bluuebunny/crossref_metadata_2025 huggingface dataset:
A TORSIONAL TOPOLOGICAL INVARIANT
Authors: NIEH H. T.
Published: December 2007

Curvature and torsion are the two tensors characterizing a general Riemannian space–time. In Einstein's general theory of gravitation, with torsion postulated to vanish and the affine connection identified to the Christoffel symbol, only the curvature tensor plays the central role. For such a purely metric geometry, two well-known topological invariants, namely the Euler class and the Pontryagin class, are useful in characterizing the topological properties of the space–time. From a gauge theory point of view, and especially in the presence of spin, torsion naturally comes into play, and the underlying space–time is no longer purely metric. We describe a torsional topological invariant, discovered in 1982, that has now found increasing usefulness in recent developments.
VON KOCH AND THUE-MORSE REVISITED
Authors: ALLOUCHE J.-P. , SKORDEV G.
Published: December 2007

We revisit the relation between the von Koch curve and the Thue-Morse sequence given in a recent paper of Ma and Goldener by relating their study to papers written by Coquet and Dekking at the beginning of the 1980s. We also emphasize that more general links between fractal objects and automatic sequences can be found in the literature.
CENTRAL LIMIT THEOREM FOR THE LOG-REGRESSION WAVELET ESTIMATION OF THE MEMORY PARAMETER IN THE GAUSSIAN SEMI-PARAMETRIC CONTEXT
Authors: MOULINES E. , ROUEFF F. , TAQQU MURAD S.
Published: December 2007

We consider a Gaussian time series, stationary or not, with long memory exponent d ∈ ℝ. The generalized spectral density function of the time series is characterized by d and by a function f*(λ) which specifies the short-range dependence structure. Our setting is semi-parametric in that both d and f* are unknown, and only the smoothness of f* around λ = 0 matters. The parameter d is the one of interest. It is estimated by regression using the wavelet coefficients of the time series, which are dependent when d ≠ 0. We establish a Central Limit Theorem (CLT) for the resulting estimator [Formula: see text]. We show that the deviation [Formula: see text], adequately normalized, is asymptotically normal and specify the asymptotic variance.
WELL-POSED INITIAL-BOUNDARY VALUE PROBLEM FOR A CONSTRAINED EVOLUTION SYSTEM AND RADIATION-CONTROLLING CONSTRAINT-PRESERVING BOUNDARY CONDITIONS
Authors: ALEKSEENKO ALEXANDER M.
Published: December 2007

A well-posed initial-boundary value problem is formulated for the model problem of the vector wave equation subject to the divergence-free constraint. Existence, uniqueness and stability of the solution is proved by reduction to a system evolving the constraint quantity statically, i.e. the second time derivative of the constraint quantity is zero. A new set of radiation-controlling constraint-preserving boundary conditions is constructed for the free evolution problem. Comparison between the new conditions and the standard constraint-preserving boundary conditions is made using the Fourier–Laplace analysis and the power series decomposition in time. The new boundary conditions satisfy the Kreiss condition and are free from the ill-posed modes growing polynomially in time.
MASS CONCENTRATION WINDOW SIZE AND STRICHARTZ NORM DIVERGENCE RATE FOR THE L2-CRITICAL NONLINEAR SHRÖDINGER EQUATION
Authors: COLLIANDER JAMES , ROUDENKO SVETLANA
Published: December 2007

We observe a link between the window size of mass concentration and the rate of explosion of the Strichartz norm by revisiting Bourgain's mass concentration for the L2-critical nonlinear Schrödinger equations.
CONVERGENCE OF QUASI-LINEAR HYPERBOLIC EQUATIONS
Authors: SVANSTEDT NILS
Published: December 2007

Multiscale stochastic homogenization is studied for quasilinear monotone hyperbolic problems with a linear damping term. It is shown by classical G-convergence methods that the sequence of solutions to a class of multi-scale highly oscillatory (possibly random) hyperbolic problems converges in the appropriate Sobolev space to the solution to a homogenized quasilinear hyperbolic problem.
BOUNDS ON THE MINIMAL SUMSET SIZE FUNCTION IN GROUPS
Authors: ELIAHOU SHALOM , KERVAIRE MICHEL
Published: December 2007

