bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lentiviral HSV‐Tk.007‐mediated suicide gene therapy is not toxic for normal brain cells
Authors: Hossain Jubayer A. , Ystaas Lars Rømo , Mrdalj Jelena , Välk Kristjan , Riecken Kristoffer , Fehse Boris , Bjerkvig Rolf , Grønli Janne , Miletic Hrvoje 
Published: August 2016

AbstractBackgroundGene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV‐Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation.MethodsIn the present study, we tested lentiviral vectors delivering the suicide gene HSV‐Tk.007, a highly active mutant of HSV‐Tk, to rat brains as a preclinical toxicity study. We injected 106 vesicular stomatitis virus glycoprotein (VSV‐G) pseudotyped functional lentiviral particles harboring the suicide gene HSV‐Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14 days of GCV treatment, we analyzed HSV‐Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis.ResultsDuring prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV‐Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed.ConclusionsWe show that HSV‐Tk.007‐mediated suicide gene therapy is not toxic to normal brain cells. This observation is of high relevance for the translation of lentivirus‐mediated suicide gene therapies into the clinic for the treatment of brain tumor patients. Copyright © 2016 John Wiley & Sons, Ltd.
The bile acid chenodeoxycholic acid directly modulates metabolic pathways in white adipose tissue in vitro: insight into how bile acids decrease obesity
Authors: Teodoro João Soeiro , Rolo Anabela Pinto , Jarak Ivana , Palmeira Carlos Marques , Carvalho Rui Albuquerque 
Published: August 2016

AbstractObesity is a worldwide epidemic, and associated pathologies, including type 2 diabetes and cardiovascular alterations, are increasingly escalating morbidity and mortality. Despite intensive study, no effective simple treatment for these conditions exists. As such, the need for go‐to drugs is serious. Bile acids (BAs) present the possibility of reversing these problems, as various in vivo studies and clinical trials have shown significant effects with regard to weight and obesity reduction, insulin sensitivity restoration and cardiovascular improvements. However, the mechanism of action of BA‐induced metabolic improvement has yet to be fully established. The currently most accepted model involves non‐shivering thermogenesis for energy waste, but this is disputed. As such, we propose to determine whether the BA chenodeoxycholic acid (CDCA) can exert anti‐obesogenic effects in vitro, independent of thermogenic brown adipose tissue activation. By exposing differentiated 3 T3‐L1 adipocytes to high glucose and CDCA, we demonstrate that this BA has anti‐obesity effects in vitro. Nuclear magnetic resonance spectroscopic analysis of metabolic pathways clearly indicates an improvement in metabolic status, as these cells become more oxidative rather than glycolytic, which may be associated with an increase in fatty acid oxidation. Our work demonstrates that CDCA‐induced metabolic alterations occur in white and brown adipocytes and are not totally dependent on endocrine/nervous system signaling, as thought until now. Furthermore, future exploration of the mechanisms behind these effects will undoubtedly reveal interesting targets for clinical modulation.
Modification of human serum albumin by the nerve agent VX: microbore liquid chromatography/electrospray ionization high‐resolution time‐of‐flight tandem mass spectrometry method for detection of phosphonylated tyrosine and novel cysteine containing disulfide adducts
Authors: Kranawetvogl Andreas , Worek Franz , Thiermann Horst , John Harald 
Published: August 2016

RationaleOrganophosphorus nerve agents still constitute a considerable threat to the health of military personnel and the civilian population. Long‐term biomarkers are crucial for reliable verification of exposure to banned substances. Therefore, current research focuses on identification of endogenous protein targets showing covalent modifications by organophosphorus nerve agents (adducts).MethodsPurified human serum albumin and human plasma were incubated with the nerve agent VX followed by enzymatic proteolysis with pronase. Resulting peptide cleavage products were separated by microbore liquid chromatography (μLC) online coupled to positive electrospray ionization (ESI) with subsequent high‐resolution time‐of‐flight tandem mass spectrometry (HR MS/MS) allowing identification of known and novel adducts.ResultsIn addition to known phosphonylation of various tyrosine residues, albumin was found to be modified at diverse cysteine residues by covalent attachment of the leaving group of VX. These novel disulfide adducts were cleaved from at least two regions of the intact protein as dipeptides containing cysteine and proline either as CP or PC. A rapid and sensitive method was developed for simultaneous detection of the diverse covalent modifications of human albumin by VX.ConclusionsIdentification of the novel leaving group adducts with human albumin expands the basic knowledge on molecular toxicology of the nerve agent VX. Furthermore, the presented μLC/ESI HR MS/MS method might be of relevance for verification of VX poisoning. Copyright © 2016 John Wiley & Sons, Ltd.
New results on the Earth insolation and their correlation with the Late Pleistocene paleoclimate of West Siberia
Authors: Smulsky J.J. 
Published: August 2016

