Growth and carbon metabolism of the seaweed Fucus vesiculosus in the western Baltic Sea ("Kiel Outdoor Benthocosms")

Warming and acidification of the oceans as a consequence of increasing CO2-concentrations occur at large scales. Numerous studies have shown the impact of single stressors on individual species. However, studies on the combined effect of multiple stressors on a multi-species assemblage, which is ecologically much more realistic and relevant, are still scarce. Therefore, we orthogonally crossed the two factors warming and acidification in mesocosm experiments and studied their single and combined impact on the brown alga Fucus vesiculosus associated with its natural community (epiphytes and mesograzers) in the Baltic Sea in all seasons (from April 2013 to April 2014). We superimposed our treatment factors onto the natural fluctuations of all environmental variables present in the Benthocosms in so-called delta-treatments. Thereby we compared the physiological responses of F. vesiculosus (growth and metabolites) to the single and combined effects of natural Kiel Fjord temperatures and pCO2 conditions with a 5 °C temperature increase and/or pCO2 increase treatment (1100 ppm in the headspace above the mesocosms). Responses were also related to the factor photoperiod which changes over the course of the year. Our results demonstrate complex seasonal pattern. Elevated pCO2 positively affected growth of F. vesiculosus alone and/or interactively with warming. The response direction (additive, synergistic or antagonistic), however, depended on season and daylength. The effects were most obvious when plants were actively growing during spring and early summer. Our study revealed for the first time that it is crucial to always consider the impact of variable environmental conditions throughout all seasons. In summary, our study indicates that in future F. vesiculosus will be more affected by detrimental summer heat-waves than by ocean acidification although the latter consequently enhances growth throughout the year. The mainly negative influence of rising temperatures on the physiology of this keystone macroalga may alter and/or hamper its ecological functions in the shallow coastal ecosystem of the Baltic Sea.

Age models of sediment cores from the North-West African continental margin

A statistical analysis ol 15 deep sea cores in the eastern North Atlantic off NW Africa revealed the typical fluctuation pattern of distinct species proups as has been described from various parts of the world ocean. Only the "WBF-group" appears to be correlated with global climatic changes, i.e. warmer periods as the Eemian and the Atlanticum. A partly antagonistic "High Productivity group" (HPR-group) is in general not linked with global changes but times of increased fertility in the surface water and the resulting flux of organic matter reaching the bottom. The groups were extracted from cluster analysis of more than 150 surface samples (HPR-group) and a factor analysis of selected cores (WBF-group). In contrast to previous studies the observed fluctuations can not be explained by drastic changes in bottom water masses, but by the pulsation of a distinct "High Productivity Patch" in space and time. At present, this patch is located below the well known upwelling area between 22° and 12° northern latitude. It shifted to the north (up to 27 °N) during the latest glacial period ( 18 ky), indicating an equivalent shift of upwelling productivity caused by advection of nutrient rich upwelling SACW-waters, probably during most of isotopic stages 2 and 3.

Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

From apartheid to unity: white capital and black power in the racial integration of South African football, 1976-1992

This article analyses the complex process that deracialised and democratised South African football between the early 1970s and 1990s. Based mainly on archival documents, it argues that growing isolation from world sport, exemplified by South Africa's expulsion from the Olympic movement in 1970 and FIFA in 1976, and the reinvigoration of the liberation struggle with the Soweto youth uprising triggered a process of gradual desegregation in the South African professional game. While Pretoria viewed such changes as a potential bulwark against rising black militancy, white football and big business had their own reasons for eventually supporting racial integration, as seen in the founding of the National Soccer League. As negotiations for a new democratic South Africa began in earnest between the African National Congress (ANC) and the National Party (NP) in the latter half of the 1980s, transformations in football and politics paralleled and informed each other. Previously antagonistic football associations began a series of 'unity talks' between 1985 and 1986 that eventually culminated in the formation of a single, non-racial South African Football Association in December 1991, just a few days before the Convention for a Democratic South Africa (CODESA) opened the process of writing a new post-apartheid constitution. Finally, three decades of isolation came to an end as FIFA welcomed South Africa back into world football in 1992 - a powerful example of the seemingly boundless potential of a liberated and united South Africa ahead of the first democratic elections in 1994.

Toward the discovery of vaccine adjuvants:coupling in silico screening and in vitro analysis of antagonist binding to human and mouse CCR4 receptors

Background Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. Methodology Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4+ Tregs. Significance Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice.

