bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proapoptotic Bcl-2 Family Member Bim Promotes Persistent Infection and Limits Protective Immunity
Authors: Reckling Stacie , Divanovic Senad , Karp Christopher L. , Wojciechowski Sara , Belkaid Yasmine , Hildeman David 
Published: December 2007

ABSTRACTFollowing the peak of the T-cell response, most of the activated effector T cells die by apoptosis driven by the proapoptotic Bcl-2 family member Bim (Bcl-2-interactingmediator of death). Whether the absence of Bim-mediated T-cell apoptosis can affect protective immunity remains unclear. Here, we used a mouse model ofLeishmania majorinfection, in which parasite persistence and protective immunity are controlled by an equilibrium reached between parasite-specific gamma interferon (IFN-γ)-producing effector T cells and interleukin-10 (IL-10)-producing CD4+CD25+T regulatory cells. To further understand the role of Bim-mediated apoptosis in persistent infection and protective immunity, we infectedBim−/−mice withL. major. We found that the initial parasite growth and lesion development were similar inBim−/−and wild-type mice after primaryL. majorinfection. However, at later times after infection,Bim−/−mice had significantly increasedL. major-specific CD4+T-cell responses and were resistant to persistent infection. Interestingly, despite their resistance to primaryL. majorinfection,Bim−/−mice displayed significantly enhanced protection against challenge withL. major. Increased resistance to challenge inBim−/−mice was associated with a significant increase in the number ofL. major-specific IFN-γ-producing CD4+T cells and a lack of IL-10 production at the challenge site. Taken together, these data suggest that Bim limits protective immunity and that the absence of Bim allows the host to bypass antigen persistence for maintenance of immunity against reinfection.
Landslide hazard mapping and risk assessment
Authors: Hearn G. J. , Griffiths J. S. 
Published: December 2007

Definitions
Before landslide hazard mapping and risk assessment are reviewed, it is important to define terms and concepts closely in order to avoid the confusion and misuse that has occurred in some previously reported case histories. The most widely accepted and basic definitions in landslide studies are those provided by Varnes (1984).

Natural Hazard:
the probability of occurrence within a specified period of time and within a given area of a potentially damaging phenomenon.

Vulnerability:
the degree of loss to a given element or set of elements resulting from the occurrence of a natural phenomenon of a given magnitude. It is expressed on a scale from 0 (no damage) to 1 (total loss).

Specific Risk:
the expected degree of loss due to a particular natural phenomenon. It may be expressed by the product of
Hazard
and
Vulnerability
.

Elements at Risk:
the population, properties, economic activities, including public services, etc., at risk in a given area.

Total Risk:
the expected number of lives lost, persons injured, damage to property or disruption of economic activity due to a particular natural phenomenon. It is therefore the product of
Specific Risk
and
Elements at Risk
.

These definitions have been expanded by the International Union of Geological Sciences (IUGS) Working Party on Landslides through its committee on Risk Assessment (IUGS 1997) but the main elements are essentially the same.

Hazard,
therefore, defines the
potential to cause damage
. With respect to landslides it is necessary to: identify the existence of a landslide or a potential slope failure; establish its size, depth, speed and travel distance; and estimate or calculate its frequency of movement or its probability of occurrence.
Hsp27 Modulates p53 Signaling and Suppresses Cellular Senescence
Authors: O'Callaghan-Sunol Cornelia , Gabai Vladimir L. , Sherman Michael Y. 
Published: December 2007

Abstract
The small heat shock protein Hsp27 is expressed at high levels in many tumors and provides protection against anticancer drugs. Here, we show that expression of recombinant Hsp27 at elevated levels leads to protection of MCF10A human mammary epithelial cells from doxorubicin. The protection was associated with suppression of the doxorubicin-induced senescence, where Hsp27 inhibited p53-mediated induction of p21, the major regulator of the senescence program. Similarly, Hsp27 inhibited accumulation of p21 and suppressed senescence in response to the p53 activator nutlin-3, indicating that Hsp27 has a general effect on the p53 pathway. In line with these findings, down-regulation of Hsp27 in HCT116 human colon carcinoma cells that express this heat shock protein at high levels caused senescence in a population of cells and sensitized the rest of the cells to doxorubicin-induced senescence (at low doses) or apoptosis (at high doses of doxorubicin). Induction of senescence by Hsp27 down-regulation associated with activation of the p53 pathway and induction of p21. Interestingly, depletion of Hsp27 caused neither significant proteotoxic nor genotoxic stress, and therefore this heat shock protein seems to have a specific effect on the p53 signaling. Indeed, Hsp27 down-regulation was associated with destabilization of HDM2 and stabilization of p53. These data suggest that Hsp27 may play a general role in regulation of cellular senescence by modulating the p53 pathway. [Cancer Res 2007;67(24):11779–88]
Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis
Authors: Loehberg Christian R. , Thompson Tiia , Kastan Michael B. , Maclean Kirsteen H. , Edwards Dean G. , Kittrell Frances S. , Medina Daniel , Conneely Orla M. , O'Malley Bert W. 
Published: December 2007

