binding sites of RavD and OTULIN are similar in terms of interface area, composition, and ubiquitin binding affinity. The proximal S1' site of RavD, in contrast, is significantly smaller and ubiquitin binding is weaker and more flexible than in OTULIN. Upon substrate access, the residues of the catalytic triad of RavD show a reduction of flexibility and a conformational transition toward a catalytically active state. Thus, the enzymatic activation of RavD is presumably also substrate-assisted and a clear rationale for the common M1-substrate selectivity.

Raman Molecular Fingerprints of SARS-CoV-2 British Variant and the Concept of Raman Barcode.

The multiple mutations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus have created variants with structural differences in both their spike and nucleocapsid proteins. While the functional relevance of these mutations is under continuous scrutiny, current findings have documented their detrimental impact in terms of affinity with host receptors, antibody resistance, and diagnostic sensitivity. Raman spectra collected on two British variant sub‐types found in Japan (QK002 and QHN001) are compared with that of the original Japanese isolate (JPN/TY/WK‐521), and found bold vibrational differences. These included: i) fractions of sulfur‐containing amino acid rotamers, ii) hydrophobic interactions of tyrosine phenol ring, iii) apparent fractions of RNA purines and pyrimidines, and iv) protein secondary structures. Building upon molecular scale results and their statistical validations, the authors propose to represent virus variants with a barcode specially tailored on Raman spectrum. Raman spectroscopy enables fast identification of virus variants, while the Raman barcode facilitates electronic recordkeeping and translates molecular characteristics into information rapidly accessible by users.

Imaging of Glioblastoma Tumor-Associated Myeloid Cells Using Nanobodies Targeting Signal Regulatory Protein Alpha

Glioblastoma (GBM) is the most common malignant primary brain tumor. Glioblastomas contain a large non-cancerous stromal compartment including various populations of tumor-associated macrophages and other myeloid cells, of which the presence was documented to correlate with malignancy and reduced survival. Via single-cell RNA sequencing of human GBM samples, only very low expression of PD-1, PD-L1 or PD-L2 could be detected, whereas the tumor micro-environment featured a marked expression of signal regulatory protein alpha (SIRPα), an inhibitory receptor present on myeloid cells, as well as its widely distributed counter-receptor CD47. CITE-Seq revealed that both SIRPα RNA and protein are prominently expressed on various populations of myeloid cells in GBM tumors, including both microglia- and monocyte-derived tumor-associated macrophages (TAMs). Similar findings were obtained in the mouse orthotopic GL261 GBM model, indicating that SIRPα is a potential target on GBM TAMs in mouse and human. A set of nanobodies, single-domain antibody fragments derived from camelid heavy chain-only antibodies, was generated against recombinant SIRPα and characterized in terms of affinity for the recombinant antigen and binding specificity on cells. Three selected nanobodies binding to mouse SIRPα were radiolabeled with 99mTc, injected in GL261 tumor-bearing mice and their biodistribution was evaluated using SPECT/CT imaging and radioactivity detection in dissected organs. Among these, Nb15 showed clear accumulation in peripheral organs such as spleen and liver, as well as a clear tumor uptake in comparison to a control non-targeting nanobody. A bivalent construct of Nb15 exhibited an increased accumulation in highly vascularized organs that express the target, such as spleen and liver, as compared to the monovalent format. However, penetration into the GL261 brain tumor fell back to levels detected with a non-targeting control nanobody. These results highlight the tumor penetration advantages of the small monovalent nanobody format and provide a qualitative proof-of-concept for using SIRPα-targeting nanobodies to noninvasively image myeloid cells in intracranial GBM tumors with high signal-to-noise ratios, even without blood-brain barrier permeabilization.

