bluuebunny/crossref_metadata_2025 huggingface dataset:
Hedging by Sequential Regression: an Introduction to the Mathematics of Option Trading
Authors: Föllmer H. , Schweizer M.
Published: July 2016

It is widely acknowledge that there has been a major breakthrough in the mathematical theory of option trading. This breakthrough, which is usually summarized by the Black–Scholes formula, has generated a lot of excitement and a certain mystique. On the mathematical side, it involves advanced probabilistic techniques from martingale theory and stochastic calculus which are accessible only to a small group of experts with a high degree of mathematical sophistication; hence the mystique. In its practical implications it offers exciting prospects. Its promise is that, by a suitable choice of a trading strategy, the risk involved in handling an option can be eliminated completely.

Since October 1987, the mood has become more sober. But there are also mathematical reasons which suggest that expectations should be lowered. This will be the main point of the present expository account. We argue that, typically, the risk involved in handling an option has an irreducible intrinsic part. This intrinsic risk may be much smaller than the a priori risk, but in general one should not expect it to vanish completely. In this more sober perspective, the mathematical technique behind the Black–Scholes formula does not lose any of its importance. In fact, it should be seen as a sequential regression scheme whose purpose is to reduce the a priori risk to its intrinsic core.

We begin with a short introduction to the Black–Scholes formula in terms of currency options. Then we develop a general regression scheme in discrete time, first in an elementary two-period model, and then in a multiperiod model which involves martingale considerations and sets the stage for extensions to continuous time. Our method is based on the interpretation and extension of the Black–Scholes formula in terms of martingale theory. This was initiated by Kreps and Harrison; see, e.g. the excellent survey of Harrison and Pliska (1981,1983). The idea of embedding the Black-Scholes approach into a sequential regression scheme goes back to joint work of the first author with D. Sondermann. In continuous time and under martingale assumptions, this was worked out in Schweizer (1984) and Föllmer and Sondermann (1986). Schweizer (1988) deals with these problems in a general semimartingale model.
The Random Walk of a Simple Risk Business
Authors: Seal H. L.
Published: July 2016

We suppose that a risk business issues a single type of contract under which, in return for a unit “premium”, it will pay a “sum insured”m(mbeing an integer) on the occurrence of a contingency of probabilityq˂ ½. The expected gain on each contract is i—mqand is assumed to be positive. This type of enterprise is conveniently denominated asimple risk business. Two “real life” situations it simulates are those of a group life policy for a uniform amount covering a number of young lives (e.g., university students), and a roulette casino where the stakes are uniform and the bets are limited to the single numbers o to 36.

The risk business is supposed to commence its operations with a “risk reserve” ofKunits. Each premium is added to this reserve as it is received and all claims by contract holders are paid there-from. We say that the business is “ruined” as soon as the risk reserve becomeszeroornegative(though it could be argued that it would be unethical to accept a premium once the risk reserve is less thanm— 1). On the other hand, if the reserve reaches an amountMunits no further premiums are paid into it until a claim occurs to reduce it belowM(de Finetti, 1957). The risk business intends to continue its operations for a long, but finite, period unless ruined in the meantime.

We consider two probabilities: (i) υx, the chance of eventual ruin given that the risk reserve is nowx, and (ii) υx, n, the probability that ruin occurs as a result of thenth contract (simultaneous contracts being ranked in a prearranged, e.g., alphabetical, order). Clearly

and we will write I — νx=μx
Experience Rating in Subsets of Risks
Authors: Bichsel Fritz
Published: July 2016

We consider a set of risks B, which is divided into subsets Bi according to some property as profession, region etc. The subsets Bi are thought to be too small to permit a calculation of a premium from their own experience. On the other hand we assume that there are differences between the Bi. This paper tries to give a solution to the problem how the experience of the single Bi should be combined with that of the whole B.

The problem is treated only with respect to frequencies of claims. The amounts of the claims are not taken into consideration. I suppose that an extension of the theory to amounts is possible and highly desirable for practical applications. Lack of time did not permit me however to proceed to such an extension in this paper.

I think that the methods developed in the sequel might be applied to the following practical problems:

— rate making

— experience rating in the restrictive sense of the word, i.e. adjusting periodically the premium or granting premium refunds according to the experience of every single Bi

— judging the experience of a. Bi.

I do not give a list of references which would have to be very long. The basic idea was, as far as I know, first developed by Lundberg.
On the solvency of insurance companies
Authors: Pentikäinen T.
Published: July 2016

This report is a contribution to the discussion on the solvency problem, which has been taking place at ASTIN-meetings. In his report in Edinburgh 1964 Beard referred to many aspects which are closely connected with the problem. Such aspects are

1. the evaluation of liabilities;

2. the evaluation of assets;

3. the level of the premiums of long term policies and

4. reinsurance.