Le prix de l'individualité. Maine de Brian, Samuel Taylor Coleridge et la volonté: Deux postétités distinctes

This thesis is concerned with Maine de Biran’s and Samuel Taylor Coleridge’s conceptions of will, and the way in which both thinkers’ posterities have been affected by the central role of these very conceptions in their respective bodies of thought. The research question that animates this work can therefore be divided into two main parts, one of which deals with will, while the other deals with its effects on posterity. In the first pages of the Introduction, I make the case for a comparison between two philosophers, and show how this comparison can bring one closer to truth, understood not in objective, but in subjective terms. I then justify my choice by underlining that, in spite of their many differences, Maine de Biran and Samuel Taylor Coleridge followed comparable paths, intellectually and spiritually, and came to similar conclusions concerning the essential activity of the human mind. Finally, I ask whether it is possible that this very focus on the human will may have contributed to the state of both thinkers’ works and of the reception of those works. This prologue is followed by five parts. In the first part, the similarities and differences between the two thinkers are explored further. In the second part, the connections between philosophy and singularity are examined, in order to show the ambivalence of the will as a foundation for truth. The third part is dedicated to the traditional division between subject and object in psychology, and its relevance in history and in moral philosophy. The fourth part tackles the complexity of the question of influence, with respect to both Maine de Biran’s and Coleridge’s cases, both thinkers being indebted to many philosophers of all times and places, and having to rely heavily on others for the publication, or the interpretation of their own works. The fifth part is concerned with the different aspects of the faculty of will, and primarily its relationship with interiority, as incommensurability, and actual, conditioned existence in a certain historical and spatial context. It ends with a return to the question of will and posterity and an announcement of what will be covered in the main body of the thesis. The main body is divided into three parts:‘L’émancipation’, ‘L’affirmation, and ‘La projection’. The first part is devoted to the way Maine de Biran and Samuel Taylor Coleridge extricated themselves from one epistemological paradigm to contribute to the foundation of another. It is divided in four chapters. The first chapter deals with the aforementioned change of paradigm, as corresponding to the emergence of two separate but associated movements, Romanticism and what the French philosopher refers to as ‘The Age of History’. The second chapter concerns the movement that preceded them, i.e. the Enlightenment, its main features according to both of our thinkers, and the two epistemological models that prevailed under it and influenced them heavily in their early years: Sensationism (Maine de Biran) and Associationism (Coleridge). The third chapter is about the probable influence of Immanuel Kant and his followers on Maine de Biran and Coleridge, and the various facts that allow us to claim originality for both thinkers’ works. In the fourth chapter, I contrast Maine de Biran and Coleridge with other movements and thinkers of their time, showing that, contrary to their respective thoughts, Maine de Biran and Coleridge could not but break free from the then prevailing systematic approach to truth. The second part of the thesis is concerned with the first part of its research question, namely, Maine de Biran’s and Coleridge’s conceptions of the will. It is divided into four chapters. The first chapter is a reflection on the will as a paradox: on the one hand, the will cannot be caused by any other phenomenon, or it is no longer a will; but it cannot be left purely undetermined, as if it is, it is then not different from chance. It thus needs, in order to be, to be contradictorily already moral. The second chapter is a comparison between Maine de Biran’s and Coleridge’s accounts of the origin of the will, where it is found that the French philosopher only observes that he has a will, whereas the English philosopher postulates the existence of this will. The comparison between Maine de Biran’s and Coleridge’s conceptions of the will is pursued in the third chapter, which tackles the question of the coincidence between the will and the self, in both thinkers’ works. It ends with the fourth chapter, which deals with the question of the relationship between the will and what is other to it, i.e. bodily sensations, passions and desires. The third part of the thesis focuses on the second part of its research question, namely the posterity of Maine de Biran’s and Coleridge’s works. It is divided into four chapters. The first chapter constitutes a continuation of the last chapter of the preceding part, in that that it deals with Maine de Biran’s and Coleridge’s relations to the ‘other’, and particularly their potential and actual audience, and with the way these relations may have affected their writing and publishing practices. The second chapter is a survey of both thinkers’ general reception, where it is found that, while Maine de Biran has been claimed by two important movements of thoughts as their initiator, Coleridge has been neglected by the only real movement he could have, or may indeed have pioneered. The third chapter is more directly concerned with the posterities of Maine de Biran’s and Coleridge’s conceptions of will, and attempts to show that the approach to, and the meaning of the will have evolved throughout the nineteenth century, and in the French Spiritualist and the British Idealist movements, from an essentially personal one to a more impersonal one. The fourth chapter is a partial conclusion, whose aim is to give a precise idea of where Maine de Biran and Coleridge stand, in relation to their century and to the philosophical movements and matters we are concerned with. The conclusion is a recapitulation of what has been found, with a particular emphasis on the dialogue initiated between Maine de Biran and Coleridge on the will, and the relation between will and posterity. It suggests that both thinkers have to pay the price of a problematic reception for the individuality that pervades their respective works, and goes further in suggesting that s/he who chooses to found his individuality on the will is bound to feel this incompleteness in his/her own personal life more acutely than s/he who does not. It ends with a reflection on fixedness and movement, as the two antagonistic states that the theoretician of the will paradoxically aspires to.

