bluuebunny/crossref_metadata_2025 huggingface dataset:
Putting on the RITz
Authors: Kaech Stefanie , Banker Gary , Stork Phillip
Published: December 2007

Neurons develop two types of processes, axons and dendrites, whose growth must be independently controlled. Recent research has identified the small guanosine triphosphatase Rit as a differential regulator of neurite growth. Activation of Rit enhances axonal growth, whereas inhibition of Rit promotes dendritic growth. These results imply that the reciprocal regulation of a single molecule in the same cell can achieve simultaneous regulation of axonal and dendritic growth.
Place Spindle Here
Authors: Gough Nancy R.
Published: December 2007

Nonpolarized cultured cells that adhere to the substrate on which they are growing orient their spindles parallel to the substratum, thereby allowing both daughter cells to maintain contact with the substrate. Interactions between the astral microtubules and various microtubule-organizing proteins, including the minus end-directed motor complex and the dynein-dynactin complex, are involved in connecting the spindle to the actin cytoskeleton and the cell cortex. Now Toyoshima
et al
. find that, in HeLa cells, integrin-mediated stimulation of phosphoinositide 3-kinase (PI3K) leading to the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P
3
] at the midsection of the cell cortex in metaphase cells was required for proper spindle orientation. PI(3,4,5)P
3
concentration was monitored with a green fluorescent protein fused to the pleckstrin homology domain of Akt (Akt-PH-GFP), and the midsection cortical localization, as well as proper spindle orientation, was lost if PI3K activity was inhibited pharmacologically or if β1 integrin was knocked down with RNAi. In contrast, polarized MDCK cells did not require PI3K signaling to achieve proper spindle orientation and instead appeared to rely on an interaction of the spindle with the adherens junction (see Gachet and Tournier). The dynein-dynactin complex associates with the astral microtubules, and inhibition of PI3K prevented the localization of the dynein-dynactin complex to the midsection of the cell. Furthermore, in cells in which PI3K was inhibited, the chromosomes rotated in the
z
axis, and this rotation was eliminated in cells in which dynein activity was inhibited using RNAi techniques. An open question is how integrin signaling, which occurs at the bottom of the cell at the sites of cell attachment to the substrate, leads to the accumulation of PI(3,4,5)P
3
at the midsection of the cell cortex.

F. Toyoshima, S. Matsumura, H. Morimoto, M. Mitsushima, E. Nishida, PtdIns(3,4,5)P3 regulates spindle orientation in adherent cells.
Dev. Cell
13
, 796-811 (2007).
[PubMed]

Y. Gachet, S. Tournier, Lost your orientation? Find your way with PtdIns(3,4,5)P3!
Dev. Cell
13
, 753-754 (2007).
[PubMed]
c-Myc to Melanoma Cells: Drop Dead?
Authors: Foley John F.
Published: December 2007

Because the proteasome regulates the cell cycle and apoptosis, proteasome inhibitor-mediated tumor cell death is not that surprising. What is puzzling, however, given the vital role of the proteasome in protein turnover, is the paucity of side effects on normal cells. What makes protease inhibitors so tumor cell-selective? One such compound, bortezomib, increases the abundance, in cancer cells but not in normal cells, of the mRNA and protein of the proapoptotic factor, NOXA. Nikiforov
et al
. investigated the mechanism by which bortezomib causes cell death in melanoma cell lines. Western blotting analysis showed that the bortezomib-dependent increase in NOXA abundance in melanoma cells was blocked by the transcriptional inhibitor actinomysin D. Bortezomib still increased the abundance of NOXA in cell lines that were treated with short interfering RNAs specific for those transcription factors known to target
NOXA
: p53, hypoxia-inducible factor-1α (HIF-1α), and E2F-1. Computational analysis of the sequences surrounding the
NOXA
promoter revealed the presence of four putative binding sites for the oncoprotein c-Myc. Chromatin immunoprecipitation assays confirmed the binding of c-Myc to the
NOXA
promoter, whose abundance was increased, compared with control cells, after treatment with bortezomib. Knockdown of c-Myc in melanoma cells blocked the bortezomib-dependent increase in NOXA abundance, whereas overexpression of c-Myc in normal melanocytes increased the abundance of
NOXA
mRNA, which was further enhanced by bortezomib treatment. Overexpression of c-Myc in melanoma cells sensitized them to the effects of bortezomib, whereas knockdown of NOXA inhibited bortezomib-induced cell death. Together, these data suggest the unusual involvement of c-Myc in promoting apoptosis and provide a possible mechanism for the tumor cell-specific effect of proteasome inhibitors.