The Effect of Brand Image, Product Prices, and Product Quality on Repurchases of Kopi Petani Nusantara (Case Study on Kopi Petani Nusantara Consumers in Jakarta)

The high interest in coffee consumption in Indonesia is not only a coffee-producing country, as quite a lot of consumers. Indonesia was ranked 4th as the world's largest coffee producer in 2016 after Brazil, Vietnam, and Colombia. Of the many types of coffee, in general, there are two types of coffee marketed in Indonesia, namely Arabica coffee and Robusta coffee. This research was conducted using quantitative methods with a population and sample of 112 respondents. The data analysis method used is binomial logistic regression analysis. The results showed that the quality of brand image, product price, and product quality are factors that determine repurchase decisions on Kopi Petani Nusantara in the archipelago, which shows 57.1% to be the determining factor while the rest is determined by other factors. This happens because of the better brand image of a product, so buyers will make repeat purchases to meet their needs, both in terms of Recognition, Reputation, Affinity, and Domain.

The Deglycosylated Form of 1E12, a Monoclonal Anti-PF4 IgG, Strongly Inhibits Antibody-Triggered Cellular Activation in Vaccine-Induced Thrombotic Thrombocytopenia, and Is a Potential New Treatment for Vιττ

▪IntroductionVaccine-induced thrombotic thrombocytopenia (VITT) is a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, likely due to anti-platelet factor 4 (PF4) IgG antibodies. The specificity and platelet-activating activity of VITT antibodies strikingly resemble that of antibodies detected in “autoimmune” heparin-induced thrombocytopenia (HIT), but their features remain poorly characterized. In particular, a better knowledge of these antibodies should help to understand the mechanisms leading to hypercoagulability and the particular thrombotic events observed in VITT, but rarely in typical HIT. We have recently developed a chimeric IgG1 anti-PF4 antibody, 1E12, which strongly mimics “autoimmune” HIT antibodies in terms of specificity and cellular effects. Therefore, we assessed whether 1E12 could mimic VITT antibodies. We then evaluated the capability of DG-1E12, a deglycosylated form of 1E12 unable to bind FcγR, to inhibit cellular activation induced by VITT antibodies.Methods and ResultsUsing a PF4-sensitized serotonin release assay (PF4-SRA) (Vayne C, New Engl J Med, 2021), we demonstrated that 1E12 (5 and 10 μg/mL) strongly activated platelets, with a pattern similar to that obtained with human VITT samples (n=7), i.e. in a PF4-dependent manner and without heparin. This platelet activation was inhibited by low heparin concentration (0.5 IU/mL), an effect also observed with VITT samples. Serotonin release induced by 1E12 was also fully inhibited by IV-3, a monoclonal antibody blocking FcγRIIa, or by IdeS, a bacterial protease that cleaves IgG and strongly inhibits the binding of IgG antibodies to FcγRIIa. This inhibitory effect of IV-3 and IdeS strongly supports that interactions between pathogenic anti-PF4 IgG and FcγRIIa play a central role in VITT.Incubation of 1E12 or VITT samples with isolated neutrophils (PMN) and platelets with PF4 (10 µg/mL) strongly induced DNA release and NETosis, supporting that PMN are involved in the processes leading to thrombosis in VITT. Furthermore, when whole blood from healthy donors incubated with 1E12 or VITT plasma was perfused in capillaries coated with von Willebrand Factor, numerous large platelet/leukocyte aggregates containing fibrin(ogen) were formed.To investigate whether 1E12 and VITT antibodies recognize overlapping epitopes on PF4, we then performed competitive assays with a deglycosylated form of 1E12 (DG-1E12), still able to bind PF4 but not to interact with Fcγ receptors. In PF4-SRA, pre-incubation of DG-1E12 (50 µg/mL) dramatically reduced platelet activation induced by VITT antibodies, which was fully abrogated for 9 of the 14 VITT samples tested. Additional experiments using a whole blood PF4-enhanced flow cytometry assay recently designed for VITT diagnosis (Handtke et al, Blood 2021), confirmed that DG-1E12 fully prevented platelet activation induced by VITT antibodies. Moreover, when platelets and neutrophils were pre-incubated with DG-1E12 (100 µg/mL), NETosis and thus DNA release, nuclear rounding, and DNA decondensation induced by VITT antibodies were completely inhibited. Finally, DG-1E12 (100 µg/mL) also fully abolished VITT antibody-mediated thrombus formation in whole blood in vitro under vein flow conditions. Comparatively, DG-1E12 did not inhibit ALB6, a murine monoclonal anti-CD9 antibody, which also strongly activates platelets in a FcγRIIa-dependent manner.ConclusionsOur results show that 1E12 exhibits features similar to those of human VITT antibodies in terms of specificity, affinity and cellular effects, and could therefore be used as a model antibody to study the pathophysiology of VITT. Our data also demonstrate that DG-1E12 prevents blood cell activation and thrombus formation induced by VITT antibodies, likely due to the competitive effect of its Fab fragment on antibody binding to PF4. DG-1E12 may allow the development of a new drug neutralizing the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT. DisclosuresThiele: Bristol Myers Squibb: Honoraria, Other; Pfizer: Honoraria, Other; Bayer: Honoraria; Chugai Pharma: Honoraria, Other; Novo Nordisk: Other; Novartis: Honoraria; Daichii Sankyo: Other. Pouplard: Stago: Research Funding. Greinacher: Macopharma: Honoraria; Biomarin/Prosensa: Other, Research Funding; Sagent: Other, Research Funding; Rovi: Other, Research Funding; Gore inc.: Other, Research Funding; Bayer Healthcare: Other, Research Funding; Paringenix: Other, Research Funding; BMS: Honoraria, Other, Research Funding; MSD: Honoraria, Other, Research Funding; Boehringer Ingelheim: Honoraria, Other, Research Funding; Aspen: Honoraria, Other, Research Funding; Portola: Other; Ergomed: Other; Instrument Laboratory: Honoraria; Chromatec: Honoraria. Gruel: Stago: Other: symposium fees, Research Funding. Rollin: Stago: Research Funding.