Broad direction bandwidths for complex motion mechanisms

Growing evidence from psychophysics and single-unit recordings suggests specialised mechanisms in the primate visual system for the detection of complex motion patterns such as expansion and rotation. Here we used a subthreshold summation technique to determine the direction tuning functions of the detecting mechanisms. We measured thresholds for discriminating noise and signal + noise for pairs of superimposed complex motion patterns (signal A and B) carried by random-dot stimuli in a circular 5° field. For expansion, rotation, deformation and translation we found broad tuning functions approximated by cos(d), where d is the difference in dot directions for signal A and B. These data were well described by models in which either: (a) cardinal mechanisms had direction bandwidths (half-widths) of around 60° or (b) the number of mechanisms was increased and their half-width was reduced to about 40°. When d = 180° we found summation to be greater than probability summation for expansion, rotation and translation, consistent with the idea that mechanisms for these stimuli are constructed from subunits responsive to relative motion. For deformation, however, we found sensitivity declined when d = 180°, suggesting antagonistic input from directional subunits in the deformation mechanism. This is a necessary property for a mechanism whose job is to extract the deformation component from the optic flow field. © 2001 Elsevier Science Ltd.

The behaviour of antioxidants in polyolefins under conditions of U.V. exposure

The effects of antioxidants and stabilizers on the oxidative degradation of polyolefins (low density polyethylene [LDPE] and polypropylene [PPJ have been studied after subjecting to prior high temperature processing treatments. The changes in the both chemical and physical properties of unstabilized polymers occurring during processing were found to be strongly dependent on the amount of oxygen present in the mixer. Subsequent thermal and photo-oxidation showed very similar characteristics and the chromophore primarily responsible for:both thermo and photooxidative degradation of unstabilized polymers was found to be hydroperoxide formed during processing. Removal of hydroperoxide by heat treatment in an inert atmosphere although increasing ketonic carbonyl concentration, markedly decreased the rate of photo-oxidation, introducing an induction period similar to that of an unprocessed sample. It was concluded that hydroperoxides are the most important initiators in normally processed polymers during the early stages of photo-oxidation. Antioxidants such as metal dithiocarbamates which act by destroying peroxides into non-radica1 products were found to be efficient melt stabilizers for polyolefins and effective UV stabilizers during the initial photo-oxidation stage, whilst a phenolic antioxidant, n-octadecyl-3-(3',5'-di-terbutyl 4'hydroxypheny1) propionate (Irganox 1076) retarded photo-oxidation rate in the later stages. A typical 'UV absorber' 2-hydroxy-4-octyloxy-benzophenone (HOBP) has a minor thermal antioxidant action but retarded photo-oxidation at all stages. A substituated piperidine derivative, Bis [2.2.6.6-tetramethylpiperidlnyl-4] sebacate (Tinuvin 770) behaved as an pro-oxidant during thermal oxidation of polyolefins but was an effective stabilizer against UV light. The UV absorber, HOBP synergised effectively with both peroxide decomposing antioxidants (metal dithiocarbamates) and a chain-breaking antioxidant (Irganox 1076) during photo-oxidation of the poymers studed whereas the combined effect was additive during thermal oxidation. By contrast, the peroxide decornposers and chain-breaking antioxidant (Irganox 1076) which were effective synergists during thermal oxidation of LDPE· were antagonistic during photo-oxidation. The mechanisms of these processes are discussed.

Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His7 and Ala8, can greatly improve resistance to this enzyme. Little research has assessed what effect Glu9-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu9 of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue (Lys9)GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys9)GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

A Differential Game Described by a Hyperbolic System

An antagonistic differential game of hyperbolic type with a separable linear vector pay-off function is considered. The main result is the description of all ε-Slater saddle points consisting of program strategies, program ε-Slater maximins and minimaxes for each ε ∈ R^N > for this game. To this purpose, the considered differential game is reduced to find the optimal program strategies of two multicriterial problems of hyperbolic type. The application of approximation enables us to relate these problems to a problem of optimal program control, described by a system of ordinary differential equations, with a scalar pay-off function. It is found that the result of this problem is not changed, if the players use positional or program strategies. For the considered differential game, it is interesting that the ε-Slater saddle points are not equivalent and there exist two ε-Slater saddle points for which the values of all components of the vector pay-off function at one of them are greater than the respective components of the other ε-saddle point.

Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom

The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

Cholecystokinin-1 receptor antagonists:5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents

A new class of 5-arylated 5-hydroxypyrrolones was derived from mucochloric acid in 2 synthetic steps and the chemical structure was confirmed additionally by X-ray analysis. Using a radiolabelled binding assay, potent CCK1 selective ligands were identified (CCK1: 12 nM) and the antagonism was confirmed by using isolated tissue preparations. A series of isobutyl derivatives displayed unsurmountable CCK antagonistic properties and in vitro excellent inhibition of proliferation was obtained in cholecystokinin related cancer cell lines in the nanomolar range. Finally, using xenograft studies in nude mice, two selected pyrrolone derivatives, X = H and X = F a fluorinated analogue (PNB-028), showed a strong inhibition of tumour growth in a chemo-resistant colon cancer-(MAC 16) and a human pancreatic cell line (MIAPACA) at 50 mg kg-1 by oral administration.

In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2- methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom

Objectives Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a 'snakebite antidote'. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom. Methods The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice. Key findings The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene] -succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 μg/ml venom, was reversed by 2-16 μg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group. Conclusions The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source. © 2010 Royal Pharmaceutical Society of Great Britain.

A mathematical resolution to log transformations and the binning effect in applied processing of data in flow cytometry

This dissertation develops a new mathematical approach that overcomes the effect of a data processing phenomenon known as “histogram binning” inherent to flow cytometry data. A real-time procedure is introduced to prove the effectiveness and fast implementation of such an approach on real-world data. The histogram binning effect is a dilemma posed by two seemingly antagonistic developments: (1) flow cytometry data in its histogram form is extended in its dynamic range to improve its analysis and interpretation, and (2) the inevitable dynamic range extension introduces an unwelcome side effect, the binning effect, which skews the statistics of the data, undermining as a consequence the accuracy of the analysis and the eventual interpretation of the data. ^ Researchers in the field contended with such a dilemma for many years, resorting either to hardware approaches that are rather costly with inherent calibration and noise effects; or have developed software techniques based on filtering the binning effect but without successfully preserving the statistical content of the original data. ^ The mathematical approach introduced in this dissertation is so appealing that a patent application has been filed. The contribution of this dissertation is an incremental scientific innovation based on a mathematical framework that will allow researchers in the field of flow cytometry to improve the interpretation of data knowing that its statistical meaning has been faithfully preserved for its optimized analysis. Furthermore, with the same mathematical foundation, proof of the origin of such an inherent artifact is provided. ^ These results are unique in that new mathematical derivations are established to define and solve the critical problem of the binning effect faced at the experimental assessment level, providing a data platform that preserves its statistical content. ^ In addition, a novel method for accumulating the log-transformed data was developed. This new method uses the properties of the transformation of statistical distributions to accumulate the output histogram in a non-integer and multi-channel fashion. Although the mathematics of this new mapping technique seem intricate, the concise nature of the derivations allow for an implementation procedure that lends itself to a real-time implementation using lookup tables, a task that is also introduced in this dissertation. ^

Hacia una poetica del Neobarroco: La vision de la historia en Jose Lezama Lima, Reinaldo Arenas y Severo Sarduy

Most of the critical studies of Baroque novels written in Spanish America during the 1960s and 1970s are characterized by a limited examination of their formal and stylistic representations. This dissertation explored the way in which certain writers developed a new Baroque tendency, the so-called Neobarroco, that presented a particular vision of history. José Lezama Lima, Reinaldo Arenas and Severo Sarduy developed innovative fictional and historiographic perceptions as alternative discourses to understand and perceive the cultural intricacies of Cuba and the New World. Their novels posited an elaborated poetic theory of history that can be summarized by the principle of supratemporal analogies, interweaved by a "metaphoric subject" that makes possible the conception of "imaginary eras". Since this poetry arises from a network of metaphoric correspondences, the image is conceived as a cultural creation that acts upon reality. ^ Although this study traced the trajectory of their writings from the point of view of their own essays, our focus was on the act of recovering the past as reshaped forms that are present in the memory. Paradiso, El mundo alucinante and De donde son los cantantes exemplified the attempt to place Americanness within the realm of poetics and history as one single discourse constructed by a combination of self-consciousness and historiographic meditation. ^ Basing my thesis on postmodernist theory (Ihab Hassan, Brian McHale, Linda Hutcheon) and philosophies of history (Michel Foucault, Hayden White, Keith Jenkins, Dominick LaCapra), I argued that the antagonistic paradoxes faced by postmodernism were reconcilable tendencies of the Neobarroco prior to the actual debate on the postmodern condition. The aesthetic trend initiated by these writers and their reading of history confronted the official historiographic discourse, thus empowering a contemporary voice in the current debate on historical skepticism. ^