Stabilization of partially folded states in protein folding/misfolding transitions by hydrostatic pressure

In the last few years, hydrostatic pressure has been extensively used in the study of both protein folding and misfolding/aggregation. Compared to other chemical or physical denaturing agents, a unique feature of pressure is its ability to induce subtle changes in protein conformation, which allow the stabilization of partially folded intermediate states that are usually not significantly populated under more drastic conditions (e.g., in the presence of chemical denaturants or at high temperatures). Much of the recent research in the field of protein folding has focused on the characterization of folding intermediates since these species appear to be involved in a variety of disease-causing protein misfolding and aggregation events. The exact mechanisms of these biologicalphenomena, however, are still poorly understood. Here, we review recent examples of the use of hydrostatic pressure as a tool to obtain insight into the forces and energetics governing the productive folding or the misfolding and aggregation of proteins.

A morphometric study of the lumbar spinous process in the Chinese population

Our goal was to analyze the anatomical parameters of the lumbar spine spinous process for an interspinous stabilization device designed for the Chinese population and to offer an anatomical basis for its clinical application. The posterior lumbar spines (T12-S1) of 52 adult cadavers were used for measuring the following: distance between two adjacent spinous processes (DB), distance across two adjacent spinous processes (DA), thickness of the central spinous processes (TC), thickness of the superior margin of the spinous processes (TS), thickness of the inferior margin of the spinous processes (TI), and height of the spinous processes (H). Variance and correlation analyses were conducted for these data, and the data met the normal distribution and homogeneity of variance. DB decreased gradually from L1-2 to L5-S1. DA increased from T12-L1 to L2-3 and then decreased from L2-3 to L4-5. The largest H in males was noted at L3 (25.45±5.96 mm), whereas for females the largest H was noted at L4 (18.71±4.50 mm). Usually, TS of the adjacent spinous process was lower than TI. Based on the anatomical parameters of the lumbar spinous processes obtained in this study, an “H”-shaped coronal plane (posterior view) was proposed as an interspinous stabilization device for the Chinese population. This study reports morphometric data of the lumbar spinous processes in the Chinese population, which provides an anatomical basis for future clinical applications.

Optimizing counterparty credit risk portfolio by reducing exposure at default variance

Rahoitusyhtiöt pitävät omaa pääomaa taseessa harvinaisen suuria markkinamuutoksia varten ja tämän pääoman määrä on ohjattu valvontaviranomaisten toimesta. Euroopassa Basel akordi antaa suuntaviivat näille säädöksille. 2007 vuoden finanssikriisin jälkeen rahoitusyhtiöt sekä valvojat ovat olleet entistä kiinnostuneempia pääoman riittävyydestä. Tutkimuksia riskistä, säädöksistä ja pääomavaateen madaltamisesta on tehty aikaisemmin, mutta tässä tutkimuksessa keskitytään vaateen jatkuvan muutoksen suuruuteen. Tutkimus sisältää hypoteettisen vastapuoliriski portfolion, jossa on mukana valuuttajohdannaisia. Tätä portfoliota simuloidaan eri tavoin, jotta nähtäisiin kuinka suuri vaikutus portfolion koostumuksella voi olla pääomavaateen varianssiin. Jos tämä muuttuja on merkittävä, pitäisikö rahoitusyhtiöiden yrittää pienentää muutosta, jotta yhtiöiden varapääoman määrää voitaisiin alentaa? Tutkimuksessa on myös haastateltu Suomen johtavia vastapuoliriski asiantuntijoita, jotta nähtäisiin rahoitusalan oma näkemys asian merkittävyydestä. Tutkimusmenetelminä toimivat haastattelut sekä numeerinen analyysi hypoteettisella portfoliolla. Kaupat tähän vastapuoliriski portfolioon on luotu 14 vuoden ajalle ja se sisältää ainoastaan valuuttajohdannaisia viidessä eri valuutassa. Riski lasketaan markkina-arvo menetelmällä, joista lasketaan VaR-mallilla tulevaisuuden riski nettoutuksen kera. Portfolion rakennetta muutetaan simuloinneissa, jotta nähtäisiin vaikutus tulevaisuuden riskeille, joita käytetään edustamaan pääomavaateen määrää ja sen vaihtelua yli ajan. Portfolioiden riskejä lasketaan myös rasituskokeiden avulla, jotta tuloksista saataisiin mahdollisimman todenmukaisia. Analyyttinen osuus tutkimuksesta näyttää sen, että tämän kaltainen optimointi on suuresti riippuvainen alkuperäisestä portfoliosta, jonka määrittää yleisesti rahoitusyhtiön myyntistrategia. Yleisesti ottaen pääomavaateen varianssin muutos voi simuloinneissa olla melko suurta, varsinkin jos mukaan huomioidaan rasitus testit, puuttuvat tuotteet sekä muut pääomavaateen laskentaan huomioitavat seikat. Haastatteluissa saatiin selville millainen optimointi voisi olla mahdollista todellisuudessa. Huomattiin myös että tämän kaltainen ajattelumalli on jo huomattu alalla ennestään. Jon Gregory jopa mainitsi, että jotkin rahoitusyhtiöt ovat enemmän kiinnostuneita muutosten pienentämisestä kuin itse pääomavaateen suuruudesta. Näyttääkin siltä, että tämän aihepiiri vaatisi entistä enemmän tutkimusta, sillä sitä ei ennestään vielä ole, ja rahoitusyhtiöt ovat jo alkaneet etsimään uusia keinoja selvitäkseen rahoitusalalla, joka on yhä entisestään kilpailullisempi.