In this paper, we give lower and upper bounds for the minimal size μG(r,s) of the sumset (or product set) of two finite subsets of given cardinalities r,s in a group G. Our upper bound holds for solvable groups, our lower bound for arbitrary groups. The results are expressed in terms of variants of the numerical function κG(r,s), a generalization of the Hopf–Stiefel function that, as shown in [6], exactly models μG(r,s) for G abelian.
FINITENESS RESULTS FOR REGULAR DEFINITE TERNARY QUADRATIC FORMS OVER ${\mathbb Q}(\sqrt{5})$
Authors: CHAN WAI KIU , EARNEST A. G. , ICAZA MARIA INES , KIM JI YOUNG
Published: December 2007

Let 𝔬 be the ring of integers in a number field. An integral quadratic form over 𝔬 is called regular if it represents all integers in 𝔬 that are represented by its genus. In [13,14] Watson proved that there are only finitely many inequivalent positive definite primitive integral regular ternary quadratic forms over ℤ. In this paper, we generalize Watson's result to totally positive regular ternary quadratic forms over [Formula: see text]. We also show that the same finiteness result holds for totally positive definite spinor regular ternary quadratic forms over [Formula: see text], and thus extends the corresponding finiteness results for spinor regular quadratic forms over ℤ obtained in [1,3].
ON THE SUMS OF COMPLEMENTARY DIVISORS
Authors: BECHEANU MIRCEA , LUCA FLORIAN , SHPARLINSKI IGOR E.
Published: December 2007

In this paper, we study various arithmetic properties of d + n/d, where d runs through all the τ(n) positive divisors of n. For example, denoting by ϖ(n) the number of prime values among these sums, we study how often ϖ(n) > 0 and also ϖ(n) = τ(n), and we also evaluate the average value of ϖ(n). We estimate some character sums with d + n/d and study the distribution of quadratic nonresidues and primitive roots among these sums on average over n ≤ x.
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.
DNA Transposons and the Evolution of Eukaryotic Genomes
Authors: Feschotte Cédric , Pritham Ellen J.
Published: December 2007

Transposable elements are mobile genetic units that exhibit broad diversity in their structure and transposition mechanisms. Transposable elements occupy a large fraction of many eukaryotic genomes and their movement and accumulation represent a major force shaping the genes and genomes of almost all organisms. This review focuses on DNA-mediated or class 2 transposons and emphasizes how this class of elements is distinguished from other types of mobile elements in terms of their structure, amplification dynamics, and genomic effect. We provide an up-to-date outlook on the diversity and taxonomic distribution of all major types of DNA transposons in eukaryotes, including Helitrons and Mavericks. We discuss some of the evolutionary forces that influence their maintenance and diversification in various genomic environments. Finally, we highlight how the distinctive biological features of DNA transposons have contributed to shape genome architecture and led to the emergence of genetic innovations in different eukaryotic lineages.
Specificity in Two-Component Signal Transduction Pathways
Authors: Laub Michael T. , Goulian Mark
Published: December 2007

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions. In the prototypical two-component system, a sensor histidine kinase catalyzes its autophosphorylation and then subseqeuntly transfers the phosphoryl group to a response regulator, which can then effect changes in cellular physiology, often by regulating gene expression. The utility of these signaling systems is underscored by their prevalence throughout the bacterial kingdom and by the fact that many bacteria contain dozens, or sometimes hundreds, of these signaling proteins. The presence of so many highly related signaling proteins in individual cells creates both an opportunity and a challenge. Do cells take advantage of the similarity between signaling proteins to integrate signals or diversify responses, and thereby enhance their ability to process information? Conversely, how do cells prevent unwanted cross-talk and maintain the insulation of distinct pathways? Here we address both questions by reviewing the cellular and molecular mechanisms that dictate the specificity of two-component signaling pathways.
Use of Y Chromosome and Mitochondrial DNA Population Structure in Tracing Human Migrations
Authors: Underhill Peter A. , Kivisild Toomas
Published: December 2007

Well-resolved molecular gene trees illustrate the concept of descent with modification and exhibit the opposing processes of drift and migration, both of which influence population structure. Phylogenies of the maternally inherited mtDNA genome and the paternally inherited portion of the nonrecombining Y chromosome retain sequential records of the accumulation of genetic diversity. Although knowledge regarding the diversity of the entire human genome will be needed to completely characterize human genetic evolution, these uniparentally inherited loci are unique indicators of gender in modulating the extant population structure. We compare and contrast these loci for patterns of continuity and discreteness and discuss how their phylogenetic diversity and progression provide means to disentangle ancient colonization events by pioneering migrants from subsequent overlying migrations. We introduce new results concerning Y chromosome founder haplogroups C, DE, and F that resolve their previous trifurcation and improve the harmony with the mtDNA recapitulation of the out-of-Africa migration.
Ellipsometric Measurements of the Plasma Oxidation of Nb and Ta and Their Interpretation
Authors: Knorr K. , Leslie J. D.
Published: December 2007