Abstract
The three problems composing the astronomical theory of paleoclimate have been solved in a new way. Two of them (changes in the orbital motion of the Earth and its insolation) have confirmed the results of previous research. In the third problem (a change in the rotational motion of the Earth), the obtained oscillations of the Earth’s rotation axis have an amplitude seven–eight times higher than the earlier estimated one. They lead to changes in insolation, which explain the paleoclimatic fluctuation. The changes in insolation and its structure for 200 kyr are considered. It is shown that the Late Pleistocene key events in West Siberia, for example, the last glaciations and warming between them, coincide with the extremes of insolation. The insolation periods of paleoclimatic changes and their characteristics are given.
High-frequency induction logging in deviated and horizontal wells: Geosteering and inversion
Authors: Gorbatenko A.A. , Sukhorukova K.V. 
Published: August 2016

Abstract
The study focuses on processing methods for high-frequency induction data from deviated and horizontal wells. Simulation of electromagnetic fields with analytical algorithms is used to study how the resistivity of rocks above and below the well influences the acquired data. The simulations show that the contribution of under- and overlying layers into the recorded responses is considerable and depends on resistivity contrasts between the layers and on the position of logging arrays relative to the layer boundaries. This fact has to be taken into account when estimating true resistivity of reservoirs and when inverting induction logs from horizontal wells for reservoir characterization. The method is applied to oil- and water-saturated reservoirs in West Siberia, which contain high-resistivity impermeable layers leading to overestimation of apparent resistivity. Due regard for the effect of these layers in inversion of induction logs provides high-quality resistivity estimates.
Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women
Authors: Wong Rachel H.X. , Evans Hamish M. , Howe Peter R.C. 
Published: August 2016

AbstractIntroductionImpairment of cerebrovascular function becomes evident after menopause. No study has yet explored relationships between deficits in cerebrovascular function, cognitive performance, and mood in postmenopausal women.MethodCerebrovascular function was assessed in 80 healthy postmenopausal women by monitoring blood flow velocity (BFV) in the middle and posterior cerebral arteries using transcranial Doppler ultrasound at rest, following a hypercapnic challenge, and during performance of a cognitive test battery; the latter assessed domains of memory and executive functions. Various measures of mood (i.e., Profile of Mood States and Center for Epidemiological Studies Depression Scale) were also assessed.ResultsCerebral artery elasticity and BFV responsiveness to cognitive tests (neurovascular coupling) correlated with cognitive performance but not with depressive symptoms or mood states. Mood deficits were related to poor cognitive performance.ConclusionThese results highlight the importance of adequate cerebral perfusion for optimized cognitive function in healthy postmenopausal women. Preventative strategies to attenuate accelerated cognitive decline should also consider restoring cerebrovascular function.
Discounted Bonus Policies
Authors: Hustwitt W. E. 
Published: August 2016

The principle underlying all Discounted Bonus Schemes is that the ordinary full profit premium is reduced by anticipating future bonuses. These reduced premium policies are then usually allowed to participate in future bonuses but only in so far as the bonus declared exceeds that anticipated.This class of business was first introduced in 1854, and eventually became popular with a section of the assuring public to whom the benefit of a with-profit policy at a minimum cost made a strong appeal. In the first instance the Discounted Bonus policy made its appearance in connection with a compound reversionary bonus system, but as it grew in popularity it was adopted by other offices and combined with the various methods of bonus distribution.
I. An approximation to the yield on a redeemable security, allowing for income tax
Authors: Worger H. O. 
Published: August 2016

Redemption yields on redeemable securities may conveniently be found with the aid of tables of Bond Values. These tables make no allowance for the fact that income tax is payable on the full dividend payments with no adjustment for profit or loss on redemption.Those investors who are taxed on the full dividends require to know the net yield after allowing for tax, or, more usually, the gross equivalent of this net yield, commonly known as the “equivalent gross yield”. It is often inconvenient to deduct tax from the dividend rate and find the net yield direct, as the net dividend frequently does not coincide with the rates for which tables are available. There is, however, a very convenient and extremely accurate approximation to the required equivalent gross yield which is as follows:To find the equivalent gross yield, reduce the unexpired term in proportion to the rate of tax payable and enter the table for the full nominal dividend rate.
Disability benefits in conjunction with life assurance policies
Authors: Purchase H. F. 
Published: August 2016