M. A. Nikiforov, M. Riblett, W.-H. Tang, V. Gratchouck, D. Zhuang, Y. Fernandez, M. Verhaegen, S. Varambally, A. M. Chinnaiyan, A. J. Jakubowiak, M. S. Soengas, Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome inhibition.
Proc. Natl. Acad. Sci. U.S.A.
104
, 19488-19493 (2007).
[Abstract]
[Full Text]
Drugs, Psychosis, and Schizophrenia
Authors: Stern Peter
Published: December 2007

It is well established that the psychosis-inducing effects of the dissociative anesthetics phencyclidine (PCP) and ketamine, when used at subanesthetic doses such as in drug abuse, are produced by blockade of neurotransmission at
N
-methyl-D-aspartate (NMDA)-type glutamate receptors. However, their mechanisms of action at the brain circuitry level are poorly understood. Behrens
et al
. found that exposure of mice to subanesthetic doses of ketamine triggers an early and profound increase in neuronal superoxide production that is specifically due to induction of the inflammatory enzyme complex, NADPH oxidase-2 (Nox2). This in turn leads to the loss of phenotype of a specific subset of GABAergic interneurons, the parvalbumin-positive (PV) fast-spiking interneurons. Prevention of superoxide effects in the brain using a brain-permeable superoxide dismutase mimetic, as well as apocynin, a Nox2 inhibitor, strongly attenuated the ketamine-induced loss of parvalbumin and GAD67 immunoreactivity.

M. M. Behrens, S. S. Ali, D. N. Dao, J. Lucero, G. Shekhtman, K. L. Quick, L. L. Dugan, Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase.
Science
318
, 1645-1647 (2007).
[Abstract]
[Full Text]
Avoiding Resistance
Authors: Zahn Laura M.
Published: December 2007

Among the most commonly used classes of pesticides are toxins produced by the bacteria
Bacillus thuringiensis
, known as Bt toxins. The primary threat to the efficacy of Bt toxins is the evolution of resistance by pests. In major pests, resistance to Bt toxins in the Cry1A family is linked to alterations in cadherin proteins that act as primary toxin receptors in the midgut of susceptible insects. Now Soberón
et al
. (see the Perspective by Moar) show that engineered Bt toxins can overcome insect resistance. Furthermore, in investigating the effectiveness of these engineered proteins, the authors provided evidence for the means by which these toxins cause mortality in insects.

M. Soberón, L. Pardo-López, I. López, I. Gómez, B. E. Tabashnik, A. Bravo, Engineering modified Bt toxins to counter insect resistance.
Science
318
, 1640-1642 (2007).
[Abstract]
[Full Text]

W. J. Moar, K. J. Anilkumar, The power of the pyramid.
Science
318
, 1561-1562 (2007).
[Summary]
[Full Text]
IP
6
Got Rhythm?
Authors: Foley John F.
Published: December 2007

Motile cilia are plasma membrane projections that contain a central core of microtubules whose movement relative to each other contributes to ciliary beating. The left-right body patterning of developing embryos is thought to result from cilia-dependent differential distribution of morphogens. Knockout of inositol 1,3,4,5,6-pentakisphosphate (IP
5
) 2-kinase (Ipk1), the enzyme that synthesizes IP
6
, in zebrafish embryos results in defective left-right positioning of organs, although the mechanism involved is unknown. Sarmah
et al
. extended this work and knocked down expression of
ipk1
in zebrafish by injecting embryos with an antisense morpholino oligonucleotide (MO) targeted to
ipk1
mRNA (
ipk1
MO1
embryos). The Kupffer’s vesicle (KV) is the organ that initiates left-right organ placement in the zebrafish. The authors found that whereas KV cilia from wild-type embryos beat with a regular frequency in a counterclockwise direction, those from
ipk1
MO1
embryos vibrated without a defined direction of motion. Furthermore, immunocytochemical analyses revealed that cilia in
ipk1
MO1
embryos were shorter than those in wild-type embryos. Although the ectopic expression in
ipk1
MO1
embryos of Ipk1 resulted in the rescue of ciliary length and motion, that of a catalytically inactive mutant of Ipk1 did not. Fluorescence microscopy showed that Ipk1 was localized to centrosomes in the basal bodies of cilia in wild-type embryos. Transmission electron microscopy demonstrated that the organization of microtubules in the cilia from
ipk1
MO1
embryos was similar to that in wild-type embryos. However, the anterograde microtubule-dependent movement of melanosomes (pigmented vesicles), which is mediated by kinesin proteins, was much slower in
ipk1
MO1
cilia than in wild-type cilia. Together these data implicate Ipk1, and potentially its product IP
6
, in the maintenance of cilia length and the regulation of ciliary motion.

