bluuebunny/crossref_metadata_2025_split huggingface dataset:
2 Plan of the Book
Authors: Ott Walter 
Published: September 2009

AbstractThis short chapter sets out the chapters within the parts that follow. Part I sketches the Cartesian predicament. Having broken with the scholastics on key issues in ontology, Descartes faces a central tension. On one hand, he is clearly optimistic about the ability of mechanism to provide perspicuous explanations of body–body causation. On the other, he gives God such a primary role in the natural world that his activity seems to eclipse that of bodies. Much of the history of Cartesianism is the working out of these competing impulses. Part I then turns to an investigation of the concept of vis (force, power) in Descartes's work. Part II looks to the dialectic of occasionalism. It begins by exploring Malebranche's suite of arguments for occasionalism, some of which, as shall be seen in the book, have their origin in Descartes's own position. The book then turns to the case of Pierre-Sylvain Régis, who fights a rearguard action by at once revising and preserving some central Aristotelian notions within the general context of Cartesianism. Part III examines the Régis style of response to the Cartesian predicament as it appears in early modern empiricism. Part IV looks to Hume.
The Rejection of Aristotelianism
Authors: Ott Walter 
Published: September 2009

AbstractDescartes rejects scholastic powers because they have four related but to his mind equally repugnant features: they are not reducible to the mechanical properties of bodies; they are explanatorily impotent; they exhibit physical teleology; and, most importantly, they are characterized by physical intentionality. That is, a scholastic power is intrinsically directed toward its characteristic effect. In the context of ontological mechanism, this simply makes no sense. Descartes mocks the scholastics for having imbued bodies with “little souls” that direct their behavior.
The Laws of Nature
Authors: Ott Walter 
Published: September 2009

AbstractThis chapter discusses earlier conceptions (such as those of Aristotle and Aquinas) of the world as law‐governed, zeroing in on Descartes's contribution. In earlier views, we do not find the suggestion that laws are particular principles that might explain individual physical events. Nevertheless, Descartes retains a key feature of the legalistic metaphor: his laws depend on a lawgiver and are to that extent arbitrary. They swing entirely free from the natures of the objects whose behavior they prescribe.
‘A Dead Cadaverous Thing’
Authors: Ott Walter 
Published: September 2009

Abstract
In England, ontological mechanism comes under fire. Figures such as Ralph Cudworth and Henry More argue that this ontology is too impoverished to explain such phenomena as cohesion, gravity, the transference of motion, and witchcraft. It is by responding to these problems and to the challenges posed by the top‐down picture of the Cartesians that Locke and Boyle attempt to defend the bottom‐up view.
Boyle's Paradox
Authors: Ott Walter 
Published: September 2009

Abstract
Although Boyle's famous “lock and key” analogy seems to indicate that he takes powers to be nothing more than the intrinsic features of the bodies involved in their exercise, he also thinks that the distribution and conservation of motion is dependent on God's will. If this last point holds, however, then it is not clear how the key's power to open the lock could be reduced to the intrinsic features of the key and the lock. For if God were to vary the motion of these bodies, even keeping their intrinsic features the same, the key would gain and lose this power. This chapter suggests a solution to the paradox by sharpening up Boyle's seemingly reductive view of relations.
Locke on Powers: The Geometrical Model
Authors: Ott Walter 
Published: September 2009

AbstractLocke's ontology of relations and powers points to an alternative to the occasionalists' cognitive model of causality. So far, though, this is all it has done; it remains to be seen just how Locke proposes to account for the tie between cause and effect. Conceptual foundationalism offers the outlines of a story here: while there is no genuine, mind‐independent relation of cause and effect, there is still an objective ground on the basis of which a suitably disposed mind will (and should) think of this relation. What explains this ground is the geometrical model of causation. This chapter shows how the geometrical model fits with Locke's corpuscularianism and his claim that some geometrical propositions are synthetic and a priori. It also recasts Locke's distinction between primary and secondary qualities in such a way as to reconcile a number of seemingly conflicting texts.
Conclusion
Authors: Ott Walter 
Published: September 2009

AbstractAny attempt to resuscitate the powers of created beings, and hence the bottom‐up picture, must navigate between two obstacles. On one side lies occultism: given ontological mechanism, there seems no place for powers in nature, and nothing for them to do even if there were. On the other lurks voluntarism: if God is directly responsible for the distribution of motion, the bottom‐up view has been sacrificed, and the supervenience base of the powers of bodies must include more than their intrinsic properties. This chapter gathers up the threads of the previous ones to show precisely how Locke finds his own path between these two pitfalls.
The Two Humes
Authors: Ott Walter 
Published: September 2009