Bond risk premia in emerging markets: evidence from Brazil, China, Mexico, and Russia

ABSTRACT We employ an affine term structure model with no-arbitrage restrictions and unspanned risk factors to analyse the global and domestic determinants of bond risk premia in four major emerging markets (Brazil, China, Mexico, and Russia). Among the risk factors, we select national inflation and economic growth, and the country-specific nominal exchange rate against the US dollar as the variables related to the domestic economy. We include a measure of worldwide economic activity, the Market Volatility Index (VIX), and an aggregate price index of commodities in the group of global factors. Our model captures (long-term) movements of realized risk premia and indicates that global economic and financial factors play a relevant role in explaining country-specific bond risk premia dynamics. In contrast, domestic variables carry little explanatory power to rationalize risk premia developments in these four economies. We also provide evidence of heterogeneous responses of country-specific risk premia to global and domestic shocks.

Polymeric Network of Amines and Metals Colloids: Conformational Analysis of Interaction, Orientation with DNA

Over the last decade numerous promising synthetic, non-viral gene delivery systems have been developed and an outline of their potential advantages and disadvantages has materialized [1]. Synthetic vectors have advantages in interconnected pharmaceutical issues, safety, and ease of use but tend to be less efficient than some viral systems. Advanced delivery systems can be developed that will have higher potential and more advantages. Moreover, physicochemical properties including charge, dissociation behavior, and the shape and nanoparticle size of the cationic complexes can play a significant role in efficient gene transfer in vitro and in vivo. Even though the interaction between the polymeric cations and DNA is electrostatic in origin, geometric and chemical structures of the polymer also play a substantial character in complex formation. Even the number of positive charges and the spacing of cationic charges within the polymer upsets the size of DNA nanoparticles fashioned by polycations [2]. Hence, a complete set of biophysical measurements for the characterization of physical and chemical properties of cationic complexes offered consists of cationic polymers/surfactants with DNA. By considering this beginning as a study on the structural properties of the cationic complexes, the understanding of the effect of polymer architecture on the DNA/cationic polymer interaction at the molecular level in terms of DNA stability, conformation, size, shape, binding affinity, and complete thermodynamics of the interaction are also necessarily required [3].