B. Sarmah, V. P. Winfrey, G. E. Olson, B. Appel, S. R. Wente, A role for the inositol kinase Ipk1 in ciliary beating and length maintenance.
Proc. Natl. Acad. Sci. U.S.A.
104
, 19843-19848 (2007).
[Abstract]
[Full Text]
PIKing Oncogenic Mutations
Authors: Vinson Valda
Published: December 2007

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that can initiate a variety of signaling events. Many human cancers involve mutations that activate PI3Kα, a heterodimer composed of a catalytic subunit, p110α, and a regulatory subunit, p85α, both of which contain multiple domains. Huang
et al.
describe the crystal structure of a complex between the full-length human p110α catalytic subunit and the binding and activation domains of the p85α regulatory subunit. The structure provides insight into how oncogenic mutations affect enzyme activity and could assist in the future design of isoform- or mutation-specific inhibitors.

C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, L. M. Amzel, The structure of a human p110α/p85α complex elucidates the effects of oncogenic PI3Kα mutations.
Science
318
, 1744-1748 (2007).
[Abstract]
[Full Text]
The Pros and Cons of Acetylation
Authors: Ray L. Bryan
Published: December 2007

Hirayama
et al
. provide new understanding of the signaling feedback loops that control the mammalian circadian clock. CLOCK and BMAL1 are clock proteins that form a complex and promote clock-controlled transcription of target genes. CLOCK is a histone acetyltransferase that acts to regulate gene expression by initiating remodeling of chromatin. The new work showed that CLOCK acetylated its binding partner BMAL1 when transfected, tagged proteins were expressed in cultured cells or when purified proteins were mixed in vitro. Reconstitution of mouse embryo fibroblasts lacking BMAL1 with a BMAL mutant that lacked the lysine residue acetylated by CLOCK failed to restore circadian gene regulation. Acetylation of BMAL1 appeared to increase association of the CLOCK-BMAL1 complex with cryptochrome 1 (Cry1), which acts as a repressor of CLOCK-BMAL1-induced transcription. Cry1-mediated repression was lacking in cells expressing the acetylation-deficient mutant of BMAL1, and interaction of Cry1 with the CLOCK-BMAL1 complex was lost in a two-hybrid assay with the mutant BMAL1. Acetylation of BMAL1 in vivo also occurs at a time in the circadian cycle when transcription of clock-controlled genes is diminished. Thus, the authors conclude that acetylation of BMAL1 by its binding partner CLOCK contributes to a negative feedback loop that decreases clock-regulated transcription. The positive and negative feedback loops thus appear to be tightly associated because CLOCK’s effect on BMAL contrasts with its role in acetylation of histones, which stimulates transcription of clock-dependent genes.

J. Hirayama, S. Sahar, B. Grimaldi, T. Tamaru, K. Takamatsu, Y. Nakahata, P. Sassone-Corsi, CLOCK-mediated acetylation of BMAL1 controls circadian function.
Nature
,
450
, 1086-1090 (2007).
[PubMed]
Circadian Rhythm Methods
Authors: Ray L. Bryan , Hines Pamela J.
Published: December 2007

Circadian rhythms in plants and animals appear to be coupled to periodic changes in activity of metabolic pathways (see the Perspective by Imaizumi
et al.
). Yin
et al.
describe a molecular mechanism that may contribute to the coordination of these biochemical processes. Rev-erbα controls transcription of the gene encoding the circadian clock component Bmal1. Rev-erbα binds to and is regulated by heme, which stabilizes Rev-erbα in a repressor complex, which in turn can block production of gluconeogenic enzymes. Thus, Rev-erbα acts as a heme sensor to coordinate the cellular clock, glucose homeostasis, and energy metabolism in human liver cells. Studying
Arabidopsis
, Dodd
et al.
now show that a cytoplasmic signaling molecule, cyclic adenosine diphosphate ribose (cADPR), is also a component of the clock mechanism. Perturbations to the feedback loop including cADPR result in instabilities in the clock and disruptions in the daily oscillations of cytoplasmic Ca
2+
release.

L. Yin, N. Wu, J. C. Curtin, M. Qatanani, N. R. Szwergold, R. A. Reid, G. M. Waitt, D. J. Parks, K. H. Pearce, G. B. Wisely, M. A. Lazar, Rev-erbα, a heme sensor that coordinates metabolic and circadian pathways.
Science
318
, 1786-1789 (2007).
[Abstract]
[Full Text]

A. N. Dodd, M. J. Gardner, C. T. Hotta, K. E. Hubbard, N. Dalchau, J. Love, J.-M. Assie, F. C. Robertson, M. K. Jakobsen, J. Gonçalves, D. Sanders, A. A. R. Webb, The
Arabidopsis
circadian clock incorporates a cADPR-based feedback loop.
Science
318
, 1789-1792 (2007).
[Abstract]
[Full Text]

T. Imaizumi, S. A. Kay, J. I. Schroeder, Daily watch on metabolism.
Science
318
, 1730-1731 (2007).
[Summary]
[Full Text]
Loss of Bactericidal Activity Promotes Infection
Authors: Gough Nancy R.
Published: December 2007

