New Philology and the Biogenetics of Texts

The discussion on the New Philology triggered by French and North American scholars in the last decade of the 20th century emphasized the material character of textual transmission inside and outside the written evidences of medieval manuscripts by downgrading the active role of the historical author. However, the reception of the ideas propagated by the New Philology adherents was rather divided. Some researchers considered it to be the result of an academic “crisis” (R.T. Pickens) or questioned its innovative status (K. Stackmann: “Neue Philologie?”); others appreciated the “new attitudes to the page” it had brought to mind (J. Bumke after R.H. and M.A, Rouse) or even saw a new era of the “powers of philology” evoked (H.-U. Gumbrecht). Besides the debates on the New Philology another concept of textual materiality strengthened in the last decade, maintaining that textual alterations somewhat relate to biogenetic mutations. In a matter of fact, phenomena such as genetic and textual variation, gene recombination and ‘contamination’ (the mixing of different exemplars in one manuscript text) share common features. The paper discusses to what extent the biogenetic concepts can be used for evaluating manifestations of textual production (as the approach of ‘critique génétique’ does) and of textual transmission (as the phylogenetic analysis of manuscript variation does). In this context yet the genealogical concept of stemmatology – the treelike representation of textual development abhorred by the New Philology adepts – might prove to be useful for describing the history of texts. The textual material to be analyzed will be drawn from the Parzival Project, which is currently preparing a new electronic edition of Wolfram von Eschenbach’s Parzival novel written shortly after 1200 and transmitted in numerous manuscripts up to the age of printing. Researches of the project have actually resulted in suggesting that the advanced knowledge of the manuscript transmission yields a more precise idea on the author’s own writing process.

The Transmission of Manuscripts and the Genetics of Texts. A new critical edition of Wolfram von Eschenbach’s Parzival

The discussion on the New Philology triggered by French and North American scholars in the last decade of the 20th century emphasized the material character of textual transmission inside and outside the written evidences of medieval manuscripts by downgrading the active role of the historical author. However, the reception of the ideas propagated by the New Philology adherents was rather divided. Some researchers questioned its innovative status (K. Stackmann: “Neue Philologie?”), others saw a new era of the “powers of philology” evoked (H.-U. Gumbrecht). Besides the debates on the New Philology another concept of textual materiality strengthened in the last decade, maintaining that textual alterations somewhat relate to biogenetic mutations. In a matter of fact, phenomena such as genetic and textual variation, gene recombination and ‘contamination’ (the mixing of different exemplars in one manuscript text) share common features. The paper discusses to what extent the biogenetic concepts can be used for evaluating manifestations of textual production (as the approach of ‘critique génétique’ does) and of textual transmission (as the phylogenetic analysis of manuscript variation does). In this context yet the genealogical concept of stemmatology – the treelike representation of textual development abhorred by the New Philology adepts – might prove to be useful for describing the history of texts. The textual material to be analyzed will be drawn from the Parzival Project, which is currently preparing a new electronic edition of Wolfram von Eschenbach’s Parzival novel written shortly after 1200 and transmitted in numerous manuscripts up to the age of printing (www.parzival.unibe.ch). Researches of the project have actually resulted in suggesting that the advanced knowledge of the manuscript transmission yields a more precise idea on the author’s own writing process.

Nonthymoma-associated exfoliative dermatitis in 18 cats.