Disability Insurance is a subject which has at various times found a place in the proceedings of the Faculty and Institute of Actuaries, but only on rare occasions at our own proceedings. The present paper does not present anything new on the subject but has been written with the object of providing an opportunity of considering and discussing a form of insurance which, in some form or other, is transacted by most Life Offices in this country. Most Life Offices will only issue a somewhat mild form of the insurance, that is, the Waiver of Premium benefit, but even if we are not usually concerned with more than this form of the insurance, it is felt that a discussion of the principles involved would be of value.Considering the number of eminent actuaries who have, at various times, stated that they would like to see an extension of the writing of Disability Insurance, it is somewhat surprising that more of the business has not been written in this country. The reasons for the neglect are not far to seek. First, there are very real administrative difficulties involved including the difficulty of obtaining suitable statistics on the subject. A large part of the present paper is taken up with a discussion of these difficulties. Secondly, there is the unfortunate experience of our American colleagues who have in the past lost considerable sums of money in their Disability Accounts. This experience has led a large number of American Offices to cease to transact the more liberal forms of benefit.
The apportionment of a trust fund by mutual consent of all the beneficiaries
Authors: Goodchild W. P. 
Published: August 2016

In advising on the apportionment of a fund, an actuary is faced with practical problems of admitted difficulty. The following notes are an attempt to discover exactly what these problems are, and to determine the methods of approach most likely to lead to a satisfactory solution.Trustees looking after a settled fund have a different attitude to investment from that of persons controlling the investments of a life assurance fund. The funds of a life office are normally increasing; in such a case it is easy to see that the object of investment policy is to secure accumulation at as rapid a rate as is consistent with safety. Changes in the portfolio can be considered which do not necessarily result in an immediate increase in current income. The securing of a capital profit or the avoidance of a prospective capital loss by a sale and reinvestment may be a valuable source of strength. Trustees, on the other hand, cannot ignore the importance of a high level of current income, for a trust fund is normally invested to produce income for disbursement, and there is a vital distinction between trust ‘capital’ and ‘income’.
Consistent Extra Premiums and Equivalent Decreasing Debts for Endowment Assurances.
Authors: Sandom K. 
Published: August 2016

This article attempts to develop a practical system for dealing with extra-risks whilst retaining consistency in the terms offered to proposers. The extra premiums derived vary according to the view taken of the incidence of the extra-risk, and tables are produced to enable the underwriter to deduce quickly the required special terms.W. Perks' paper, ‘The Treatment of Sub-Standard Lives in Practice’ (J.I.A.78, 205), describes a system whereby the special terms are fixed according to uniform percentage increases in mortality throughout the term. This approach does not make a broad assessment of the incidence of the extra-risk. The present writer feels that some allowance for incidence should be made, and the process that follows attempts to adhere to the narrow theoretical path. The scope of this article does not include the interesting fields of underwriting practice and experience which were admirably discussed in W. Perks' paper.
A Method of Determining the Future Trend of a Pension Fund by Means of a Series of Notional Valuations
Authors: Merriman P. E. 
Published: August 2016

In a recent paper to the Students' Society (J.S.S.15, 43), D. F. Gilley and D. Funnell pointed out that it would be theoretically possible, though normally impracticable, to make a valuation of a pension fund by projecting the fund membership year by year, in order to obtain a series of notional revenue accounts for each future year of the Fund's existence, and that the algebraic sum of the discounted values of the expected future current surpluses and/or deficits would be equal to the surplus or deficiency revealed by a valuation made in the normal way.It is frequently possible, when an estimate of the future trend of the fund is required, to reverse this process. Instead of directly estimating the future income and outgo of the fund, and so building up the expected amount of the fund year by year, we may extend the normal valuation technique, and use a series of notional valuations to determine the future trend of the Fund. In other words, the growth or decline of a pension fund between two future dates may be expressed as the difference between the net liabilities of the fund, as revealed by notional valuations, on these two dates.
Friendly Societies and the Actuary.
Authors: Lane R. C. B. 
Published: August 2016

On being asked to prepare something on Friendly Societies for the Students' Society it seemed reasonable to attempt two things—one, to put them more into perspective in modern conditions, the other, to see what they might be able to teach the actuary professionally. The following notes are the result: it is hoped that, besides forming a useful basis for the discussion, they will themselves have something worth while to contribute to the subject.Perhaps the most important characteristic of a Friendly Society is its registration under the Friendly Societies Acts (the relatively rare occurrence of an unregistered society is ignored); the restrictions of these acts have therefore to be accepted for the sake of their advantages. The constitution is a book of rules and the government is in the hands of the trustees—in whose names the assets are registered—and a committee appointed by the members at a general meeting. The rules cover all such matters as objects, eligibility, benefits, contributions, duties of officers, changes of rules, of name, nominations, dissolutions, investments and so on as required by good sense and the Acts.
Management Development
Authors: Ryder D. 
Published: August 2016