Chronic lung disease, including cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease (COPD), is characterized by high concentrations of interleukin-8 (IL-8) in cells around the airway and accumulation of neutrophils, yet the lungs of these patients are frequently colonized by bacteria, such as
Pseudomonas aeruginosa
. Hartl
et al
. show that IL-8 acts through the CXCR1 receptor, not the CXCR2 receptor, to promote the bactericidal activity of neutrophils. By comparing neutrophils from the peripheral blood and airway (bronchial alveolar lavage and sputum) of healthy individuals with those from patients with cystic fibrosis, bronchiectasis, or COPD, Hartl
et al
. found that the airway neutrophils from the diseased lungs had decreased CXCR1 at the surface and exhibited impaired bactericidal activity. The protease elastase is increased in abundance in airway fluids from patients with cystic fibrosis. Further statistical analysis of various factors associated with cystic fibrosis, including infection with
P. aeruginosa
, suggested that the concentration of free elastase correlated with the loss of CXCR1 on the airway neutrophils. Addition of airway fluids from individuals with cystic fibrosis to peripheral neutrophils caused loss of CXCR1 and impaired bacterial killing, and these effects were prevented if the elastase activity was inhibited pharmacologically in the airway fluid prior to addition to the isolated neutrophils. Cleavage of CXCR1 by elastase produced two soluble CXCR1 fragments that were also detected in the airway fluids from patients with cystic fibrosis, bronchiectasis, or COPD. Application of purified soluble CXCR1 fragments stimulated bronchial epithelial cells to produce IL-8 through a mechanism requiring the Toll-like receptor TLR2. Cystic fibrosis patients who inhaled α1 antitrypsin to inhibit elastase activity for 4 weeks showed increased CXCR1 at the surface of airway neutrophils, decreased abundance of soluble CXCR1 fragments in the airway fluid, and decreased
P. aeruginosa
in the sputum. In commentary, Sabroe and Whyte describe how failure of mucosal immunity contributes to disease pathogenesis, especially in cystic fibrosis.

D. Hartl, P. Latzin, P. Hordijk, V. Marcos, C. Rudolph, M. Woischnik, S. Krauss-Etschmann, B. Koller, D. Reinhardt, A. A. Roscher, D. Roos, M. Griese, Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease.
Nat. Med.
13
, 1423-1430 (2007).
[PubMed]

I. Sabroe, M. K. B. Whyte, Incapacitating the immune system in cystic fibrosis.
Nat. Med.
13
, 1417-1418 (2007).
[PubMed]
FORCED SYNCHRONIZATION OF EUKARYOTIC CELLS
Authors: BATTOGTOKH DORJSUREN
Published: December 2007

A comprehensive mathematical model of the budding yeast cell cycle, accounting for several dozen published experiments, has thirty five variables and one hundred and forty parameters.5 Detailed models describing cell cycle regulation in other organisms have also a large number of variables and parameters. Complexity rises further upon integrating the cell cycle network to other pathways in the cell. For some practical and theoretical issues, abundant complexity in realistic models can be tackled by studying first a functional subset of a model to understand the mechanism of a concerned process, and then by revealing the conditions of its occurrence in a detailed model. Here we review this approach applied to the problem of cell synchronization. Using analytic results obtained from a minimal model, we simulate cell synchronization in comprehensive mathematical models for budding and fission yeast cell cycles. Our results demonstrate that an experimental method based on periodic forcing of the synthesis of cell cycle regulators can be a powerful tool for cell synchronization.
CASCADES IN SMALL-WORLD MODULAR NETWORKS WITH CML'S METHOD
Authors: CUI DI , GAO ZIYOU , ZHAO XIAOMEI
Published: December 2007

This paper presents a possible and reasonable explanation of cascading failure in small-world modular networks. We aim to introduce the CML's method to interpret the mechanism of cascading failure in small-world modular networks with different rewiring probability of inner-module and inter-module. The cascade propagation of such networks with the different initial external perturbation is simulated. Additionally, it is found that the perturbation threshold has close relationships with the modularity, the mean node degree and the rewiring probability. Based on the numerical simulation, we can see that the larger mean node degree can delay the cascading failure process. Furthermore, the small value of rewiring probability and larger modularity can efficiently delay the breakdown caused by the cascading failure. It is particularly important for controlling the cascading failure process in small-world modular networks.
NOISE-IMPROVED SIGNAL CORRELATION IN AN ARRAY OF AUTOREGRESSIVE MODELS OF ORDER ONE
Authors: WANG YOUGUO , WU LENAN
Published: December 2007