BACKGROUND Exfoliative dermatitis has been described in cats as a paraneoplastic skin disease associated with thymoma. There are anecdotal reports of cases without thymoma, with various suspected aetiologies. HYPOTHESIS/OBJECTIVES To identify common features, underlying causes, response to therapy and outcome of nonthymoma-associated exfoliative dermatitis in cats. METHODS Retrospective analysis was carried out of cases presented to dermatology referral centres or cases submitted for histopathological examination. Detailed historical and clinical data were obtained and evaluated statistically. Histopathology was reviewed in a blinded fashion by three dermatopathologists, and PCR for herpesvirus was performed. RESULTS Eighteen cats fulfilled all inclusion criteria. There was no sex, age or breed predisposition. All cats presented with severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely depressed. In all cats, thymoma was excluded radiographically and feline leukaemia virus tests were negative. Additional imaging procedures in 14 cats and postmortem examination in two cats did not detect neoplasia. Histopathology revealed interface dermatitis, mural interface folliculitis and sebaceous adenitis indistinguishable from findings in thymoma-associated cases. PCR for herpes DNA was negative. No aetiology was identified. Treatment in 12 cases consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one responded to antibiotics, one to shampoo, two went into spontaneous remission, and two did not receive any therapy and were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE Nonthymoma-associated exfoliative dermatitis in cats is clinically and histopathologically indistinguishable from thymoma-associated cases. Most cases benefit from immunosuppressive therapy; therefore, an immunopathological response to an undefined trigger is suspected.

Transcriptional regulation of tenascin genes

Extracellular matrix proteins of the tenascin family resemble each other in their domain structure, and also share functions in modulating cell adhesion and cellular responses to growth factors. Despite these common features, the 4 vertebrate tenascins exhibit vastly different expression patterns. Tenascin-R is specific to the central nervous system. Tenascin-C is an "oncofetal" protein controlled by many stimuli (growth factors, cytokines, mechanical stress), but with restricted occurrence in space and time. In contrast, tenascin-X is a constituitive component of connective tissues, and its level is barely affected by external factors. Finally, the expression of tenascin-W is similar to that of tenascin-C but even more limited. In accordance with their highly regulated expression, the promoters of the tenascin-C and -W genes contain TATA boxes, whereas those of the other 2 tenascins do not. This article summarizes what is currently known about the complex transcriptional regulation of the 4 tenascin genes in development and disease.

Ovarian cancer angiogenesis, biology and therapy

The progressive growth of epithelial ovarian cancer tumor is regulated by proangiogenic molecules and growth factors released by tumor cells and the microenvironment. Previous studies showed that the expression of interleukin-8 (IL-8) directly correlates with the progression of human ovarian carcinomas implanted into the peritoneal cavity of nude mice. We examined the expression level of IL-8 in archival specimens of primary human ovarian carcinoma from patients undergoing curative surgery by in situ mRNA hybridization technique. The expression of IL-8 was significantly higher in patients with stage III disease than in patients with stage I disease. To investigate the role of IL-8 in the progressive growth of ovarian cancer, we isolated high- and low-IL-8 producing clones from parental Hey-A8 human ovarian cancer cells, and compared their proliferative activity and tumorigenicity in nude mice. The effect of exogenous IL-8 and IL-8 neutralizing antibody on ovarian cancer cell proliferation was investigated. Finally, we studied the modulation of IL-8 expression in ovarian cancer cells by sense and antisense IL-8 expression vector transfection and its effect on proliferation and tumorigenicity. We concluded that IL-8 has a direct growth potentiating activity in human ovarian cancer cells. ^ The expression level of IL-8 directly correlates with disease progression of human ovarian cancer, but the mechanism of induction is unknown. Since hypoxia and acidic pH are common features in solid tumors, we determined whether hypoxic and acidic conditions could regulate the expression of IL-8. Culturing the human ovarian cancer cells in hypoxic or acidic medium led to a significant increase in IL-8 mRNA and protein. Hypoxic- and acidosis-mediated transient increase in IL-8 expression involved both transcriptional activation of the IL-8 gene and enhanced stability of the IL-8 mRNA. Furthermore, we showed that IL-8 transcription activation by hypoxia or acidosis required the cooperation of NF-κB and AP-1 binding sites. ^ Finally, we studied novel therapies against human ovarian cancer. First, we determined whether inhibition of the catalytic tyrosine kinase activity of the receptors for vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) inhibits the formation of malignant ascites and the progressive growth of human ovarian carcinoma cells implanted into the peritoneal cavity of nude mice. Our results suggest that blockade of the VEGF/VPF receptor may be an efficient strategy to inhibit formation of malignant ascites and growth of VEGF/VPF-dependent human ovarian carcinomas. Secondly, we determined whether local sustained production of murine interferon-β could inhibit the growth of human ovarian cancer cells in the peritoneal cavity of nude mice. Our results showed that local production of IFN-β could inhibit the in vivo growth of human ovarian cancer cells by upregulating the expression of the inducible nitric oxide synthase (NOS) in host macrophages. ^