Arbitrage-free Nelson\u2013Siegel model for multiple yield curves

We propose an affine term structure model that allows for tenor-dependence of yield curves and thus for different risk categories in interbank rates, an important feature of post-crisis interest rate markets. The model has a Nelson–Siegel factor loading structure and thus economically well interpretable parameters. We show that the model is tractable in terms of estimation and provides good in-sample fit and out-of-sample forecasting performance. The proposed model is arbitrage-free across maturities and tenors, and thus perfectly suited for risk management and pricing purposes. We apply our framework to the pricing of caplets in order to illustrate its practical applicability and its suitability for stress testing.

WaterMap and Molecular Dynamic Simulation-Guided Discovery of Potential PAK1 Inhibitors Using Repurposing Approaches.

p21-Activated kinase 1 (PAK1) is positioned at the nexus of several oncogenic signaling pathways. Currently, there are no approved inhibitors for disabling the transfer of phosphate in the active site directly, as they are limited by lower affinity, and poor kinase selectivity. In this work, a repurposing study utilizing FDA-approved drugs from the DrugBank database was pursued with an initial selection of 27 molecules out of ∼2162 drug molecules, based on their docking energies and molecular interaction patterns. From the molecules that were considered for WaterMap analysis, seven molecules, namely, Mitoxantrone, Labetalol, Acalabrutinib, Sacubitril, Flubendazole, Trazodone, and Niraparib, ascertained the ability to overlap with high-energy hydration sites. Considering many other displaced unfavorable water molecules, only Acalabrutinib, Flubendazole, and Trazodone molecules highlighted their prominence in terms of binding affinity gains through ΔΔG that ranges between 6.44 and 2.59 kcal/mol. Even if Mitoxantrone exhibited the highest docking score and greater interaction strength, it did not comply with the WaterMap and molecular dynamics simulation results. Moreover, detailed MD simulation trajectory analyses suggested that the drug molecules Flubendazole, Niraparib, and Acalabrutinib were highly stable, observed from their RMSD values and consistent interaction pattern with Glu315, Glu345, Leu347, and Asp407 including the hydrophobic interactions maintained in the three replicates. However, the drug molecule Trazodone displayed a loss of crucial interaction with Leu347, which was essential to inhibit the kinase activity of PAK1. The molecular orbital and electrostatic potential analyses elucidated the reactivity and strong complementarity potentials of the drug molecules in the binding pocket of PAK1. Therefore, the CADD-based reposition efforts, reported in this work, helped in the successful identification of new PAK1 inhibitors that requires further investigation by in vitro analysis.

Almost Output Regulation of Switched Affine Systems and Its Application to a Circuit Model

This brief is concerned with the almost output regulation issue of switched affine systems. For switched affine systems, affine terms make the absence of the common equilibrium point, which also brings the distinct and difficulty on the analysis of output regulation performance. Moreover, in contract to the classical output regulation problem, a more extensive situation where the controlled plant and exosystem suffer from the unknown external interferences is concerned. Accordingly, the concept of the almost output regulation problem of switched affine systems is presented. Then, the co-design method of the switching law and regulators is established to guarantee the almost output regulation property. The given co-design method gets ride of the requirement for the almost output regulation performance of each subsystem. At last, the employed electronic circuit model substantiates the applicability and validity of the developed results.

Solvent affinity and its applications in the prediction of mutual solubility

The solvent affinity may be defined as the degree of similarity between solute and solvent molecules in terms of the solute–solvent interactions at infinite dilution, which comprises contributions from resemblance in molecular structure (size and energy) Se and resemblance in Hansen solubility parameter (HSP) Sh. The physical meaning of Sh may be the ratio of mixing deriving force to mixing resisting force. A theoretical concept and estimation method of hydrophile-lipophile balance (HLB) for surfactants (emulsifiers) defined in terms of solvent affinity was proposed in this work. Its applications in the prediction of liquid organic − water mutual solubility, solubility of solid solutes in pure solvents and HLB values of surfactants have been examined extensively with successful results.