This paper discusses noise-improved signal correlation through an array of autoregressive models of order one [AR (1)]. In a single model, when the input is a square wave or a cosine with a higher frequency, stochastic resonance (SR) exists. When the input is a cosine with a lower frequency, SR and suprathreshold stochastic resonance (SSR) both exist. SSR can also exist for a cosine with a higher frequency or a square wave through an array of AR (1) models. The efficacy of SR and SSR increases as the number of AR (1) models is raised or as the threshold is lowered in the array. There is a range of values of noise standard deviation where the correlation coefficient between the input and output signals is greater than that of the input signal and the noisy signal.
VIBRATION-INDUCED CONDUCTIVITY FLUCTUATION MEASUREMENT FOR SOIL BULK DENSITY ANALYSIS
Authors: KISHNÉ A. SZ. , MORGAN C. L. S. , CHANG H. -C. , KISH L. B.
Published: December 2007

Soil bulk density is a physical property of soils that affects water storage, water and nutrient movement, and plant root activity in the soil profile. The ability to quantify soil bulk density using vibration-induced conductivity fluctuation was investigated with possible field applications in the future. The AC electrical conductance of soil was measured using a pair of blade-like electrodes while exposing to periodic vibration. The blades were positioned longitudinally and transversally to the direction of the induced vibration to enable the calculation of a normalized index. This normalized index was expected to provide data independent from the vibration strength, and to reduce the effect of soil salinity and water content. Simulations on a simplified resistor lattice indicate that the ratio of transversal and longitudinal fluctuation decreases as soil bulk density increases. The experiment was conducted on natural and salinized fine sand at two moisture conditions and four compaction levels. The blade-shaped electrodes improved electrode-soil contact compared to cylindrical electrodes, and thereby, reduced measurement noise. Dry sand measurements showed an inverse correlation between the normalized conductivity fluctuation and soil bulk density for both longitudinal and transversal fluctuation. The wet natural and salinized soils performed very similarly as hypothesized, but their normalized VICOF response was not associated with bulk density changes. This lack of sensitivity might be attributed to the heavy electrodes and/or the specific vibration method used. The effects of electrode material, vibration method and soil properties on the experiment need further study.
DETECTION AND ESTIMATION OF MULTIPLE WEAK SIGNALS IN NON-GAUSSIAN NOISE
Authors: NELSON D. J.
Published: December 2007

We address the problem of efficient detection and estimation of multiple weak signals in severe noise. To address this problem, we propose a concentrated peak representation (CPR) in which the spectral energy is concentrated in spectral peaks, and only the magnitudes and locations of the peaks are retained. We base our process on the cross spectral representation we have previously applied to other problems. The advantage of this representation is that it preserves the energy in signal components while significantly reducing the data volume. We demonstrate the method on a composite signal consisting of one billion samples, reducing the data volume by a factor of 1000 or more, and we demonstrate the detection of weak signals in the reduced representation.
TWO-STEP NILPOTENT LIE ALGEBRAS WITH AD-INVARIANT METRICS AND A SPECIAL KIND OF SKEW-SYMMETRIC MAPS
Authors: OVANDO GABRIELA
Published: December 2007

We prove that a 2-step nilpotent Lie algebra admitting an ad-invariant metric can be constructed from a vector space 𝔳 endowed with an inner product 〈,〉 and an injective homomorphism ρ : 𝔳 → 𝔰𝔬(𝔳) satisfying ρ(v)v = 0 for all v ∈ 𝔳. The corresponding simply connected pseudo-Riemannian Lie groups are flat and any isometry fixing the identity element does not depend on ρ. The description allows one to construct examples starting with a compact semisimple Lie algebra and it is useful to show some applications.
CLASSIFICATION OF PM QUIVER HOPF ALGEBRAS
Authors: ZHANG SHOUCHUAN , ZHANG YAO-ZHONG , CHEN HUI-XIANG
Published: December 2007

We describe certain quiver Hopf algebras by parameters. This leads to the classification of multiple Taft algebras as well as pointed Yetter–Drinfeld modules and their corresponding Nichols algebras. In particular, when the ground-field k is the complex field and G is a finite abelian group, we classify quiver Hopf algebras over G, multiple Taft algebras over G and Nichols algebras in [Formula: see text]. We show that the quantum enveloping algebra of a complex semisimple Lie algebra is a quotient of a semi-path Hopf algebra.
H-SUPPLEMENTED DUO MODULES
Authors: KOŞAN TAMER , TÜTÜNCÜ DERYA KESKIN
Published: December 2007

Let M be a right R-module. M is called H-supplemented if for a submodule A of M there exists a direct summand D of M such that M = A + X holds if and only if M = D + X. Let M = M1 ⊕ M2 be a duo module. Then M is H-supplemented if and only if M1 and M2 are H-supplemented modules.
ON THE DERIVED LENGTH OF THE GROUP OF UNITS OF A GROUP ALGEBRA
Authors: BALOGH ZSOLT , LI YUANLIN
Published: December 2007