Ellipsometric results presented in this paper show that it is possible to grow a uniform Nb oxide film by plasma oxidation, and the index of refraction of this Nb oxide is 2.30. Similarly, in a previous paper we showed that plasma oxidation of Ta produced a uniform Ta oxide film with a refractive index of 2.21. These results are in contrast to the earlier work of Lee et al., who fitted their ellipsometric measurements on the plasma oxidation of Nb and Ta with two‐layer models. It is shown that the Nb and Ta oxides in the work of Lee et al. were not grown to a sufficient thickness to prove definitively that the oxides were composed of two layers, and that their data can be fitted equally well with one‐layer models.
A central role for hepatocyte growth factor in adipose tissue angiogenesis
Authors: Bell Lauren N. , Cai Liying , Johnstone Brian H. , Traktuev Dmitry O. , March Keith L. , Considine Robert V.
Published: December 2007

Hepatocyte growth factor (HGF) is a potent mitogenic and angiogenic factor produced in human adipose tissue. In this study, we use 3T3-F442A preadipocytes to study the contribution of HGF to angiogenesis in an in vivo fat pad development model. As observed for human adipocytes, HGF is synthesized and secreted by 3T3-F442A preadipocytes and mature adipocytes. HGF knockdown with small-interfering RNA reduced HGF mRNA expression 82.3 ± 4.2% and protein secretion 82.9 ± 1.4% from 3T3-F442A preadipocytes. Silencing of HGF resulted in a 70.5 ± 19.0% reduction in endothelial progenitor cell migration to 3T3-F442A-conditioned medium in vitro. 3T3-F442A preadipocytes injected under the skin of mice form a fat pad containing mature, lipid-filled adipocytes and a functional vasculature. At 72 h postinjection, expression of the endothelial cell genes TIE-1 and platelet endothelial cell adhesion molecule (PECAM)-1 was decreased 94.4 ± 2.2 and 91.5 ± 2.5%, respectively, in 3T3-F442A fat pads with HGF silencing. Knockdown of HGF had no effect on differentiation of 3T3-F442A preadipocytes to mature adipocytes in vitro or in vivo. In developing fat pads under the skin of HGF overexpressing transgenic mice, TIE-1 and PECAM-1 mRNA was increased 16.5- and 21.4-fold, respectively, at 72 h postinjection. The increase in gene expression correlated with immunohistochemical evidence of endothelial cell migration in the developing fat pad. These data suggest that HGF has a central role in regulating angiogenesis in adipose tissue.
Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-κB activation via NADPH oxidase
Authors: Wei Yongzhong , Sowers James R. , Clark Suzanne E. , Li Wenhan , Ferrario Carlos M. , Stump Craig S.
Published: December 2007

Reduced insulin sensitivity is a key factor in the pathogenesis of type 2 diabetes and hypertension. Skeletal muscle insulin resistance is particularly important for its major role in insulin-mediated glucose disposal. Angiotensin II (ANG II) is integral in regulating blood pressure and plays a role in the pathogenesis of hypertension. In addition, we have documented that ANG II-induced skeletal muscle insulin resistance is associated with generation of reactive oxygen species (ROS). However, the linkage between ROS and insulin resistance in skeletal muscle remains unclear. To explore potential mechanisms, we employed the transgenic TG(mRen2)27 (Ren-2) hypertensive rat, which harbors the mouse renin transgene and exhibits elevated tissue ANG II levels, and skeletal muscle cell culture. Compared with Sprague-Dawley normtensive control rats, Ren-2 skeletal muscle exhibited significantly increased oxidative stress, NF-κB activation, and TNF-α expression, which were attenuated by in vivo treatment with an angiotensin type 1 receptor blocker (valsartan) or SOD/catalase mimetic (tempol). Moreover, ANG II treatment of L6 myotubes induced NF-κB activation and TNF-α production and decreased insulin-stimulated Akt activation and GLUT-4 glucose transporter translocation to plasma membranes. These effects were markedly diminished by treatment of myotubes with valsartan, the antioxidant N-acetylcysteine, NADPH oxidase-inhibiting peptide (gp91 ds-tat), or NF-κB inhibitor (MG-132). Similarly, NF-κB p65 small interfering RNA reduced NF-κB p65 subunit expression and nuclear translocation and TNF-α production but improved insulin-stimulated phosphorylation (Ser473) of Akt and translocation of GLUT-4. These findings suggest that NF-κB plays an important role in ANG II/ROS-induced skeletal muscle insulin resistance.
PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle
Authors: Leick Lotte , Wojtaszewski Jørgen F. P. , Johansen Sune T. , Kiilerich Kristian , Comes Gemma , Hellsten Ylva , Hidalgo Juan , Pilegaard Henriette
Published: December 2007