Abstract
Hume's Treatise has two distinct goals: first, to reveal the limitations of human knowledge by developing an empirical psychology, and second, to decide metaphysical questions. Many commentators take these to be in conflict, and so emphasize one or the other. This chapter suggests a way to unify them: by discovering the limits of human thought, Hume can declare certain metaphysical positions not just unknowable, or true for all we can tell, but positively nonsensical. The psychological project is thus in service of the metaphysical.
Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways
Authors: Sadreyev Ruslan I. , Feramisco Jamison D. , Tsao Hensin , Grishin Nick V. 
Published: September 2009

Abstract
Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene–disease associations with the many complex and overlapping phenotypes of human disease.
Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering. Placing the known gene–disease associations in the context of this space reveals new patterns that suggest previously unknown functional links between proteins, signaling pathways and disease phenotypes. For example, analysis of telangiectasias (spider vein diseases) reveals a previously unrecognized interplay between the TGF-β signaling pathway and pentose phosphate pathway. This interaction may mediate glucose-dependent regulation of TGF-β signaling, providing a clue to the known association between angiopathies and diabetes and implying new gene candidates for mutational analysis and drug targeting.
Contact: grishin@chop.swmed.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Developments in the field of allergy in 2008 through the eyes ofClinical & Experimental Allergy
Authors: Almqvist C. , Bradding P. B. , Chakir J. , Ebo D. , Grattan C. , Kariyawasam H. H. , Savilahti E. , Scadding G. K. , Vieths S. , Wardlaw A. J. , Woodfolk J. 
Published: September 2009

SummaryIn 2008, many thousands of articles were published on the subject of allergic disease with over 200 reviews, editorials and original papers inClinical & Experimental Allergyalone. These represent a considerable amount of data and even the most avid reader could only hope to assimilate a small fraction of this knowledge. There is therefore a pressing need for the key messages that emerge from a journal such asClinical & Experimental Allergyto be summarized by experts in the field in a form that highlights the significance of the developments and sets them in the context of important findings in the field published in other journals. This also has the advantage of making connections between new data in conditions such as asthma, where articles often appear in different sections of the journal. As can be seen from this review, the body of work is diverse both in terms of the disease of interest and the discipline that has been used to investigate it. However, taken as a whole, we hope that the reader will gain a flavour of where the field is mature, where there remain controversies and where the cutting edge is leading.
Intraseasonal climate and habitat‐specific variability controls the flowering phenology of high alpine plant species
Authors: Hülber Karl , Winkler Manuela , Grabherr Georg 
Published: September 2009

Summary 1.  High alpine plants endure a cold climate with short growing seasons entailing severe consequences of an improper timing of development. Hence, their flowering phenology is expected to be rigorously controlled by climatic factors. 2.  We studied ten alpine plant species from habitats with early and late melting snow cover for 2 years and compared the synchronizing effect of temperature sums (TS), time of snowmelt (SM) and photoperiod (PH) on their flowering phenology. Intraseasonal and habitat‐specific variation in the impact of these factors was analysed by comparing predictions of time‐to‐event models using linear mixed‐effects models. 3.  Temperature was the overwhelming trigger of flowering phenology for all species. Its synchronizing effect was strongest at or shortly after flowering indicating the particular importance of phenological control of pollination. To some extent, this pattern masks the common trend of decreasing phenological responses to climatic changes from the beginning to the end of the growing season for lowland species. No carry‐over effects were detected. 4.  As expected, the impact of photoperiod was weaker for snowbed species than for species inhabiting sites with early melting snow cover, while for temperature the reverse pattern was observed. 5.  Our findings provide strong evidence that alpine plants will respond quickly and directly to increasing temperature without considerable compensation due to photoperiodic control of phenology.
Differences in innate immune responses correlate with differences in murine susceptibility to Chlamydia muridarum pulmonary infection
Authors: Jiang Xiaozhou , Shen Caixia , Yu Hong , Karunakaran Karuna P. , Brunham Robert C. 
Published: September 2009