If all of these are not in order, there is no sense in speaking about solvency. E.g. a solvency margin defined as the difference between assets and the expected value of liabilities would not be a reliable measure of the financial state of an insurance company, if either of these—or maybe both—are not evaluated in a reliable way. The fixing of solvency margins is not an isolated problem, on the contrary it is only part of the security measures which must all be managed at the same time. The ultimate purpose of the security system prescribed by legislation must be to safeguard policyholders and claimants against losses.
Credible Means are exact Bayesian for Exponential Families
Authors: Jewell William S.
Published: July 2016

The credibility formula used in casualty insurance experience rating is known to be exact for certain prior-likelihood distributions, and is the minimum least-squares unbiased estimator for all others. We show that credibility is, in fact, exact for all simple exponential families where the mean is the sufficient statistic, and is also exact in an extended sense for all regular distributions with their natural conjugate priors where there is a fixed-dimensional sufficient statistic.
The Mincing Machine Revisited
Authors: Bühlmann Hans
Published: July 2016

For the 4th ASTIN colloquium in Trieste (1963) Robert E. Beard [1] had initiated the topic of extreme value theory and its application to actuarial problems. The impetus came from Gumbel's book [2], published in 1958, and the idea of applying extreme value theory ran about as follows:

Problem: Given: The size of the largest claim observed = XN

The number of observed claims = N.

Find: The excess of loss premium for a portfolio of independent risks identical with those under observation.

The idea was to use Gnedenko's limit distribution for the wide class of distribution functions with an unlimited tail and finite moments, the “exponential type” in Gumbel's terminology, and to calculate the excess of loss premium on the basis of this limit distribution.

The discussion in Trieste was very lively and culminated in Jan Jung's citation of Jan Jung [3]: “There is a natural law which states that you can never get more out of a mincing machine, than what you have put into it. That is, if the reinsurance people want actuarially sound premiums, they must get a decent information about the claim distribution”. In more mathematical language: The brilliant idea of Bobbie Beard is unfortunately leading to a non-robust procedure. A deviation in the true (but unknown) underlying distribution may lead to completely different results.

In any case the mincing machine argument seemed so powerful that we have had little reconsideration of the above problem at subsequent ASTIN colloquia. It may therefore be worthwhile to have another look at the problem now, i.e. more than ten years after the Trieste colloquium.
Caisse nationale suisse d'assurance en cas d'accidents: résultats de la Statistique des Accidents de la Huitième Période Quinquennale 1953–1957
Authors: Koch Hans
Published: July 2016

La Caisse nationale suisse d'assurance en cas d'accidents à Lucerne, chargée du service de l'assurance obligatoire en cas d'accidents en Suisse, a publié il y a quelque temps les „Résultats de la statistique des accidents de la huitième période quinquennale 1953-1957”. Cette publication, qui est la huitième, paraît tous les cinq ans en français et en allemand). Ces différents rapports donnent un aperçu intéressant de la situation de l'assurance-accidents obligatoire en Suisse. Ils constituent dans leur ensemble une documentation précieuse touchant l'un des aspects du développement de la sécurité sociale en Suisse depuis 1918. C'est en effet à cette date que l'assurance obligatoire en cas d'accidents est entrée en vigueur et que la Caisse nationale suisse d'assurance en cas d'accidents, établissement de droit public autonome, a commencé son activité.

Le dernier rapport sera aussi consulté avec fruit par quiconque s'intéresse aux problèmes de l'assurance sociale. Cette publication d'environ 180 pages, illustrée par de nombreux tableaux, graphiques et illustrations, fournit une quantité d'indications très utiles présentées de façon claire. Les premiers chapitres sont surtout consacrés aux statistiques tirées du règlement des sinistres, tandis que les derniers chapitres traitent de quelques problèmes d'assurance spéciaux qui sont particulièrement actuels.
Bemerkungen zur Berechnung der Schwankungsrückstellung in der Brandversicherung
Authors: Hofmeister Emmi
Published: July 2016

In dem vorliegenden Artikel werden verschiedene Berechnungsmethoden diskutiert. Mit Hilfe mathematischer Tests werden die den Näherungsverfahren zugrundeliegenden Annahmen überprüft. Ausserdem ergibt ein Vergleich der Ergebnisse nach den verschiedenen Methoden einen Überblick bezüglich der Grenzen, in denen die Schwankungsrückstellung liegen sollte.

Die exakte Berechnung der benötigten Reserve ist nach den Methoden der kollektiven und auch der individuellen Risikotheorie nur möglich über die Verteilungsfunktion des Gesamtschadens. Wegen der auftretenden Faltungspotenzen der Verteilungsfunktion der Schadenshöhe sind diese Formeln sehr kompliziert. Man ist daher gezwungen bei praktischen Berechnungen von Näherungsformeln auszugehen.