The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-γ coactivator (PGC) 1α is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1α knockout (KO) and littermate wild-type (WT) mice performed a single treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1α KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained ∼37 h after the last training session. Resting muscles of the PGC-1α KO mice had lower (∼20%) cytochrome c (cyt c), cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK) α1, AMPKα2, and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-β and the level of HKII mRNA similarly in WG of KO and WT. In contrast, cyt c mRNA in soleus was upregulated in WT muscles only. Exercise training increased cyt c, COXI, ALAS1, and HKII mRNA and protein levels equally in WT and KO animals, but cyt c, COXI, and ALAS1 expression remained ∼20% lower in KO animals. In conclusion, lack of PGC-1α reduced resting expression of cyt c, COXI, and ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1α is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1α can exert these adaptations.
Macaque V1 Activity During Natural Vision: Effects of Natural Scenes and Saccades
Authors: MacEvoy Sean P. , Hanks Timothy D. , Paradiso Michael A.
Published: December 2007

In the present study, we examined the way that scene complexity and saccades combine to sculpt the temporal response patterns of V1 neurons. To bridge the gap between conventional and free viewing experiments, we compared responses of neurons across four paradigms ranging from less to more natural. An optimal bar stimulus was either flashed into a receptive field (RF) or brought into it via saccade and was embedded in either a natural scene or a uniform gray background. Responses to a flashed bar tended to be higher with a uniform rather than natural background. The most novel result reported here is that responses evoked by stimuli brought into the RF via saccades were enhanced compared with the same stimuli flashed during steady fixation. No single factor appears to account entirely for this surprising effect, but there were small contributions from fixational saccades and residual activity carried over from the previous fixation. We also found a negative correlation with cells' response “history” in that a larger response on one fixation was associated with a lower response on the subsequent fixation. The effects of the natural background and saccades exhibited a significant nonlinear interaction with the suppressive effects of the natural background less for stimuli entering RFs with saccades. Together, these results suggest that even responses to standard optimal stimuli are difficult to predict under conditions similar to natural vision, and further demonstrate the importance of naturalistic experimental paradigms to the study of visual processing in V1.
Performance Monitoring Local Field Potentials in the Medial Frontal Cortex of Primates: Anterior Cingulate Cortex
Authors: Emeric Erik E. , Brown Joshua W. , Leslie Melanie , Pouget Pierre , Stuphorn Veit , Schall Jeffrey D.
Published: December 2007

We describe intracranial local field potentials (LFP) recorded in the anterior cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding task. The most prominent feature at ∼70% of sites was greater negative polarity after errors than after rewarded correct trials. This negative polarity was also evoked in unrewarded correct trials. The LFP evoked by the visual target was much less polarized, and the weak presaccadic modulation was insufficient to control the initiation of saccades. When saccades were cancelled, LFP modulation decreased slightly with the magnitude of response conflict that corresponds to the coactivation of gaze-shifting and -holding neurons estimated from the probability of canceling. However, response time adjustments on subsequent trials were not correlated with LFP polarity on individual trials. The results provide clear evidence that error- and feedback-related, but not conflict-related, signals are carried by the LFP in the macaque ACC. Finding performance monitoring field potentials in the ACC of macaque monkeys establishes a bridge between event-related potential and functional brain-imaging studies in humans and neurophysiology studies in non-human primates.
Effects of short-term growth hormone treatment on liver and muscle transcriptomes in rainbow trout (Oncorhynchus mykiss)
Authors: Gahr Scott A. , Vallejo Roger L. , Weber Gregory M. , Shepherd Brian S. , Silverstein Jeffrey T. , Rexroad Caird E.
Published: December 2007