The medical malpractice insurance "crises" and federal medical malpractice tort reform: Collection and analysis of bills passed by the United States House of Representatives from 1995--2005

There have been three medical malpractice insurance "crises" in the United States over a time spanning roughly the past three decades (Poisson, 2004, p. 759-760). Each crisis is characterized by a number of common features, including rapidly increasing medical malpractice insurance premiums, cancellation of existing insurance policies, and a decreased willingness of insurers to offer or renew medical malpractice insurance policies (Poisson, 2004, p. 759-760). Given the recurrent "crises," many sources argue that medical malpractice insurance coverage has become too expensive a commodity—one that many physicians simply cannot afford (U.S. Department of Health and Human Services [HHS], 2002, p. 1-2; Physician Insurers Association of America [PIAA], 2003, p. 1; Jackiw, 2004, p. 506; Glassman, 2004, p. 417; Padget, 2003, p. 216). ^ The prohibitively high cost of medical liability insurance is said to limit the geographical areas and medical specializations in which physicians are willing to practice. As a result, the high costs of medical liability insurance are ultimately said to affect whether or not people have access to health care services. ^ In an effort to control the medical liability insurance crises—and to preserve or restore peoples' access to health care—every state in the United States has passed "at least some laws designed to reduce medical malpractice premium rates" (GAO, 2003, p.5-6). More recently, however, the United States has witnessed a push to implement federal reform of the medical malpractice tort system. Accordingly, this project focuses on federal medical malpractice tort reform. This project was designed to investigate the following specific question: Do the federal medical malpractice tort reform bills which passed in the House of Representatives between 1995 and 2005 differ in respect to their principle features? To answer this question, the text of the bills, law review articles, and reports from government and private agencies were analyzed. Further, a matrix was compiled to concisely summarize the principle features of the proposed federal medical malpractice tort reform bills. Insight gleaned from this investigation and matrix compilation informs discussion about the potential ramifications of enacting federal medical malpractice tort reform legislation. ^

Mitochondrial dysfunction leads to NOX activation: A novel mechanism to maintain high glycolysis in cancer cells

Increased glycolysis and oxidative stress are common features of cancer cells. These metabolic alterations are associated with mitochondrial dysfunction and can be caused by mitochondrial DNA (mtDNA) mutations, oncogenic signals, loss of tumor suppressor, and tumor tissue hypoxia. It is well established that mitochondria play central roles in energy metabolism, maintenance of redox balance, and regulation of apoptosis. However, the biochemical and molecular mechanisms that maintain high glycolysis in cancer cells (the Warburg effect) with mitochondrial dysfunction and oxidative stress remain to be determined. The major goals of this study were to establish a unique experimental system in which the mitochondrial respiratory function can be regulated as desired, and to use this system to investigate the mechanistic link between mitochondrial dysfunction and the Warburg effect along with oxidative stress in cancer cells. To achieve these goals, I have established a tetracycline-inducible system in which a dominant negative form of mitochondrial DNA polymerase y (POLGdn) expression could be regulated by tetracycline; thus controlling mitochondrial respiratory function. Using this cell system, I demonstrated that POLGdn expression resulted in mitochondrial dysfunction through decreasing mtDNA content, depletion of mtDNA encoded mRNA and protein expression. This process was mediated by TFAM proteasome degradation. Mitochondrial dysfunction mediated by POLGdn expression led to a significant increase in cellular glycolysis and oxidative stress. Surprisingly, mitochondrial dysfunction also resulted in increased NAD(P)H oxidase (NOX) enzyme activity, which was shown to be essential for maintaining high glycolysis. Chemical Inhibition of NOX activity by diphenyliodonium (DPI) preferentially impacted the survival of mitochondrial defective cells. The colon cancer HCT116-/- cells that have lost transcriptional regulation of the mitochondrial assembling enzyme SCO2, leading to compromised mitochondrial respiratory function, were found to have increased NOX activity and were highly sensitive to DPI treatment. Ovarian epithelial cells with Ras transformation also exhibited an increase in NOX gene expression and NOX enzyme activity, rendering the cells sensitive to DPI inhibition especially under hypoxic condition. These data together suggest that NOX plays a novel role in maintaining high glycolysis in cancer cells with mitochondrial defects, and that NOX may be a potential target for cancer therapy. ^