Die einzelnen Verfahren unterscheiden sich wesentlich in den über die Schadensverteilung gemachten Annahmen. Es wird entweder die Verteilungsfunktion unmittelbar aus den Beobachtungsergebnissen hergeleitet oder von bekannten Verteilungsgesetzen, wie z.B. dem Poisson-Gesetz, ausgegangen.
Application of Game Theory to Some Problems in Automobile Insurance
Authors: Borch Karl
Published: July 2016

In this paper we shall study the problem of determining “correct” premium rates for sub-groups of an insurance collective. This problem obviously occurs in all branches of insurance. However, it seems at present to be a really burning issue in automobile insurance. We shall show that the problem can be formulated as a conflict between groups which can gain by co-operating, although their interests are opposed. When formulated in this way, the problem evidently can be analysed and solved by the help ot the “Game Theory” of Von Neumann and Morgenstern (5).

We shall first illustrate the problem by a simple example. We consider a group of n1 = 100 persons, each of whom may suffer a loss of 1, with probability p1 = 0.1. We assume that these persons consider forming an insurance company to cover themselves against this risk. We further assume that for some reason, government regulations or prejudices of managers, an insurance company must be organized so that the probability of ruin is less than 0.001

If such a company is formed, expected claim payment will be

and the standard deviation of the claim payments will be

If the government inspection (or the company's actuary) agrees that the ruin probability can be calculated with sufficient approximation by assuming that the claim payments have a normal distribution, the company must have funds amounting to
Note Concerning the Distribution Function of the Total Loss Excluding the Largest Individual Claims
Authors: Ammeter Hans
Published: July 2016

The theory of extreme values is a special branch of mathematical statistics and was mainly treated by E. J. Gumbel [4]). This theory has only been applied in a few cases to problems in the insurance business. The first practical application to insurance known to the author of the present paper is due to A. Thépaut who has invented a new reinsurance system called ECOMOR [5]. According to this system the reinsurer covers the excess risk for the m largest claims and the ceding company retains an amount equal to the (m + I) largest claim. The credit for having pointed out the importance of the theory of extreme values belongs to R. E. Beard [1]. Recently E. Franckx [3] has found a most remarkable result by disclosing the general form of the distribution for the largest claim occurring in a certain accounting period.

The present paper starts from the consideration that not only is the distribution of major claims, which might be eliminated by means of reinsurance, of interest to an insurer but also the distribution of the remaining total loss after excluding the largest claims. The nature of this distribution is important not only in connection with stability and security, but also for statistical investigations of the observed claim ratio. The credibility of such an investigation might be greatly improved if a suitable number of major claims were excluded. To simplify matters, the present paper considers the case where only the largest claim is excluded.
Theorie des valeurs extremes et la tarification de l'excess of loss
Authors: D'Hooge L.
Published: July 2016

Soit x1 ≤ x2, ≤ … ≤ xn—m + 1 ≤… ≤xn—p+1≤…≤ xn un échantillon ordonné de taille n d'une distribution dont F(x) et T(x) sont respectivement la fonction de répartition et la fonction de densité.

Nous appelons xn—m+1 la valeur de rang m de l'échantillon (x1, x2,…xn).

Pour simplifier l'écriture nous remplacerons partout l'indice n — m + I par m.

Avec cette convention nous notons la valeur caractéristique de rang m et l'intensité de rang m respectivement par um et αm [I].

Par définition on a:

Notons enfin par Fm (x) et Tm (x) la fonction de répartition et la fonction de densité de xm pour n → ∞ et m fixe.

2.1. Avant de résumer les différents points traités dans cette note, rappelons les particularités qui caractérisent la distribution asymptotique de la plus grande valeur x1 d'un échantillon. On sait que cette distribution existe si et seulement si la fonction de répartition F(x) appartient à un des trois types suivants [2]:

a) Type I: F(x) est du type exponentiel.

Le domaine de x est illimité vers la droite et F(x) tend vers I pour x → + ∞ au moins aussi rapidement qu'une fonction exponentielle.

Tous les moments de F(x) existent.

b) Type II: F(x) est du type de Cauchy.

Le domaine de x est illiminté vers la droite.
An Outline of a Generalization — started by E. Sparre Andersen — of the classical Ruin Theory
Authors: Thorin Olof
Published: July 2016

E. Sparre Andersen [1]) presented to the XVth International Congress of Actuaries, New York, 1957, a model of a collective risk process with a positive gross risk premium where the epochs of claims formed a renewal process. Let Ψ(u) (where u denotes the original risk reserve) denote the ruin probability in this model. Generalizing the classical result Sparre Andersen deduced the inequality

where R is a suitable positive number depending on the distribution function (continuous to the right), P(y), — ∞ < y < ∞, P(o) < 1, for the amounts of claims in case a claim occurs and also depending on the distribution function, K(t), t > o, K(o) = o, for the times between the epochs of successive claims, (The times between the epochs of successive claims, the inter-occurrence times, are assumed to be independent and identically distributed random variables. The time between the starting point and the epoch of the first claim is assumed to be independent of and to have the same distribution function as the inter-occurrence times. The amounts of claims are assumed to be independent of each other and of the epochs of claims and to be identically distributed.)
Quelques observations statistiques sur la variable „nombre de sinistres” en assurance automobile
Authors: Thyrion P.
Published: July 2016

Cette note ne risque pas de prêter le flanc à une critique souvent adressée à ASTIN, l'excès de spéculations mathématiques. Elle s'expose plutôt au reproche contraire, car elle a été, autant que possible, délibérément dépouillée de considérations théoriques, pour s'en tenir à quelques constatations arithmétiques fort simples sur la variable „Nombre de sinistres”.