Abstract
The use of agents to prevent the onset of and/or the progression to breast cancer has the potential to lower breast cancer risk. We have previously shown that the tumor-suppressor gene p53 is a potential mediator of hormone (estrogen/progesterone)-induced protection against chemical carcinogen–induced mammary carcinogenesis in animal models. Here, we show for the first time a breast cancer–protective effect of chloroquine in an animal model. Chloroquine significantly reduced the incidence of N-methyl-N-nitrosourea–induced mammary tumors in our animal model similar to estrogen/progesterone treatment. No protection was seen in our BALB/c p53-null mammary epithelium model, indicating a p53 dependency for the chloroquine effect. Using a human nontumorigenic mammary gland epithelial cell line, MCF10A, we confirm that in the absence of detectable DNA damage, chloroquine activates the tumor-suppressor p53 and the p53 downstream target gene p21, resulting in G1 cell cycle arrest. p53 activation occurs at a posttranslational level via chloroquine-dependent phosphorylation of the checkpoint protein kinase, ataxia telangiectasia-mutated (ATM), leading to ATM-dependent phosphorylation of p53. In primary mammary gland epithelial cells isolated from p53-null mice, chloroquine does not induce G1 cell cycle arrest compared with cells isolated from wild-type mice, also indicating a p53 dependency. Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis. [Cancer Res 2007;67(24):12026–33]
Cell type–dependent effects of Polo-like kinase 1 inhibition compared with targeted polo box interference in cancer cell lines
Authors: Fink Jenny , Sanders Karl , Rippl Alexandra , Finkernagel Sylvia , Beckers Thomas L. , Schmidt Mathias 
Published: December 2007

Abstract
Multiple critical roles within mitosis have been assigned to Polo-like kinase 1 (Plk1), making it an attractive candidate for mitotic targeting of cancer cells. Plk1 contains two domains amenable for targeted interference: a kinase domain responsible for the enzymatic function and a polo box domain necessary for substrate recognition and subcellular localization. Here, we compare two approaches for targeted interference with Plk1 function, either by a Plk1 small-molecule enzyme inhibitor or by inducible overexpression of the polo box in human cancer cell lines. Inducible expression of the Plk1 polo box resulted in growth inhibition of RKOp27 human colon adenocarcinoma cells without obvious signs of mitotic abnormalities. A Plk1 kinase inhibitor in the same cell line arrested cells in mitosis with subsequent onset of apoptosis. Similarly, PC-3 human prostate cancer cells were growth inhibited on expression of the polo box. Prolonged expression of the polo box in these cells resulted in the occurrence of binucleated or multinucleated cells. In contrast, U2OS human osteosarcoma cells responded to overexpression of the polo box with a massive mitotic accumulation coinciding with the onset of apoptosis. Comparison of spindle formation revealed very similar mitotic abnormalities in polo box–overexpressing U2OS cells compared with U2OS cells treated with the Plk1 kinase inhibitor. We conclude that interference with polo box function and inhibition of Plk1 kinase activity can exert very similar phenotypic effects in certain cell lines but highly contrasting effects in others. This may point to subtle differences in the molecular machinery of mitosis regulation in cancer cells. [Mol Cancer Ther 2007;6(12):3189–97]
Chemical synthesis and biological evaluation of a NAD(P)H:quinone oxidoreductase-1–targeted tripartite quinone drug delivery system
Authors: Volpato Milène , Abou-Zeid Nathalie , Tanner Richard W. , Glassbrook Lee T. , Taylor James , Stratford Ian , Loadman Paul M. , Jaffar Mohammed , Phillips Roger M. 
Published: December 2007