Water stable oxygen isotope records from six Antarctic ice core sites for the present and last interglacial periods

We compare the present and last interglacial periods as recorded in Antarctic water stable isotope records now available at various temporal resolutions from six East Antarctic ice cores: Vostok, Taylor Dome, EPICA Dome C (EDC), EPICA Dronning Maud Land (EDML), Dome Fuji and the recent TALDICE ice core from Talos Dome. We first review the different modern site characteristics in terms of ice flow, meteorological conditions, precipitation intermittency and moisture origin, as depicted by meteorological data, atmospheric reanalyses and Lagrangian moisture source diagnostics. These different factors can indeed alter the relationships between temperature and water stable isotopes. Using five records with sufficient resolution on the EDC3 age scale, common features are quantified through principal component analyses. Consistent with instrumental records and atmospheric model results, the ice core data depict rather coherent and homogenous patterns in East Antarctica during the last two interglacials. Across the East Antarctic plateau, regional differences, with respect to the common East Antarctic signal, appear to have similar patterns during the current and last interglacials. We identify two abrupt shifts in isotopic records during the glacial inception at TALDICE and EDML, likely caused by regional sea ice expansion. These regional differences are discussed in terms of moisture origin and in terms of past changes in local elevation histories, which are compared to ice sheet model results. Our results suggest that elevation changes may contribute significantly to inter-site differences. These elevation changes may be underestimated by current ice sheet models

Paleoproductivity reconstruction for the eastern equatorial Pacific

Productivity at six core locations in the eastern equatorial Pacific (EEP) was reconstructed with a benthic foraminiferal transfer function. The core records show strong regionality, especially where affected by Peru margin upwelling of deeper Equatorial Undercurrent Water (EUC) (originally coming from the subantarctic). This "Peru margin" record differs from that seen along the equator where divergence leads to shallow upwelling, and it is generally inverse to that seen in cores outside the areas of equatorial upwelling. Principal components analysis shows that the main productivity pattern correlates well to the global oxygen isotope record and has lowest values during isotope stages 2 and 4. In addition to this, equatorial cores show a higher frequency pattern of variation which becomes much more pronounced during MIS 3 and 2. The reconstructions based on benthic foraminifera were tested against those from nonaccumulation rate based inorganic chemical proxies of export production. These were found to correlate well in the region influenced by Peru upwelling, and also to share common features for sites along the equator. All the nonaccumulation rate based paleotracers are consistent with one another and differ from accumulation rate derived proxies. The differences between the two classes of paleotracers may result from uncertainties in calculating actual biogenic fluxes since 230Th-normalized results conform more to those we obtained. Analysis of planktonic carbon isotope values for the EEP, and their comparison to the record of the Pacific subantarctic, indicates that the subantarctic contribution to the EUC was reduced during MIS 3 and 2.