SummaryWe investigated the phenotypic basis for genetically determined differences in susceptibility and resistance to Chlamydia muridarum pulmonary infection using BALB/c and C57BL/6 mice. Following C. muridarum intranasal inoculation, the intensity of infection was very different between BALB/c and C57BL/6 beginning as early as 3 days post‐infection. Intrapulmonary cytokine patterns also differed at early time‐points (days 2 and 4) between these two strains of mice. The early recruitment of neutrophils to lung tissue was greater in BALB/c than in C57BL/6 mice and correlated with a higher number of inclusion forming units (IFU) of C. muridarum. At day 12 post‐infection, BALB/c mice continued to demonstrate a greater burden of infection, significantly higher lung cytokine levels for tumour necrosis factor‐α and interleukin‐17 (IL‐17) and a significantly lower level for interferon‐γ than did C57BL/6 mice. In vitro, bone‐marrow‐derived dendritic cells (BMDCs) from BALB/c mice underwent less functional maturation in response to C. muridarum infection than did BMDCs from C57BL/6 mice. The BMDCs of BALB/c mice expressed lower levels of activation markers (CD80, CD86, CD40 and major histocompatibility complex class II) and secreted less IL‐12 and more IL‐23 than BMDCs from C57BL/6 mice. Overall, the data demonstrate that the differences exhibited by BALB/c and C57BL/6 mice following C. muridarum pulmonary infection are associated with differences in early innate cytokine and cellular responses that are correlated with late differences in T helper type 17 versus type 1 adaptive immune responses.
Donor‐strain‐derived immature dendritic cell pre‐treatment induced hyporesponsiveness against allogeneic antigens
Authors: Kang Hee Gyung , Lee Jung Eun , Yang Seung Hee , Lee Se Han , Gao Wenda , Strom Terry B. , Oh Keunhee , Lee Dong‐Sup , Kim Yon Su 
Published: September 2009

SummaryThe maturation of antigen‐presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre‐treating recipients with bone‐marrow‐derived donor‐strain fixed immature DCs (FIDCs). Donor‐strain‐derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T‐cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T‐cell response. T cells that had previously been exposed to FIDCs maintained naïve phenotypes and were unable to extensively divide after injection into lethally irradiated donor‐strain mice. The pre‐treatment of recipients with donor‐strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T‐cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4+ CD25+ T cells. Consequently, FIDC‐induced T‐cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long‐term graft survival.
Protective role of osteopontin in endodontic infection
Authors: Rittling Susan R. , Zetterberg Craig , Yagiz Kader , Skinner Stephen , Suzuki Noriyuki , Fujimura Akira , Sasaki Hajime 
Published: September 2009

SummaryEndodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin‐binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well‐characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN‐deficient mice compared with wild‐type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin‐1α (IL‐1α) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria‐specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL‐12, IL‐10 and interferon‐γ. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN‐deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN‐deficient samples at this time‐point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections.
HHQ and PQS, two Pseudomonas aeruginosa quorum‐sensing molecules, down‐regulate the innate immune responses through the nuclear factor‐κB pathway
Authors: Kim Kiwan , Kim Young Uk , Koh Byung Hee , Hwang Soo Seok , Kim Seol‐Hee , Lépine Francois , Cho You‐Hee , Lee Gap Ryol 
Published: September 2009

SummaryTo explore whether bacterial secreted 4‐hydroxy‐2‐alkylquinolines (HAQs) can regulate host innate immune responses, we used the extracts of bacterial culture supernatants from a wild‐type (PA14) and two mutants of Pseudomonas aeruginosa that have defects in making HAQs. Surprisingly, the extract of supernatants from the P. aeruginosa pqsA mutant that does not make HAQs showed strong stimulating activity for the production of innate cytokines such as tumour necrosis factor‐α and interleukin‐6 in the J774A.1 mouse monocyte/macrophage cell line, whereas the extract from the wild‐type did not. The addition of 4‐hydroxy‐2‐heptylquinoline (HHQ) or 2‐heptyl‐3,4‐dihydroxyquinoline (PQS, Pseudomonas quinolone signal) to mammalian cell culture media abolished this stimulating activity of the extracts of supernatants from the pqsA mutant on the expression of innate cytokines in J774A.1 cells and in the primary bronchoalveolar lavage cells from C57BL/6 mice, suggesting that HHQ and PQS can suppress the host innate immune responses. The pqsA mutant showed reduced dissemination in the lung tissue compared with the wild‐type strain in a mouse in vivo intranasal infection model, suggesting that HHQ and PQS may play a role in the pathogenicity of P. aeruginosa. HHQ and PQS reduced the nuclear factor‐κB (NF‐κB) binding to its binding sites and the expression of NF‐κB target genes, and PQS delayed inhibitor of κB degradation, indicating that the effect of HHQ and PQS was mediated through the NF‐κB pathway. Our results suggest that HHQ and PQS produced by P. aeruginosa actively suppress host innate immune responses.
p21Cip1 up‐regulated during histone deacetylase inhibitor‐induced CD4+ T‐cell anergy selectively associates with mitogen‐activated protein kinases
Authors: Dagtas Ayse Selma , Gilbert Kathleen M. 
Published: September 2009