Ces constatations sont orientées vers la pratique, particulièrement vers la mise en œuvre d'un système de bonus-malus.
Estimation of the number of excess claims by means of the credibility theory
Authors: Straub E.
Published: July 2016

The purpose of this paper is to describe a possible application on the rating of excess of loss covers of Mr. Bühlmann's work on Experience Rating and Credibility). One of the most important problems in connection with the rating of such treaties consists in estimating the number of excess claims and the average excess claim amount. Especially with cases where claims data are scarce there is a temptation to estimate these two quantities by means of the credibility theory. This approach leads, on the one hand, to a relatively complicated formula when considering the average excess claim amount, and, on the other, to a rather simple one for the credibility factor of the number of excess claims.
Ruin Probability During A Finite Time Interval
Authors: Beard R. E.
Published: July 2016

This paper was inspired by comments by H. L. Seal in a series of lectures given to the Actuaries Club in New York and by a paper of his recently published in the Swiss Actuarial Journal (Seal, 1972 [6]). In his lectures he showed that the probability U(w, t) that a risk reserve at every epoch τ, where o < τ ≤ t will be non negative when the initial risk reserve is w is related to , the probability that the aggregate claim outgo through epoch t does not exceed by the relationship

where η is the security loading and f(x, t) = (∂/∂x) F(x, t).

It is assumed that the d.f. F(x, t) is differentiable eith regard to x with a possible exception at the point x = o.

Using an extension of the “ballot theorem” in Chapter III of Feller (1968 [4]) he showed that and observed that if numerical values of F(x, t) were available values of U(w, t) could be computed.
The Story Of 100 Actuarially Guaranteed No-Ruin Casualty Insurance Companies
Authors: Seal Hilary L.
Published: July 2016

“Most people think that an insurance company's business is to make money out of insuring things. They are wrong. Its business is to take as much money off the public as possible, invest it successfully and hope that the conditions on which it was taken never happen.”

The Economist, April 13, 1974 (p. 119)

In order to motivate the series of Monte Carlo simulations we have carried out in the following article we would like readers to imagine that a small rural casualty insurance company, the Farm Fire and Flood Damage Ins. Co. (FFFDIC), is to be bought by an entrepreneur (whom we shall designate by EP) provided his consulting actuary (the author of this article) can satisfy his requirements which are as follow:

(i) A 15-year investment is foreseen at the end of which time EP wishes to be able to sell, hopefully without loss.

(ii) The risk-capital is to be invested and (although some of it must be in easily liquidable securities) should yield a rate of return comparable with that obtainable on the same amount of capital invested in the market.

(iii) The premiums will not have risk-loadings, as such, but will be loaded for profit by 15%.

(iv) The risk-capital should, on the average, be returnable at the end of the 15-year investment.
Deductibles In Industrial Fire Insurance
Authors: Strauss Jürgen
Published: July 2016

In recent times, the subject of deductibles in Industrial Fire insurance has gained significance to an increasing extent. In fact, up to a short time ago it was by no means common to apply deductibles in Industrial Fire insurance in Europe. The situation is entirely different in the USA where deductibles are the usual thing and are even obligatory with individual risk categories (e.g. petroleum refineries), hazards (e.g. explosion), or special types of companies (e.g. factory mutuals).

Today, however, there is a definite increase in the demand for deductibles in Industrial Fire insurance in Europe, too.

This trend may be explained by the fact that in order to reorganize their business successfully, insurers have been forced to increase their premiums by a considerable amount. It seems to be an unwritten law that when premiums in general are increased considerably, the point will some time or other be reached when the insured do not accept any further premium increases. Thus, even if such increases are completely justified in a view of claims experience, the insured will demand that premiums are reduced either by the insurer granting rebates for appropriate loss prevention measures or by the introduction of deductibles. In the USA, for example, such a situation arose around 1960 when considerable premium increases very quickly led to the introduction of substantial deductibles in Industrial business. In some European countries we are currently experiencing a similar development.
An Estimation of Claims Distribution
Authors: Eshita Nawojiro
Published: July 2016

There are two phases of difficulties in estimating a claims distribution. If we are going to estimate the claims distribution as accurately as possible, we should gather considerably long terms statistics. While economical and social environment will change. As a result the statistics gathered should be amended by a kind of trend value. One of difficulties here is the estimation of that trend value. Another difficulty is the estimation of claims distribution as being the stochastic distribution. In the case of considering claim size, the estimation becomes more difficult.