Principales problemáticas y potencialidades de la región nordeste

El presente trabajo enfoca la región del Nordeste Argentino como un conjunto de provincias que presentan una realidad compleja, distinguidas por una serie de rasgos comunes que las unifican como región y permiten examinar sus principales problemáticas y potencialidades. El análisis selecciona y jerarquiza ciertos aspectos de la cuestión, de modo de brindar una perspectiva centrada en los aspectos estratégicos para el desarrollo regional

Representaciones de la transición española en la novela actual : Una indagación en la configuración de la cultura democrática

La noción de la transición como "matriz" de nuestro tiempo presente, como mito fundador de la España contemporánea es, hoy, uno de los puntos fundamentales de los debates culturales más recientes de nuestro país. Si consideramos el proceso de cambio político de la transición a la democracia como el punto de partida del proyecto democrático español aún vigente, el surgimiento de una serie de novelas centradas en el mismo resulta tan sintomático como oportuno. Por ello, en este artículo tratamos de interrogar las condiciones en las que ha aparecido esta serie de novelas, sus presupuestos comunes y los distintos núcleos de discusión a los que apuntan. Desde el análisis de la producción de una serie de autores nacidos entre la década de los sesenta y los setenta, y en concreto de la novela El jardín colgante (2012) esbozaremos, a grandes rasgos, la problemática generacional que la vuelta al debate sobre la transición supone en el contexto de la España contemporánea.

Principales problemáticas y potencialidades de la región nordeste

El presente trabajo enfoca la región del Nordeste Argentino como un conjunto de provincias que presentan una realidad compleja, distinguidas por una serie de rasgos comunes que las unifican como región y permiten examinar sus principales problemáticas y potencialidades. El análisis selecciona y jerarquiza ciertos aspectos de la cuestión, de modo de brindar una perspectiva centrada en los aspectos estratégicos para el desarrollo regional

Representaciones de la transición española en la novela actual : una indagación en la configuración de la cultura democrática

La noción de la transición como "matriz" de nuestro tiempo presente, como mito fundador de la España contemporánea es, hoy, uno de los puntos fundamentales de los debates culturales más recientes de nuestro país. Si consideramos el proceso de cambio político de la transición a la democracia como el punto de partida del proyecto democrático español aún vigente, el surgimiento de una serie de novelas centradas en el mismo resulta tan sintomático como oportuno. Por ello, en este artículo tratamos de interrogar las condiciones en las que ha aparecido esta serie de novelas, sus presupuestos comunes y los distintos núcleos de discusión a los que apuntan. Desde el análisis de la producción de una serie de autores nacidos entre la década de los sesenta y los setenta, y en concreto de la novela El jardín colgante (2012) esbozaremos, a grandes rasgos, la problemática generacional que la vuelta al debate sobre la transición supone en el contexto de la España contemporánea.

Climate proxies in sediment core MD95-2010

High-amplitude, rapid climate fluctuations are common features of glacial times. The prominent changes in air temperature recorded in the Greenland ice cores (Dansgaard et al., 1993, doi:10.1038/339532a0; Grootes et al., 1993 doi:10.1038/366552a0) are coherent with shifts in the magnitude of the northward heat flux carried by the North Atlantic surface ocean (Bond et al., 1993, doi:10.1038/365143a0; Bond and Lotti, 1995, doi:10.1126/science.267.5200.1005); changes in the ocean's thermohaline circulation are a key component in many explanations of this climate flickering (Broecker, 1997, doi:10.1126/science.278.5343.1582). Here we use stable-isotope and other sedimentological data to reveal specific oceanic reorganizations during these rapid climate-change events. Deep water was generated more or less continuously in the Nordic Seas during the latter part of the last glacial period (60 to 10 thousand years ago), but by two different mechanisms. The deep-water formation occurred by convection in the open ocean during warmer periods (interstadials). But during colder phases (stadials), a freshening of the surface ocean reduced or stopped open-ocean convection, and deep-water formation was instead driven by brine-release during sea-ice freezing. These shifting magnitudes and modes nested within the overall continuity of deep-water formation were probably important for the structuring and rapidity of the prevailing climate changes.

Principales problemáticas y potencialidades de la región nordeste

El presente trabajo enfoca la región del Nordeste Argentino como un conjunto de provincias que presentan una realidad compleja, distinguidas por una serie de rasgos comunes que las unifican como región y permiten examinar sus principales problemáticas y potencialidades. El análisis selecciona y jerarquiza ciertos aspectos de la cuestión, de modo de brindar una perspectiva centrada en los aspectos estratégicos para el desarrollo regional