SummaryHistone deacetylase inhibitor n‐butyrate induced proliferative unresponsiveness in antigen‐stimulated murine CD4+ T cells. T cells anergized by n‐butyrate demonstrated reduced interleukin‐2 (IL‐2) secretion and decreased activating protein 1 (AP‐1) activity upon restimulation. Mechanistic studies determined that the cyclin‐dependent kinase (cdk) inhibitor p21Cip1 was up‐regulated in the anergic CD4+ T cells. p21Cip1 is known to inhibit the cell cycle through its interaction with cdk, proliferating cell nuclear antigen (PCNA) or c‐Jun N‐terminal kinase (JNK). p21Cip1 did not preferentially associate with PCNA or cdk in anergic T helper type 1 (Th1) cells. Instead, among the three interaction partners, p21Cip1 was found to interact with phospho‐JNK and phospho‐c‐jun selectively in the anergic CD4+ T cells. The activity of c‐jun and downstream transcription factor AP‐1 were suppressed in the anergic Th1 cells. In contrast, p21Cip1 and the two phospho‐proteins were never detected concurrently in the control CD4+ T cells. The n‐butyrate‐induced p21Cip1‐mediated inhibition of JNK and c‐jun represents a novel potential mechanism by which proliferative unresponsiveness was maintained in CD4+ T cells.
Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: A pilot study
Authors: Pecori Giraldi F. , Toja P. M. , Filippini B. , Michailidis J. , Scacchi M. , Stramba Badiale M. , Cavagnini F. 
Published: September 2009

SummarySymptoms and signs of male hypogonadism span all organ systems, including the cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac ventricular repolarization and, if prolonged, increases the risk of malignant arrhythmias. QT interval duration is similar in boys and girls during childhood, but shortens in males after puberty and experimental studies suggest that testosterone is a major contributor to shortening of QT interval in men. The aim of the present pilot study was to assess the duration of ventricular repolarization in adult males with primary or secondary hypogonadism. Standard ECG recordings were performed in 26 men (mean age 39.2 ± 2.17 years) with pituitary or testicular hypogonadism and repeated in 15 patients during testosterone replacement. Twenty‐six age‐matched control men were also analysed. Measured QT intervals were corrected for heart rate according to Bazzett’s formula (QTc = QT/√RR interval). The prevalence of prolonged QTc was considerably higher in hypogonadal patients (four of 26 men) than in control men (none,p < 0.05) and in the general, healthy population (<2.5%). QTc interval normalized on hormone replacement therapy in the four patients presenting prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did not differ among the two groups and no known QT‐prolonging factor was apparent in patients with abnormal QTc interval. In conclusion, a high number prolonged QT interval measurements was observed in hypogonadal men who may therefore be at increased risk for cardiac arrhythmias. This observation reveals an additional feature of male hypogonadism, which may benefit from testosterone replacement therapy.
Experiences of hospital care reported by bereaved relatives of patients after a stroke: a retrospective survey using the VOICES questionnaire
Authors: Young Amanda J. , Rogers Angie , Dent Louise , Addington‐Hall Julia M. 
Published: September 2009

AbstractTitle.  Experiences of hospital care reported by bereaved relatives of patients after astroke: a retrospective survey using the VOICES questionnaire. Aim.  This paper is a report of a study conducted to explore the determinants of satisfaction with health and social care services in the last 3 months and 3 days of life as reported by bereaved relatives of those who died from a stroke in an institutional setting.Background.  There is limited research about how best to meet the needs of those who die from stroke. A thorough understanding of the determinants of satisfaction with end of life care is crucial for effective service provision to increase awareness of the needs of dying patients.Methods.  During a six‐month period in 2003, a population‐based survey of bereaved relatives of patients after stroke was conducted using a stroke‐specific version of the Views of Informal Carers Evaluation of Services postal questionnaire (183 informants, response rate 37%). The sub‐sample included those informants who reported that the deceased person had died in an institutional setting (91%, n = 165). The analysis was divided into two phases: univariate (Pearson chi‐square test) and multivariate phase (logistic regression).Results.  Logistic regressions showed that discussing any worries about the treatment of the deceased person and feeling that the doctors and nurses knew enough about their condition were predictors of satisfaction with doctors and nurses in the last 3 months of life. Meeting the personal care needs of the deceased person, being involved in decisions and feeling that the deceased person died in the right place were predictors of satisfaction with care in the last 3 days of life.Conclusion.  End of life care needs to address the individual needs of patients who die from stroke and those close to them. This study shows that individualised end of life care increases satisfaction and, although the data reported in this paper reflect care in 2003, there is no more recent evidence that contradicts this important overall finding.