The intention of this paper is to propose an actual way of estimating stochastic claims distribution considering various kind of claim size by the use of a computer. Regarding the problem of amending claims distribution by a trend Value I will discuss at another time.
How Insolvent are We?
Authors: Johnson P. D.
Published: July 2016

As we grapple with the problems of conducting non-life insurance in a world of high inflation, we should perhaps pause for a moment to look for historical analogies for our present predicament. Let us, then, look back at a distressing period many years ago in the history of the Kingdom of Carmania.

Inflation was by no means new to the citizens of Carmania. Year after year, all prices and incomes had been rising at a steady rate of 5% per annum. The economy functioned quite well, albeit in a rather uninteresting way, and the people were accustomed to the idea that the purchasing power of the Carmanian dollar would fall by roughly 5% every year. There were, however, some economists who argued that inflation was both undesirable and unnecessary, and prevailed upon the King to adopt some measures which, they assured him, would quickly reduce the rate of inflation to zero. The measures were adopted, and the following year the rate of inflation rose to 10%.

At this point a rival group of economists explained that this unfortunate development was simply what should have been expected, and they set out an alternative policy which would undoubtedly reverse the trend and bring inflation quickly under control. Convinced by the weight of their arguments, the King introduced what became known as Phase 2 of the counter-inflation policy. By the next year, the rate of inflation had risen to 20%.
The Gerber-shiu Expected Discounted Penalty-reward Function under an Affine Jump-diffusion Model
Authors: Avram Florin , Usabel Miguel
Published: July 2016

We provide a unified analytical treatment of first passage problems under an affine state-dependent jump-diffusion model (with drift and volatility depending linearly on the state). Our proposed model, that generalizes several previously studied cases, may be used for example for obtaining probabilities of ruin in the presence of interest rates under the rational investement strategies proposed by Berk & Green (2004).
Occurrence and spread of influenza A(H1N1)pdm09 virus infection in Norwegian pig herds based on active serosurveillance from 2010 to 2014
Authors: ER C. , SKJERVE E. , BRUN E. , FRAMSTAD T. , LIUM B.
Published: July 2016

The incursion of influenza A(H1N1)pdm09 virus was detected by Norway's active serosurveillance of its pig population in 2009. Since then, surveillance data from 2010 to 2014 revealed that 54% of 5643 herd tests involving 1567 pig herds and 28% of 23 036 blood samples screened positive for antibodies against influenza A virus. Positive herds were confirmed to have influenza A(H1N1)pdm09 virus infection by haemagglutination inhibition test. In 50% of positive herd tests, ⩾60% of the sampled pigs in each herd had antibodies against influenza A(H1N1)pdm09 virus. This within-herd animal seroprevalence did not vary for type of production, herd size or year of test. The overall running mean of national herd seroprevalence, and annual herd incidence risks fluctuated narrowly around the means of 45% and 32%, respectively, with the highest levels recorded in the three densest pig-producing counties. The probability of a herd being seropositive varied in the five production classes, which were sow pools, multiplier herds, conventional sow herds, nucleus herds, and fattening herds in descending order of likelihood. Large herds were more likely to be seropositive. Seropositive herds were highly likely to be seropositive the following year. The study shows that influenza A(H1N1)pdm09 virus is established in the Norwegian pig population with recurrent and new herd infections every year with the national herd seroprevalence in 2014 hovering at around 43% (95% confidence interval 40–46%).
ON ANALOGUES OF THE CHURCH–TURING THESIS IN ALGORITHMIC RANDOMNESS
Authors: PORTER CHRISTOPHER P.
Published: July 2016

In this article, I consider the status of several statements analogous to the Church–Turing thesis that assert that some definition of algorithmic randomness captures the intuitive conception of randomness. I argue that we should not only reject the theses that have appeared in the algorithmic randomness literature, but more generally that we ought not evaluate the adequacy of a definition of randomness on the basis of whether it captures the so-called intuitive conception of randomness to begin with. Instead, I argue that a more promising alternative is to evaluate the adequacy of a definition of randomness on the basis of whether it captures what I refer to as a “notion of almost everywhere typicality.” In support of my main claims, I will appeal to recent work in showing the connection between of algorithmic randomness and certain “almost everywhere” theorems from classical mathematics.
Grape Seed Proanthocyanidins Attenuate Anxiety-Like Behavior in an Experimental Model of Dietary-Induced Hypercholesterolemia in Rats
Authors: Alrefaie Zienab
Published: July 2016