Abstract
NAD(P)H:quinone oxidoreductase-1 (NQO1) is a potential target for therapeutic intervention but attempts to exploit NQO1 using quinone-based bioreductive prodrugs have been largely compromised by toxicity to organs that inherently express high levels of NQO1. In an attempt to circumvent this problem, this study describes the development of a tripartite quinone-based drug delivery system, the ultimate objective of which is to release a targeted therapeutic agent following the reduction of a quinone “trigger” by NQO1. Molecular modeling of drug/NQO1 interactions were conducted prior to the synthesis of N-{4-[bis-(2-chloroethyl)-amino]-phenyl}-β,β,2,4,5-pentamethyl-3,6-dioxo-1,4-cyclohexadiene-1-propanamide (prodrug 1). Prodrug 1 is a good substrate for purified NQO1 (Vmax and Km values of 11.86 ± 3.09 μmol/min/mg and 2.70 ± 1.14 μmol/L, respectively) and liquid chromatography-mass spectrometry analysis of the metabolites generated showed that lactone 3 and aniline mustard 4 were generated in a time- and NQO1-dependent manner. Chemosensitivity studies showed that prodrug 1 is selectively toxic to cells that overexpress NQO1 under aerobic conditions, and comet assay analysis confirmed the presence of elevated interstrand cross-links in NQO1-rich compared with NQO1-deficient cells. Hypoxic sensitization (hypoxic cytotoxicity ratio = 15.8) was observed in T47D cells that overexpress cytochrome P450 reductase. In conclusion, the results of this study provide mechanistic proof of principle that a tripartite benzoquinone drug delivery system is enzymatically reduced to release an active therapeutic agent. Further development of this concept to fine-tune substrate specificity for specific reductases and/or the inclusion of alternative therapeutic agents is warranted. [Mol Cancer Ther 2007;6(12):3122–30]
La Beata Laura Vicuña: The Nun's Version, Corrective of García Márquez's
Authors: Cussen John 
Published: December 2007

AbstractThis paper identifies América Vicuña, the name given to the ill-used Lolita of García Márquez's Love in the Time of Cholera, as a reference to Laura Vicuña (1891–1904), a turn-of-the-century Chilean teen declared venerable (the sainthood process's third-to-last step) by Pope John Paul II in the same year as Cholera's publication (1985). About the author, the allusion's identification reveals these facts: his continued animus against the Catholic Church, in particular, the pique raised in him by the Church's sexual ethics; also, the allusion points up the centrality and durability of the issue of desire's burden in the shelf of his work, as well as the likelihood that his focus on this issue diverts his otherwise remarkable vision. As regards the book, the allusion's pursuit calls into question the América Vicuña episode's most circulated interpretation, wherein América's lethal affection for her grand relative, the Old World's arch-romantic, and the old man's exploitation of that affection are thought to represent the "destruction which over the centuries has been wreaked on the (female) body of America by various predators, domestic and foreign alike" (Fiddian). To the contrary, in the allusion's light it is clear that América is neither charmed nor exploited by the Old World's courtly deceptions. Instead, her spontaneous sexual behavior bespeaks the author's effort to wreck inherited literary notions of female sexual discretion, just as the same behavior, with a saint's name pinned to it, bespeaks his intention to mock the Church's chastity ethic.Lastly, the paper argues that García Márquez's understanding of the Laura Vicuña history as a death-rather-than-sex parable is regrettably narrow. Focused on the Church's sexual ethics, he fails to see that her story is also about caste and about the struggle between civilization and barbarism on the nineteenth-century Latin American frontier; about female self-determination, and about a woman's right to keep and/or share her body as she sees fit. In short, the story is about themes handled by works descriptive of her proximate historic reality, among them, Orrego Luco's Casa Grande, Sarmiento's Facundo, Jorge Icaza's Huasipungo, Allende's House of the Spirits.
Materialist Criticism and Cordelia's Quasi-Resurrection in King Lear
Authors: Benson Sean 
Published: December 2007