Tuning the Activity of a Hybrid Polymer-Oxocluster Catalyst: A Composition-Selectivity Correlation.

Zr-based oxoclusters MxOy(OR)w(OOR’)z are promising catalysts for the activation of hydrogen peroxide. However, they need to be integrated into suitable matrices to increase their hydrolytic stability and allow for their recovery after use. Polymeric materials can be successfully employed for this aim, since they modify the properties of the resulting hybrid materials, in terms of polarity and chemical affinity for the substrates, improving the catalytic activity. Herein, we report the synthesis of different acrylic polymers based on various co-monomers (methyl methacrylate (MMA), 2,2,2-trifluoroethylmethacrylate (TFMA) and 3-methacryloxypropyltrimethoxylsilane (MAPTMS)) covalently cross-linked by a Zr4-based oxocluster, whose composition was tuned to optimise the catalytic oxidation of methyl p-tolyl sulphide. To assess their properties and stability, the materials were characterised via Fourier Transform Infrared (FT-IR) and Raman spectroscopies, Thermogravimetric Analysis (TGA), Solid-State NMR (SS-NMR) and X-Ray Absorption Spectroscopies XAS, before and after catalytic turnover.

Long-term foreign exchange risk premia and inflation risk

As highlighted by recent literature, long-term foreign exchange risk premia (FRP) of a currency pair tend to covary negatively with short-term real interest rate differentials (RIRD) of the pair. We fit an affine term structure model for 9 major currencies against the US dollar and estimate two components of this covariance: the real risk premia (RRP) component and the inflation risk premia differential (IRPD) component. We find that the IRPD component is significantly negative for all currency pairs in our sample. We propose a macro-finance model to understand the types of shocks that generate such covariance.

In-silico Inhibitory Potential of Triphala Constituents Against Cytochrome P450 2E1 for the Prevention of Thioacetamide-induced Hepatotoxicity

Background: Triphala, which is a combination of fruits of Terminalia chebula, Terminalia bellerica and Embilica officinalis generally recommended as herbal drug formulation in the Indian traditional medicine system.
 Study Design: To study the in-silico inhibitory potential of Triphala constituents against cytochrome P450 2E1 (CYP2E1) for the prevention of Thioacetamide-induced Hepatotoxicity
 Place and Duration of Study: The work has been performed at MUP's College of Pharmacy (B Pharm), Degaon, Risod, Washim, Maharashtra, India in between February 2021 to May 2021.
 Methodology: We have studied the inhibitory potential of Triphala on CYP2E1 by applying molecular docking tools. The major chemical constituents of Triphala i.e. gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid were docked on CYP2E1.
 Results: Docking results revealed the very good inhibitory potential of Triphala in terms of binding affinity towards CYP2E1. All the chemical constituents have formed at least 2 and at most 6 hydrogen bonds with the crystal structure of CYP2E1. The binding energies (kcal/mol) of gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid are -6.1, -7.1, -9.1, -8.3, -6.3, and -5.7, respectively. Ellagic acid has formed strong hydrogen bonds with Thr-303 and Thr-304 with bond length of 1.98 A0 and 2.26 A0 which confirms the excellent inhibition of CYP2E1.
 Conclusion: These findings can be used to control the CYP2E1-facilitated biotransformation and drug interactions in the development of new chemical entities. In future, these phytoconstituents can be used as lead molecules to overcome the cancer associated with oxidative stress resulting from the hyperactivity of CYP2E1.

Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin.

There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure-activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (Kd determined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H-bonding interactions that modulate the potency of solithromycin analogs.