Abstract. Objective: Grape seed proanthocyanidins have many health-protective effects. The present work aimed to assess their possible anxiolytic effects in dietary-induced hypercholesterolemia in rats. Methods: 30 Male Wistar rats were divided into 3 groups (n = 10): control (normal chow), high cholesterol (cholesterol and cholic acid chow) and high cholesterol + grape seed extract (hypercholesterolemic chow + grape seed extract, 100 mg/kg body weight/day). After 4 months, total cholesterol levels and animals’ behavior in the open field and elevated plus maze were assessed. Results: High-cholesterol diet elevated cholesterol levels (p < 0.001 vs control group), however, grape seed administration ameliorated this elevation (p < 0.001 vs high-cholesterol untreated group). In the open field, hypercholesterolemic rats showed increased periods of immobility (138 ± 20.3 seconds (s) vs 96.9 ± 14.5 in control rats p < 0.001) and time latency to enter field center (109 ± 18.3 s compared to 40.8 ± 10.5 s in the control group p < 0.001). Both parameters were reduced by grape seed treatment (p < 0.01, p < 0.001 vs the untreated hypercholesterolemic group, respectively). Elevated plus maze testing demonstrated higher closed-arm entries (5.5 ± 1.1 in hypercholesterolemic animals vs 3 ± 1.1 in the control group p < 0.001) and lower percentage of time spent in open arms (19.7 ± 3.5 % vs 35.8 ± 4.8 % in control rats p < 0.001). Grape seed extract significantly enhanced the percentage of time spent in open arms (p < 0.001 compared to hypercholesterolemic rats). Conclusion: The present results highlight the possible anxiolytic effect of grape seed proanthocyanidins in dietary-induced hypercholesterolemia.
How Escherichia coli lands and forms cell clusters on a surface: a new role of surface topography
Authors: Gu Huan , Chen Aaron , Song Xinran , Brasch Megan E. , Henderson James H. , Ren Dacheng
Published: July 2016

Bacterial response to surface topography during biofilm formation was studied using 5 μm tall line patterns of poly (dimethylsiloxane) (PDMS). Escherichia coli cells attached on top of protruding line patterns were found to align more perpendicularly to the orientation of line patterns when the pattern narrowed. Consistently, cell cluster formation per unit area on 5 μm wide line patterns was reduced by 14-fold compared to flat PDMS. Contrasting the reduced colony formation, cells attached on narrow patterns were longer and had higher transcriptional activities, suggesting that such unfavorable topography may present a stress to attached cells. Results of mutant studies indicate that flagellar motility is involved in the observed preference in cell orientation on narrow patterns, which was corroborated by the changes in cell rotation pattern before settling on different surface topographies. These findings led to a set of new design principles for creating antifouling topographies, which was validated using 10 μm tall hexagonal patterns.
Selective local lysis and sampling of live cells for nucleic acid analysis using a microfluidic probe
Authors: Kashyap Aditya , Autebert Julien , Delamarche Emmanuel , Kaigala Govind V.
Published: July 2016

Heterogeneity is inherent to biology, thus it is imperative to realize methods capable of obtaining spatially-resolved genomic and transcriptomic profiles of heterogeneous biological samples. Here, we present a new method for local lysis of live adherent cells for nucleic acid analyses. This method addresses bottlenecks in current approaches, such as dilution of analytes, one-sample-one-test and incompatibility to adherent cells. We make use of a scanning probe technology - a microfluidic probe - and implement hierarchical hydrodynamic flow confinement (hHFC) to localize multiple biochemicals on a biological substrate in a non-contact, non-destructive manner. hHFC enables rapid recovery of nucleic acids by coupling cell lysis and lysate collection. We locally lysed ~300 cells with chemical systems adapted for DNA or RNA and obtained lysates of ~70 cells/μL for DNA analysis and ~15 cells/μL for mRNA analysis. The lysates were introduced into PCR-based workflows for genomic and transcriptomic analysis. This strategy further enabled selective local lysis of subpopulations in a co-culture of MCF7 and MDA-MB-231 cells, validated by characteristic E-cadherin gene expression in individually extracted cell types. The developed strategy can be applied to study cell-cell, cell-matrix interactions locally, with implications in understanding growth, progression and drug response of a tumor.
TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
Authors: Vinagre João , Nabais Joana , Pinheiro Jorge , Batista Rui , Oliveira Rui Caetano , Gonçalves António Pedro , Pestana Ana , Reis Marta , Mesquita Bárbara , Pinto Vasco , Lyra Joana , Cipriano Maria Augusta , Ferreira Miguel Godinho , Lopes José Manuel , Sobrinho-Simões Manuel , Soares Paula
Published: July 2016