I am delighted to be able to speak to you tonight. In view of the pressures on my programme at the moment, you may feel that my delight is a bit shallow but I can assure you that it is not. It is a most refreshing and agreeable change to be talking to members of a profession that I do not cross swords with! In fact, I do have the very greatest respect for your profession and I am sure that what I have to say this evening,shouldbe relevant. I intend to talk about Management Development and I am sure that you will agree that Actuaries are themselves managers: they are managers of money in one form or another and I become particularly interested when it ismymoney that they are managing. So any help that I may be able to give you most certainlyisgiven with a personal and ulterior motive.I want what I say tonight to be as practically based as possible, and for this reason I shall be talking mainly about Reed International. I want to tell you some of the ways in which managers should be—and are being—developed in Reed.
An Ancient Chinese Stock of Gold
Authors: Dubs Homer H. 
Published: August 2016

The elaborate Chinese standard histories, which, if all translated, would fill several hundred thick volumes, provide illuminating information about many aspects of economic history. In this paper, I shall present a passage that enables us to estimate the gold stock of the Chinese at the beginning of the Christian era, a type of information rarely available.In his History of the Former Han Dynasty, Ban Gu (writing about A.D. 80) has occasion to illustrate the stinginess of a usurping emperor, Wang Mang, and enumerates his wealth as follows:At this time [A.D. 23], in the inner apartments of the Wei-yang Palace, ten thousand catties of actual gold were put into one chest and there still remained sixty chests. In each office for storage of the Yellow Gate and of the Intendant of Palace Parks and in the workshops of the Master of Recipes, there were also several chests. The Imperial Treasury at the Ch'ang-lo Palace and the Bureau of Equalization and Standards in the capital in addition stored very much cash, silk, pearls, jade, and valuables.
‘Photosystem II: the water splitting enzyme of photosynthesis and the origin of oxygen in our atmosphere’
Authors: Barber James 
Published: August 2016

AbstractAbout 3 billion years ago an enzyme emerged which would dramatically change the chemical composition of our planet and set in motion an unprecedented explosion in biological activity. This enzyme used solar energy to power the thermodynamically and chemically demanding reaction of water splitting. In so doing it provided biology with an unlimited supply of reducing equivalents needed to convert carbon dioxide into the organic molecules of life while at the same time produced oxygen to transform our planetary atmosphere from an anaerobic to an aerobic state. The enzyme which facilitates this reaction and therefore underpins virtually all life on our planet is known as Photosystem II (PSII). It is a pigment-binding, multisubunit protein complex embedded in the lipid environment of the thylakoid membranes of plants, algae and cyanobacteria. Today we have detailed understanding of the structure and functioning of this key and unique enzyme. The journey to this level of knowledge can be traced back to the discovery of oxygen itself in the 18th-century. Since then there has been a sequence of mile stone discoveries which makes a fascinating story, stretching over 200 years. But it is the last few years that have provided the level of detail necessary to reveal the chemistry of water oxidation and O–O bond formation. In particular, the crystal structure of the isolated PSII enzyme has been reported with ever increasing improvement in resolution. Thus the organisational and structural details of its many subunits and cofactors are now well understood. The water splitting site was revealed as a cluster of four Mn ions and a Ca ion surrounded by amino-acid side chains, of which seven provide direct ligands to the metals. The metal cluster is organised as a cubane structure composed of three Mn ions and a Ca2+linked by oxo-bonds with the fourth Mn ion attached to the cubane. This structure has now been synthesised in a non-protein environment suggesting that it is a totally inorganic precursor for the evolution of the photosynthetic oxygen-evolving complex. In summary, the overall structure of the catalytic site has given a framework on which to build a mechanistic scheme for photosynthetic dioxygen generation and at the same time provide a blue-print and incentive to develop catalysts for artificial photo-electrochemical systems to split water and generate renewable solar fuels.
Appendix: the Thermoluminescence Tests
Authors: Bowman S. G. E. 
Published: August 2016

Thermoluminescence (TL) applied to the dating and authenticity testing of ancient ceramics is a well established technique.Thermoluminescence is the light given out by non-conducting crystalline materials as a result of exposure to radiation and subsequent heating. In pottery the crystalline inclusions, such as quartz and feldspars, are responsible for the TL. The radiation results from minute quantities of radioactive impurities in the pottery itself and in its immediate environment. The TL signal measured in the laboratory is related to the time elapsed since either the formation of the crystalline inclusions or since they were last fired to a temperature of about 500°C or above. The dating of pottery by TL is therefore only possible due to the removal during firing by man of the effect of previous radiation over geological time. The TL signal is then proportional to the age of the pottery. When a ceramic is fired to a temperature which is not sufficient to remove the effect of previous radiation, the TL signal is normally in saturation, i.e. addition of a laboratory radiation dose prior to heating does not enhance the TL signal. In such cases, TL cannot be used to determine the authenticity or otherwise of the object.