AbstractThis essay examines King Lear's belief that the dead Cordelia revives or resuscitates near the very end of the play. This quasi-resurrection, which occurs only in the First Folio (1623), has divided critics into those who regard the moment as mere delusion and others who see it as adumbrating a moment of blessed release. Following a survey of these "redemptionist" versus the predominant nihilist-oriented readings of the play, I examine the influential materialist interpretations offered by Stephen Greenblatt and Jonathan Dollimore. Both insist that Cordelia's quasi-resurrection, since it never reaches fruition, frustrates a religious understanding of the play. (Materialist criticism only counts tangible rewards as meaningful.) The play, however, is more consistent with Hans-Georg Gadamer's view that tragedy overwhelms us with its suffering rather than promotes this-worldly justice. Cordelia's quasi-resurrection gestures towards a possible otherworldly redemption even as it reminds audiences of the Resurrection that, in Lear's pagan world, cannot be replicated. Shakespeare's anachronisms thus superimpose the Christian resurrectionary tradition on the pagan setting of the play; his doing so places the hope and despair of the final scene—the contrast between their transcendent aspirations and the mundane reality of their unresurrected corpses—in the delicate equipoise of his art.
De otio religioso: Petrarch and the Laicization of Western Monastic Asceticism
Authors: Yocum Demetrio 
Published: December 2007

AbstractThree of Petrarch's major prose works in Latin—De otio religioso, De vita solitaria, and Secretum—are treatises dedicated to the topic of solitude as an escape from the negotium of worldly life. An inquiry into Petrarch's understanding of solitude will show, however, that far from representing an idealized withdrawal from engagement in the world, ascesis is a technique employed by Petrarch to construct his own ideal of the public intellectual, disengaged and resistant to structures of coercive authority and power. His reshaping of an ascetic lineage, which puts early Christian authors side by side with writers from the ancient Latin Stoic tradition, may be seen as an attempt to delineate a new, laicized form of monasticism and the ascetic life. In turning to a closer examination of De otio religioso, this paper will emphasize two areas of interest, which seek to support the thesis that Petrarch's pursuit of contemplative life was strategic for the shaping of an uncompromised, intellectual, Christian identity: the presence of an absence, represented by Bruno, founder of the Carthusian order, as a model of ascetic dissent; and the absence of a presence, evoked by a radical reading of the Latin verb vacare with its more kenotic implications.
Hot Meetings and Hard Kraals: African Biblewomen in Transvaal Methodism, 1924-601
Authors: Gaitskell Deborah 
Published: December 2007

AbstractWhereas women's prayer groups are a well-known strength of African Christianity in Southern Africa, the evangelistic and pastoral contribution of individual women who were not clergy wives has been under-appreciated. Echoing models from Victorian London and Indian missions, Methodism in South Africa evolved an authorised, paid form of female lay ministry via middle-aged black Biblewomen sponsored and overseen by white Women's Auxiliary groups. The first appointee in the Transvaal and Swaziland District wrote comparatively full reports of emotionally 'hot' revival meetings. In 'hard' kraals she encountered hostility in the form of patriarchal control of women and an unusual proliferation of rival indigenous spirits. Her successors found male drinking an even greater obstacle to a sympathetic hearing. In urban townships along the Witwatersrand, Biblewomen work was less pioneering and more routinised, providing pastoral support to local churches via sick-visiting and following up lapsed members. From 1945-59, some Biblewomen were trained at Lovedale Bible School. The period after 1960 deserves separate exploration. In 1997, a new start was made with a national, autonomous Biblcwomen ministry, though many women, black and white, regretted severing their personal and organisational links of mutual dependence.
Growth and Decline in South Africa's Churches, 1960-911
Authors: Goodhew David 
Published: December 2007

AbstractSouth Africa's churches grew or declined so quickly in the years after 1960 that by 1991 the country's religious map had been redrawn. This article charts and offers explanations for such developments. Almost all Christian churches grew substantially in the first half of the twentieth century but mainline churches were dominant. They continued to grow numerically into the 1960s and 1970s, but were beginning to shrink as a proportion of the expanding population. By contrast, Roman Catholic, African Independent and smaller independent denominations were growing quickly. By the 1990s, mainline Protestant churches were suffering considerable decline and Roman Catholicism's growth had stalled. African Independent and other churches continued to grow rapidly. A matrix of forces help to explain this phenomenon-including the political situation, socio-economic pressures, secularisation and particular religious factors. A comparative perspective shows South Africa's churches to have much in common with African and global trends.
Harmis Al-Harāmisa Dans L'Alchimie Islamique. Une Recherche Par Auteur Et Par Sujet
Authors: Carusi Paola 
Published: December 2007