One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.
IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin
Authors: Saul Louise , Ilieva Kristina M. , Bax Heather J. , Karagiannis Panagiotis , Correa Isabel , Rodriguez-Hernandez Irene , Josephs Debra H. , Tosi Isabella , Egbuniwe Isioma U. , Lombardi Sara , Crescioli Silvia , Hobbs Carl , Villanova Federica , Cheung Anthony , Geh Jenny L. C. , Healy Ciaran , Harries Mark , Sanz-Moreno Victoria , Fear David J. , Spicer James F. , Lacy Katie E. , Nestle Frank O. , Karagiannis Sophia N.
Published: July 2016

B cells participate in immune surveillance in human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses in cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B cells in healthy volunteers and melanoma patients (n = 73) and CD22+ cells in melanoma and normal skin samples (n = 189). Normal and malignant skin featured mature IgG and CD22 mRNA, alongside mRNA for the transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses of publically-available data (n = 234 GEO, n = 384 TCGA) confirmed heightened humoral responses (CD20, CD22, AID) in melanoma. Analyses of 51 melanoma-associated and 29 normal skin-derived IgG sequence repertoires revealed lower IgG1/IgGtotal representation compared with antibodies from circulating B cells. Consistent with AID, comparable somatic hypermutation frequencies and class-switching indicated affinity-matured antibodies in normal and malignant skin. A melanoma-associated antibody subset featured shorter complementarity-determining (CDR3) regions relative to those from circulating B cells. Clonal amplification in melanoma-associated antibodies and homology modeling indicated differential potential antigen recognition profiles between normal skin and melanoma sequences, suggesting distinct antibody repertoires. Evidence for IgG-expressing B cells, class switching and antibody maturation in normal and malignant skin and clonally-expanded antibodies in melanoma, support the involvement of mature B cells in cutaneous immunity.
Prognostic and Clinicopathological Significance of Survivin Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Xie Yongpeng , Ma Xin , Gu Liangyou , Li Hongzhao , Chen Luyao , Li Xintao , Gao Yu , Fan Yang , Zhang Yu , Yao Yuanxin , Zhang Xu
Published: July 2016

Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68–4.79), CSS (HR = 2.36, 95% CI 1.41–3.95) and PFS (HR = 2.20, 95% CI 1.58–3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21–3.44), pathological T stage (RR = 2.19, 95% CI 1.75–2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61–3.25), distant metastasis (RR = 1.56, 95% CI 1.16–2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29–3.45), tumor size (RR = 1.49, 95% CI 1.24–1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features and it could serve as a biomarker for disease management.
Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein
Authors: Wei Chunli , Cheng Jingliang , Zhou Boxv , Zhu Li , Khan Md. Asaduzzaman , He Tao , Zhou Sufang , He Jian , Lu Xiaoling , Chen Hanchun , Zhang Dianzheng , Zhao Yongxiang , Fu Junjiang
Published: July 2016

TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment.
Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach
Authors: Chen Lei , Huang Tao , Zhang Yu-Hang , Jiang Yang , Zheng Mingyue , Cai Yu-Dong
Published: July 2016

Tumors are formed by the abnormal proliferation of somatic cells with disordered growth regulation under the influence of tumorigenic factors. Recently, the theory of “cancer drivers” connects tumor initiation with several specific mutations in the so-called cancer driver genes. According to the differentiation of four basic levels between tumor and adjacent normal tissues, the cancer drivers can be divided into the following: (1) Methylation level, (2) microRNA level, (3) mutation level and (4) mRNA level. In this study, a computational method is proposed to identify novel lung adenocarcinoma drivers based on dysfunctional genes on the methylation, microRNA, mutation and mRNA levels. First, a large network was constructed using protein-protein interactions. Next, we searched all of the shortest paths connecting dysfunctional genes on different levels and extracted new candidate genes lying on these paths. Finally, the obtained candidate genes were filtered by a permutation test and an additional strict selection procedure involving a betweenness ratio and an interaction score. Several candidate genes remained, which are deemed to be related to two different levels of cancer. The analyses confirmed our assertions that some have the potential to contribute to the tumorigenesis process on multiple levels.
A C-type lectin with an immunoglobulin-like domain promotes phagocytosis of hemocytes in crayfish Procambarus clarkii
Authors: Zhang Xiao-Wen , Wang Yue , Wang Xian-Wei , Wang Lei , Mu Yi , Wang Jin-Xing
Published: July 2016

C-type lectins are important immune molecules that participate in host defense response. The present work reports a novel C-type lectin (PcLec3) from the red swamp crayfish Procambarus clarkii. Sequence analysis found that PcLec3 encodes a polypeptide with252 amino acid residues, which contains an immunoglobulin-like domain (IG) and a C-type lectin domain (CTLD) arranged in tandem. Tissue distribution analysis indicated that PcLec3 is enriched expressed in hemocytes and hepatopancreas cells, in which PcLec3 was up-regulated following bacterial challenge by Vibrio anguillarum. Function analysis using recombinant full-length PcLec3, IG and CTLD proteins revealed that these recombinant proteins had the capacity to bind carbohydrates and bacteria, while IG determined the cell binding activity. However, only full-length PcLec3 promotes the phagocytic activity of hemocytes and subsequent clearance of invasive bacteria. Taken together, these results manifest that PcLec3 acts as a hemocyte adhesion molecule to promote hemocyte phagocytosis against invasive V. anguillarum.
Four new lanthanide–organic frameworks: selective luminescent sensing and magnetic properties
Authors: Ning Yan , Wang Lu , Yang Guo-Ping , Wu Yunlong , Bai Nannan , Zhang Wenyan , Wang Yao-Yu
Published: July 2016