Let G be a group with cyclic derived subgroup of p-power order (p > 2), and F a field of characteristic p. We determine the derived length of the group of units of the group algebra FG.
A CHERN–SIMONS E8 GAUGE THEORY OF GRAVITY IN D = 15, GRAND UNIFICATION AND GENERALIZED GRAVITY IN CLIFFORD SPACES
Authors: CASTRO CARLOS
Published: December 2007

A novel Chern–Simons E8 gauge theory of gravity in D = 15 based on an octicE8 invariant expression in D = 16 (recently constructed by Cederwall and Palmkvist) is developed. A grand unification model of gravity with the other forces is very plausible within the framework of a supersymmetric extension (to incorporate spacetime fermions) of this Chern–Simons E8 gauge theory. We review the construction showing why the ordinary 11D Chern–Simons gravity theory (based on the Anti de Sitter group) can be embedded into a Clifford-algebra valued gauge theory and that an E8 Yang–Mills field theory is a small sector of a Clifford (16) algebra gauge theory. An E8 gauge bundle formulation was instrumental in understanding the topological part of the 11-dim M-theory partition function. The nature of this 11-dim E8 gauge theory remains unknown. We hope that the Chern–Simons E8 gauge theory of gravity in D = 15 advanced in this work may shed some light into solving this problem after a dimensional reduction.
MATHEMATICAL SUPPORT TO BRANEWORLD THEORY
Authors: MONTE EDMUNDO M.
Published: December 2007

The braneworld theory appear with the purpose of solving the problem of the hierarchy of the fundamental interactions. The perspectives of the theory emerge as a new physics, for example, deviation of the law of Newton's gravity. One of the principles of the theory is to suppose that the braneworld is local submanifold in a space of high dimension, the bulk, solution of Einstein's equations in high dimension. In this paper we approach the mathematical consistency of this theory with a new proof of the fundamental theorem of submanifolds for the case of semi-Riemannian manifolds. This theorem consists of an essential mathematical support for this new theory. We find the integrability conditions for the existence of space–time submanifolds in a pseudo-Euclidean space.
ON PERTURBATIONS OF MORSE HAMILTONIANS
Authors: FEDOSOV B. , ISPIRYAN T.
Published: December 2007

We give a justification of the perturbation theory for contributions of Morse critical points to the spectral decomposition in deformation quantization.
REDUCTION PROCEDURES IN CLASSICAL AND QUANTUM MECHANICS
Authors: CARIÑENA JOSÉ F. , CLEMENTE-GALLARDO JESÚS , MARMO GIUSEPPE
Published: December 2007

We present, in a pedagogical style, many instances of reduction procedures appearing in a variety of physical situations, both classical and quantum. We concentrate on the essential aspects of any reduction procedure, both in the algebraic and geometrical setting, elucidating the analogies and the differences between the classical and the quantum situations.
Animal models of human pneumonia
Authors: Mizgerd Joseph P. , Skerrett Shawn J.
Published: December 2007

Pneumonia is a medical and public health priority, and advances against this disease will require improved knowledge of biological mechanisms. Human pneumonia is modeled with experimental infections of animals, most frequently mice. Mouse models are leading to important discoveries relevant to pneumonia, but their limitations must be carefully considered. Several approaches to establishing pneumonia in mice have been developed, and each has specific strengths and weaknesses. Similarly, procedures for characterizing microbial and host responses to infection have unique advantages and disadvantages. Mice are not small humans, and the applicability of results from murine models to human disease depends on understanding the similarities and differences between species. Additional considerations such as mouse strain, microbe strain, and prior mouse-microbe interactions also influence the design and interpretation of experiments. Results from studies of pneumonia in animals, combined with complementary basic and translational studies, are elucidating mechanisms responsible for susceptibility to and pathophysiology of lung infection.
Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells
Authors: Kode Aruna , Rajendrasozhan Saravanan , Caito Samuel , Yang Se-Ran , Megson Ian L. , Rahman Irfan
Published: December 2007