Although studies have established that exogenous growth hormone (GH) treatment stimulates growth in fish, its effects on target tissue gene expression are not well characterized. We assessed the effects of Posilac (Monsanto, St. Louis, MO), a recombinant bovine GH, on tissue transcript levels in rainbow trout selected from two high-growth rate and two low-growth rate families. Transcript abundance was measured in liver and muscle with the Genome Research in Atlantic Salmon Project (GRASP) 16K cDNA microarray. A selection of the genes identified as altered by the microarray and transcripts for insulin-like growth factors, growth hormone receptors (GHRs), and myostatins were measured by real-time PCR in the liver, muscle, brain, kidney, intestine, stomach, gill, and heart. In general, transcripts identified as differentially regulated in the muscle on the microarray showed similar directional changes of expression in the other nonhepatic tissues. A total of 114 and 66 transcripts were identified by microarray as differentially expressed with GH treatment across growth rate for muscle and liver, respectively. The largest proportion of these transcripts represented novel transcripts, followed by immune and metabolism-related genes. We have identified a number of genes related to lipid metabolism, supporting a modulation in lipid metabolism following GH treatment. Most notable among the growth-axis genes measured by real-time PCR were increases in GHR1 and -2 transcripts in liver and muscle. Our results indicate that short-term GH treatment activates the immune system, shifts the metabolic sectors, and modulates growth-regulating genes.
Hsp27 Modulates p53 Signaling and Suppresses Cellular Senescence
Authors: O'Callaghan-Sunol Cornelia , Gabai Vladimir L. , Sherman Michael Y.
Published: December 2007

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

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

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

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]
Cardiovascular Risk Factors and Venous Thromboembolism
Authors: Ageno Walter , Becattini Cecilia , Brighton Timothy , Selby Rita , Kamphuisen Pieter W.
Published: December 2007

Background—

The concept that venous thromboembolism (VTE) and atherosclerosis are 2 completely distinct entities has recently been challenged because patients with VTE have more asymptomatic atherosclerosis and more cardiovascular events than control subjects. We performed a meta-analysis to assess the association between cardiovascular risk factors and VTE.

Methods and Results—

Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and control subjects. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics, study quality, and outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of χ
2
and I
2
statistics. Twenty-one case-control and cohort studies with a total of 63 552 patients met the inclusion criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to 1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean high-density lipoprotein cholesterol levels were significantly lower in VTE patients, whereas no difference was observed for total and low-density lipoprotein cholesterol levels. Significant heterogeneity among studies was present in all subgroups except for the diabetes mellitus subgroup. Higher-quality studies were more homogeneous, and significant associations remained unchanged.

Conclusions—

Cardiovascular risk factors are associated with VTE. This association is clinically relevant with respect to individual screening, risk factor modification, and primary and secondary prevention of VTE. Prospective studies should further investigate the underlying mechanisms of this relationship.
Urotensin II and Cardiomyopathy in End-Stage Renal Disease
Authors: Zoccali Carmine , Mallamaci Francesca , Benedetto Frank Antonio , Tripepi Giovanni , Pizzini Patrizia , Cutrupi Sebastiano , Malatino Lorenzo
Published: December 2007

Circulating urotensin (UTN) is increased in patients with heart failure and in patients with renal diseases, and UTN antagonism is currently considered as a potential treatment for these conditions. Contrary to this contention, studies in end-stage renal disease suggest that, perhaps because of interference with sympathetic and NO systems, UTN may be cardioprotective. Therefore, we investigated the relationship between circulating UTN and echocardiographic parameters of left ventricular function (midwall fractional shortening), left atrial volume, and myocardial geometry (mean wall thickness and relative wall thickness) in 191 patients with end-stage renal disease. UTN was associated directly (
r
=0.39;
P
<0.001) with left ventricular systolic function and inversely with left atrial volume (
r
=−0.40;
P
<0.001) and the muscular component of the left ventricular (UTN versus mean wall thickness:
r
=−0.30,
P
<0.001; UTN versus relative wall thickness:
r
=−0.32,
P
<0.001). Adjustment for a series of 11 risk factors produced a relatively small change in the strength of these relationships. However, further adjustment for plasma norepinephrine or, particularly so, for the endogenous inhibitor of NO synthase asymmetrical dimethyl arginine produced a 33% to 50% decrease in the strength of such associations. Of note, there was a strong UTN-asymmetrical dimethyl arginine interaction in determining midwall fractional shortening (
P
=0.001) and mean wall thickness (
P
=0.006). These data support the hypothesis that high UTN is cardioprotective in end-stage renal disease and that interference by UTN with sympathetic activity and NO synthesis represents an intermediate mechanism mediating the favorable echocardiographic profile of patients with high UTN. Additional mechanistic insights may be needed before launching long-term clinical trials with UTN antagonists in patients with end-stage renal disease.
La Beata Laura Vicuña: The Nun's Version, Corrective of García Márquez's
Authors: Cussen John
Published: December 2007

This 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

This 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

Three 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

Whereas 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

South 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

Tenth-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

In 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

The 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

John 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

Leiden 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.