Four new isostructural lanthanide–organic frameworks have been synthesized, which show 2D layer-by-layer structures, and exhibit highly selective and efficient luminescence sensing for Fe3+ and Cr6+ ions in aqueous solution.
Enhancement of the photocatalytic activity of a TiO2/carbon aerogel based on a hydrophilic secondary pore structure
Authors: Cui Hua'nan , Liang Zhenxing , Zhang JinZhong , Liu Hong , Shi Jianying
Published: July 2016

The surface/interface synergy effect plays a positive role on the spatial separation and utilization of electrons and holes in photocatalytic process, which suggests a potential strategy for designing high efficiency photocatalysts.
A mechanistic study of the EC′ mechanism – the split wave in cyclic voltammetry and square wave voltammetry
Authors: Song Peng , Fisher Adrian C. , Wadhawan Jay D. , Cooper Joshua J. , Ward Haydn J. , Lawrence Nathan S.
Published: July 2016

In this paper, a detailed investigation of electrochemical reactions coupled with homogenous chemical steps using cyclic voltammetry (CV) and square wave voltammetry (SWV) was carried out to study the electrocatalytic (EC′) mechanism.
Stable isotope analysis of dietary arginine accrual and disposal efficiency in male rats fed diets with different protein content
Authors: Rotondo Floriana , Sanz Tania , Fernández-López José-Antonio , Alemany Marià , Remesar Xavier
Published: July 2016

The administration of diets with different protein/energy ratios induce variable but distinctive responses in rats; an excessive protein content tends to decrease fat accumulation, but reversion of this ratio tends to increase adipose tissue mass.
Ionic liquid-based uranium(vi) extraction with malonamide extractant: cation exchange vs. neutral extraction
Authors: Gaillard Clotilde , Boltoeva Maria , Billard Isabelle , Georg Sylvia , Mazan Valérie , Ouadi Ali
Published: July 2016

The U(VI) extraction with DMDBMA is performed in the [C4mim][Tf2N] ionic liquid (IL) either as a cationic or a neutral species, without the help of IL ions. However, this does not prevent a noticeable pollution of the aqueous phase with the IL.
Base-promoted intramolecular cyclization of N-alkyl, N-propargylic β-enaminones for the synthesis of polysubstituted pyrroles
Authors: Yang Xiaobing , Wang Yang , Hu Fangzhong , Kan Xiaoli , Yang Chiming , Liu Jiahui , Liu Pei , Zhang Qichun
Published: July 2016

An efficient, mild, metal-free, base-mediated intramolecular cyclization of N-alkyl, N-propargylic β-enaminones has been realized for the generation of polysubstituted pyrrole derivatives.
FeOx@carbon yolk/shell nanowires with tailored void spaces as stable and high-capacity anodes for lithium ion batteries
Authors: Li Xueying , Ma Yuanyuan , Cao Guozhong , Qu Yongquan
Published: July 2016

Porous FeOx@C yolk/shell nanowires with optimized void space delivered a stable cyclability over 400 cycles, high capacities and a good rate capability. The optimized void space contributes to preserve structural integrity and maintain good electrical contact between FeOx and C.
A nitrogen doped carbonized metal–organic framework for high stability room temperature sodium–sulfur batteries
Authors: Chen Yu-Ming , Liang Wenfeng , Li Si , Zou Feng , Bhaway Sarang M. , Qiang Zhe , Gao Min , Vogt Bryan D. , Zhu Yu
Published: July 2016

A nitrogen-doped carbonized metal–organic framework was utilized for room temperature sodium sulfur batteries. The cZIF-8/S composite electrode exhibited good cyclability over 250 cycles at 0.2C with a specific capacity of 500 mA h g−1.
Late Occurrence of Sphenoid Pyocele after Pituitary Surgery
Authors: Kovoor George , Harsha Kamble , George Akash , Reddy Venkat
Published: July 2016

The transsphenoidal approach to lesions of the sella turcica, especially for pituitary tumors, has been favored by neurosurgeons because of decreased perioperative patient morbidity and mortality of this approach compared with others. It is widely accepted because of its minimally invasive and maximally effective procedure. We report a rare case of a 63-year-old female patient with the asymptomatic delayed occurrence of sphenoid pyocele, 6 years after the initial pituitary surgery, and remained asymptomatic during this long interval.