Exploring novel and potent molecules for disrupting DEPTOR-mTOR interaction through structure-steered screening, extra-exactitude molecular docking, prime binding free energy estimation and voguish molecular dynamics

Dep domain containing mTOR interacting protein (DEPTOR) has critical implications in the development and progression of human malignancies. Increased expression of DEPTOR promotes the growth of tumor cells by inhibiting the mTORC1, which alleviates the negative feedback inhibition by mTORC1 downstream target S6Ks on PI3K/AKT pathway thereby promotes cell survival and prevents apoptosis. This clearly suggests that targetting DEPTOR-mTOR interactions through small molecules may prove as an effective strategy for circumventing distinct cancers. In this study, we employed a top-down approach for finding three novel molecules which may prove effective in disrupting Deptor–mTOR interaction. Following DEPTOR modelling and validation we performed grid-directed structure-based screening by specifying the residues of DEPTOR known to interact with mTOR. A library of 10,000 protein–protein disrupting molecules was screened against the defined region of DEPTOR. From the screened molecules, 30 molecules with highest binding affinity were chosen for molecular docking. Thirty (30) extra-precision molecular docking experiments and 30 molecular mechanics generalized born surface area (MMGBSA) assays were performed. Following this top 10 molecules in terms of binding affinity were selected and the interaction profile of their corresponding docked files was generated. The top three molecules were finally selected after taking all the three parameters including docking score, binding energy value and interaction profile into consideration. For atomistic insights regarding DEPTOR-topmost hit interactions, molecular dynamics was performed for 100 ns. This molecule after further evaluation may prove as promising candidate for anticancer therapy. Communicated by Ramaswamy H. Sarma

Observer-based fault estimation for a class of discrete-time switched affine systems: An application to the DC-DC converter

This paper studies the observer-based fault estimation for a class of discrete-time switched affine systems. A new class of fault estimator with an affine term is first established based on the state observer approach, and a target solution problem of the augmented error system is established under the H∞ performance scheme. The min-type Lyapunov function and its associated switching function are used to obtain the stability condition of the augmented error system in terms of Lyapunov-Metzler inequality. The idea of minimizing the volume of the ellipsoid is adopted containing the set of attraction in order to obtain an attraction set as small as possible. Through solving an optimization problem, the stability of augmented error system can be ensured, and the corresponding fault estimator design is realized in the form of linear matrix inequalities. Finally, a practical application of three level DC-DC multicellular converter is illustrated to verify the effectiveness and practicability of the developed observer-based fault estimation approach.

Highly Conductive Nanocrystalline Diamond Films and Electronic Metallization Scheme.

By using a methane and hydrogen process gas mixture in an appropriate hot-filament CVD process without further dopant, high electrical conductivity of over 100 S/cm has been achieved in nanocrystalline diamond films deposited on silicon single-crystalline substrates. Furthermore, it was found that an oxygen reactive-ion etching process (O-RIE) can improve the diamond film surface’s electron affinity, thus reducing the specific contact resistance. The reduction of the specific contact resistance by a factor of up to 16 was realized by the oxygen ion etching process, down to . We provide a qualitative explanation for the mechanism behind the contact resistance reduction in terms of the electron affinity of the diamond surface. With the aid of XPS, AFM, and surface wetting measurements, we confirmed that a higher surface electron affinity is responsible for the lower specific contact resistance of the oxygen-terminated nanocrystalline diamond films.

Monetary policy surprises and their transmission through term premia and expected interest rates

Monetary policy moves the yield curve. What is the economic interpretation of such moves and what are their macroeconomic consequences? Applying an affine term structure model to high-frequency yield curve movements around FOMC announcements, we shed new light on these questions. Estimation is subject to restrictions addressing estimation bias in previous studies. By imposing additional structure, expectations and term premia are decomposed into three components interpreted as monetary policy action, expected path and its uncertainty. In a local projections model, the shocks identified by the three components provide insights into monetary policy transmission in the context of existing theories.

A Computational Analysis of the Tradeoff in the Estimation of Different State Space Specifications of Continuous Time Affine Term Structure Models

A Computational Analysis of the Tradeoff in the Estimation of Different State Space Specifications of Continuous Time Affine Term Structure Models