Nuclear erythroid-related factor 2 (Nrf2), a redox-sensitive transcription factor, is involved in transcriptional regulation of many antioxidant genes, including glutamate-cysteine ligase (GCL). Cigarette smoke (CS) is known to cause oxidative stress and deplete glutathione (GSH) levels in alveolar epithelial cells. We hypothesized that resveratrol, a polyphenolic phytoalexin, has antioxidant signaling properties by inducing GSH biosynthesis via the activation of Nrf2 and protects lung epithelial cells against CS-mediated oxidative stress. Treatment of human primary small airway epithelial and human alveolar epithelial (A549) cells with CS extract (CSE) dose dependently decreased GSH levels and GCL activity, effects that were associated with enhanced production of reactive oxygen species. Resveratrol restored CSE-depleted GSH levels by upregulation of GCL via activation of Nrf2 and also quenched CSE-induced release of reactive oxygen species. Interestingly, CSE failed to induce nuclear translocation of Nrf2 in A549 and small airway epithelial cells. On the contrary, Nrf2 was localized in the cytosol of alveolar and airway epithelial cells due to CSE-mediated posttranslational modifications such as aldehyde/carbonyl adduct formation and nitration. On the other hand, resveratrol attenuated CSE-mediated Nrf2 modifications, thereby inducing its nuclear translocation associated with GCL gene transcription, as demonstrated by GCL-promoter reporter and Nrf2 small interfering RNA approaches. Thus resveratrol attenuates CSE-mediated GSH depletion by inducing GSH synthesis and protects epithelial cells by reversing CSE-induced posttranslational modifications of Nrf2. These data may have implications in dietary modulation of antioxidants in treatment of chronic obstructive pulmonary disease.
Amiloride-insensitive Na+and fluid absorption in the mammalian distal lung
Authors: O'Brodovich Hugh , Yang Peter , Gandhi Shephali , Otulakowski Gail
Published: December 2007

The ability of the distal lung epithelia to actively transport Na+, with Cl−and water following, from the alveolar spaces inversely correlates with morbidity and mortality of infants, children, and adults with alveolar pulmonary edema. It is now recognized, in contrast to many other Na+transporting epithelia, that at least half of this active transport is not sensitive to amiloride, which inhibits the epithelial Na+channel. This paper reviews amiloride-insensitive Na+and fluid transport in the mammalian distal lung unit under basal conditions and speculates on potential explanations for this amiloride-insensitive transport. It also provides new information, using primary cultures of rat fetal distal lung epithelia and alveolar type II cells grown under submersion and air-liquid interface culture conditions, regarding putative blockers of this transport.
A framework to identify physiological responses in microarray-based gene expression studies: selection and interpretation of biologically relevant genes
Authors: Rodenburg Wendy , Heidema A. Geert , Boer Jolanda M. A. , Bovee-Oudenhoven Ingeborg M. J. , Feskens Edith J. M. , Mariman Edwin C. M. , Keijer Jaap
Published: December 2007

In whole genome microarray studies major gene expression changes are easily identified, but it is a challenge to capture small, but biologically important, changes. Pathway-based programs can capture small effects but may have the disadvantage of being restricted to functionally annotated genes. A structured approach toward the identification of major and small changes for interpretation of biological effects is needed. We present a structured approach, a framework, that addresses different considerations in 1) the identification of informative genes in microarray data sets and 2) the interpretation of their biological relevance. The steps of this framework include gene ranking, gene selection, gene grouping, and biological interpretation. Random forests (RF), which takes gene-gene interactions into account, is examined to rank and select genes. For human, mouse, and rat whole genome arrays, less than half of the probes on the array are annotated. Consequently, pathway analysis tools ignore half of the information present in the microarray data set. The framework described takes all genes into account. RF is a useful tool to rank genes by taking interactions into account. Applying a permutation approach, we were able to define an objective threshold for gene selection. RF combined with self-organizing maps identified genes with coordinated but small gene expression responses that were not fully annotated but corresponded to the same biological process. The presented approach provides a flexible framework for biological interpretation of microarray data sets. It includes all genes in the data set, takes gene-gene interactions into account, and provides an objective threshold for gene selection.
Methods and approaches for the comprehensive characterization and quantification of cellular proteomes using mass spectrometry
Authors: Mirza Shama P. , Olivier Michael
Published: December 2007

Proteomics has been proposed as one of the key technologies in the postgenomic era. So far, however, the comprehensive analysis of cellular proteomes has been a challenge because of the dynamic nature and complexity of the multitude of proteins in cells and tissues. Various approaches have been established for the analyses of proteins in a cell at a given state, and mass spectrometry (MS) has proven to be an efficient and versatile tool. MS-based proteomics approaches have significantly improved beyond the initial identification of proteins to comprehensive characterization and quantification of proteomes and their posttranslational modifications (PTMs). Despite these advances, there is still ongoing development of new technologies to profile and analyze cellular proteomes more completely and efficiently. In this review, we focus on MS-based techniques, describe basic approaches for MS-based profiling of cellular proteomes and analysis methods to identify proteins in complex mixtures, and discuss the different approaches for quantitative proteome analysis. Finally, we briefly discuss novel developments for the analysis of PTMs. Altered levels of PTM, sometimes in the absence of protein expression changes, are often linked to cellular responses and disease states, and the comprehensive analysis of cellular proteome would not be complete without the identification and quantification of the extent of PTMs of proteins.
Crystal structure and luminescence properties of a novel promising phosphor Ba3ScB9O18
Authors: Cai Gemei , He Ming , Chen X. L. , Wang W. Y. , Lou Y. F. , Chen H. H. , Zhao J. T.
Published: December 2007