AbstractTenth-century Islamic alchemy attributed different roles to the figure of Hermes, all of which were retained in later alchemy. The playful changing of perspectives, in which Harmis al-Harāmisa perpetually changed his connotation, allowed for a complex game played at the border between science and literature. In the process, he turned from representing the venerable author of the early alchemical texts - master over ancient wisdom and scientific 'subject' - into an 'object' of research, into an allegory of the nucleus of the Great Work, and into a mysterious image of the secret that he himself had handed over to men.
Augurello's Chrysopoeia (1515)-a Turning Point in the Literary Tradition of Alchemical Texts1
Authors: Von Martels Zweder 
Published: December 2007

AbstractIn this article, new important instances of the favourable reception of Augurello's Chrysopoeia (1515) are discussed: a) the 21 editions of the poem, but especially the 1518 edition of Froben, and the Chrysopoeiae compendium paraphrasticum of 1614; b) the marginal notes of Aegidius de Vadis, Giulio Camillo Delminio, and an anonymous author in (manuscript) copies of Augurello's work; c) Henricus Cornelius Agrippa, De incertitudine et vanitate scientiarum declamatio inuectiua (1531), chapter XC on alchemy; and finally d) Ioannes Agrippa, Vellus aureum (1560). It is shown that the Chrysopoeia was read on account of both its contents and elegant language and style. This fortunate combination explains the 'classical' status the poem has acquired within alchemical literature.
Galileo and Pisan Aristotelianism: Galileo's De Motu Antiquiora and the Quaestiones De Motu Elementorum of the Pisan Professors
Authors: Helbing Mario , Camerota Michele 
Published: December 2007

AbstractThe group of writings entitled De motu (or De motu antiquiora) constitutes Galileo's earliest writings on dynamics. These manuscripts are usually dated to the years 1589 to 1592, when Galileo taught mathematics at the University of Pisa. Among their characteristics, the application of dynamic principles of Archimedean hydrostatics to the problem of motion stands out, as does their anti-Aristotelian tone. This paper tries to embed these writings within the cultural context in which they were created by documenting their link (which is most evident in various polemically charged references) to the debate over the motion of the elements between Girolamo Borro and Francesco Buonamici, the two most celebrated Pisan Aristotelians of the late sixteenth century.
Morbus-Locke's Early Essay On Disease
Authors: Walmsley Jonathan 
Published: December 2007

AbstractJohn Locke engaged in a systematic study of medicine from the late 1650's. In this period he acquainted himself with the three main competing natural philosophical theories of the time-Galenism, Paracelsianism and Mechanism. He was particularly interested in the work of Sennert, Helmont and Boyle. In 1666, just after the publication of Boyle's The Origine of Formes and Qualities, Locke wrote a short paper entitled Morbus. This paper gave Locke's own view of the nature of disease. Locke went out of his way to criticise Boyle's attempts to give mechanical explanations for biological phenomena. He endorsed Helmont's theory that disease was caused by "ferments" and "Archei" and re-introduced Galenic temperaments as factors of susceptibility in seminal diseases. Locke did not endorse a mechanical corpuscularianism at this stage in his career, when his contact with Boyle was most frequent. Consequently, Locke's espousal of the corpuscular philosophy in the Essay cannot be attributed to Locke's association with Boyle at this time.
The University of Leiden-an Eclectic Institution
Authors: Otterspeer Willem 
Published: December 2007

AbstractLeiden University was founded in 1575, not only in the midst of great political turmoil, but also in a time that experimented intensely with new forms of higher education. In due course Leiden was to choose an eclectic attitude, remaining loyal on the one hand to late medieval, scholastic traditions, but on the other hand emancipating the arts faculty in agreement with humanist ideas. The thesis this article wants to examine is that the curriculum of Leiden University during the first 75 years of its existence was characterised by a high level of pre-university, Latin schooling, and, linked up with this, a differentiation and specialisation of the arts faculty. These developments, however, had social rather than scientific goals. The arts courses did not prepare the way for a well-defined profession, but served as an initiation into a cultural élite.