Variance reduction properties of dynamic hedging models - empirical evidence from BRICS countries

This Master’s Thesis analyses the effectiveness of different hedging models on BRICS (Brazil, Russia, India, China, and South Africa) countries. Hedging performance is examined by comparing two different dynamic hedging models to conventional OLS regression based model. The dynamic hedging models being employed are Constant Conditional Correlation (CCC) GARCH(1,1) and Dynamic Conditional Correlation (DCC) GARCH(1,1) with Student’s t-distribution. In order to capture the period of both Great Moderation and the latest financial crisis, the sample period extends from 2003 to 2014. To determine whether dynamic models outperform the conventional one, the reduction of portfolio variance for in-sample data with contemporaneous hedge ratios is first determined and then the holding period of the portfolios is extended to one and two days. In addition, the accuracy of hedge ratio forecasts is examined on the basis of out-of-sample variance reduction. The results are mixed and suggest that dynamic hedging models may not provide enough benefits to justify harder estimation and daily portfolio adjustment. In this sense, the results are consistent with the existing literature.

Optimization of the valence energy variance of the CuH molecule

We developed the concept of split-'t to deal with the large molecules (in terms of the number of electrons and nuclear charge Z). This naturally leads to partitioning the local energy into components due to each electron shell. The minimization of the variation of the valence shell local energy is used to optimize a simple two parameter CuH wave function. Molecular properties (spectroscopic constants and the dipole moment) are calculated for the optimized and nearly optimized wave functions using the Variational Quantum Monte Carlo method. Our best results are comparable to those from the single and double configuration interaction (SDCI) method.

Heterodox Inflation Stabilization in Argentina, Brazil, and Israel. A Historical Review and Some Stylized Facts

This article presents a review of the stabilization attempts in Argentina, Brazil, and Israel during the 1980’s. Earlier research is summarized and complemented with additional sources of contemporaneous information and a detailed analysis of institutional features. The examination of these episodes underscores the strong economic and empirical relationship between the governments’ fiscal policy and the rate of inflation.

Credibility and Signaling in Disinflation- a Cross Country Examination

This paper develops a model of money demand where the opportunity cost of holding money is subject to regime changes. The regimes are fully characterized by the mean and variance of inflation and are assumed to be the result of alternative government policies. Agents are unable to directly observe whether government actions are indeed consistent with the inflation rate targeted as part of a stabilization program but can construct probability inferences on the basis of available observations of inflation and money growth. Government announcements are assumed to provide agents with additional, possibly truthful information regarding the regime. This specification is estimated and tested using data from the Israeli and Argentine high inflation periods. Results indicate the successful stabilization program implemented in Israel in July 1985 was more credible than either the earlier Israeli attempt in November 1984 or the Argentine programs. Government’s signaling might substantially simplify the inference problem and increase the speed of learning on the part of the agents. However, under certain conditions, it might increase the volatility of inflation. After the introduction of an inflation stabilization plan, the welfare gains from a temporary increase in real balances might be high enough to induce agents to raise their real balances in the short-term, even if they are uncertain about the nature of government policy and the eventual outcome of the stabilization attempt. Statistically, the model restrictions cannot be rejected at the 1% significance level.

Testing Mean-Variance Efficiency in CAPM with Possibly Non-Gaussian Errors : An Exact Simulation-Based Approach

In this paper we propose exact likelihood-based mean-variance efficiency tests of the market portfolio in the context of Capital Asset Pricing Model (CAPM), allowing for a wide class of error distributions which include normality as a special case. These tests are developed in the frame-work of multivariate linear regressions (MLR). It is well known however that despite their simple statistical structure, standard asymptotically justified MLR-based tests are unreliable. In financial econometrics, exact tests have been proposed for a few specific hypotheses [Jobson and Korkie (Journal of Financial Economics, 1982), MacKinlay (Journal of Financial Economics, 1987), Gib-bons, Ross and Shanken (Econometrica, 1989), Zhou (Journal of Finance 1993)], most of which depend on normality. For the gaussian model, our tests correspond to Gibbons, Ross and Shanken’s mean-variance efficiency tests. In non-gaussian contexts, we reconsider mean-variance efficiency tests allowing for multivariate Student-t and gaussian mixture errors. Our framework allows to cast more evidence on whether the normality assumption is too restrictive when testing the CAPM. We also propose exact multivariate diagnostic checks (including tests for multivariate GARCH and mul-tivariate generalization of the well known variance ratio tests) and goodness of fit tests as well as a set estimate for the intervening nuisance parameters. Our results [over five-year subperiods] show the following: (i) multivariate normality is rejected in most subperiods, (ii) residual checks reveal no significant departures from the multivariate i.i.d. assumption, and (iii) mean-variance efficiency tests of the market portfolio is not rejected as frequently once it is allowed for the possibility of non-normal errors.

The Wild Bootstrap for the Variance Radio Test.

Rapport de recherche

The role of financial markets in the stabilization and reconstruction of Lebanon.

Rapport de recherche