A novel borate compound
Ba3ScB9O18 has been synthesized by solid-state reaction and its structure has been determined and refined from powder X-ray diffraction data. This compound crystallizes in a hexagonal cell (space group P63/m) with lattice parameters a=7.1360(4) Å and c=16.5420(9) Å, and each unit cell contains two formulas. Its crystal structure is made up of planar
B3O6 groups parallel to each other along the [001] direction, regular
ScO6 octahedra, irregular
BaO6 hexagons, and BaO9 polyhedra to form an analogue structure of
Ba3YB9O18. DTA and TGA curves for
Ba3ScB9O18 show that it is a chemically stable and congruent melting compound. Luminescence properties for Ba3ScB9O18 were investigated using fluorescence spectroscopy and X-ray excited luminescence measurements. Its emission spectrum upon UV excitation (330 nm) has exhibited a prominent blue-green emission band at about 490 nm, and its XEL spectra show an intense emission band in the range of 360 to 500 nm with peak center at 400 nm. The light yield of
Ba3ScB9O18 powders is about 23% as large as that of BGO powders under the same measurement conditions. There seems to be a certain relationship between the scintillation properties and the structural features of
Ba3ScB9O18.
Study of a chemical-vapor-deposited diamond thin film on a molybdenum substrate by glancing incidence X-ray diffraction
Authors: Fang Jianfeng , Huo Jing , Zhang Jinyuan , Zheng Yi
Published: December 2007

The structure of a chemical-vapor-deposited (CVD) diamond thin film on a Mo substrate was studied using quasi-parallel X-ray and glancing incidence techniques. Conventional X-ray diffraction analysis revealed that the sample consists of a diamond thin film, a
Mo2C
transition layer, and Mo substrate. The
Mo2C
transition layer was formed by a chemical reaction between the diamond film and the Mo substrate during the CVD process. A method for layer-thickness determination of the thin film and the transition layer was developed. This method was based on a relationship between X-ray diffraction intensities from the transition layer or its substrate and a function of grazing incidence angles. Results of glancing incidence X-ray diffraction analysis showed that thicknesses of the diamond thin film and the
Mo2C
transition layer were determined successfully with high precision.
Qualitative and quantitative phase analyses of Pingguo bauxite mineral using X-ray powder diffraction and the Rietveld method
Authors: Nong Liangqin , Yang Xiying , Zeng Lingmin , Liu Jingping
Published: December 2007

X-ray powder diffraction technique and the Rietveld refinement method have been used successfully for the qualitative and quantitative analyses of Pingguo bauxite from Guangxi, China. Qualitative phase analysis shows that the Pingguo bauxite contains diaspore (AlOOH), hematite (Fe2O3), goethite (FeOOH), anatase (TiO2), and kaolinite (Al2(Si2O5)(OH)4). Quantitative Rietveld refinement shows that the weight concentrations of diaspore, goethite, hematite, anatase, and kaolinite for the Pingguo bauxite are 71.9(4)%, 7.0(8)%, 11.3(7)%, 6.5(6)%, and 3.3(9)%, respectively.
Structure of a new compound KBaB5O9 and photoluminescence characteristics of KBaB5O9:Eu3+
Authors: Sun Y. P. , Du Yinxiao , Wang W. Y. , He Ming , Cai G. M. , Chen X. L.
Published: December 2007

Crystal structure of a new compound
KBaB5O9 has been investigated from X-ray powder diffraction data. This compound is isostructural with
KSrB5O9 and crystallizes in the monoclinic system with space group P21/c. Unit-cell parameters are a=6.7200(2) Å, b=8.3256(2) Å, c=14.3674(4) Å, and β=92.6103(3) deg. Its structure contains both
B3O7 and
B3O8 rings, which share a common B atom to form a complex two dimensional network constituting the basic
B5O9 unit in the formula. Adjacent networks are bound together by Ba and K atoms, which have eight- and nine-coordinate sites, respectively. In addition, DTA and TGA curves reveal that
KBaB5O9 decomposes at 798 °C. Photoluminescence (PL) characteristics of
KBaB5O9:Eu3+ have been studied. The PL spectra show the strongest emission at 618 nm and the quench concentration of Eu3+ is 4 at. %.
Proarrhythmic Aspects of Atrial Fibrillation Surgery
Authors: McElderry H. Thomas , McGiffin David C. , Plumb Vance J. , Nanthakumar Kumaraswamy , Epstein Andrew E. , Yamada Takumi , Kay G. Neal
Published: December 2007

Background—

Surgery for the treatment of atrial fibrillation may be associated with early or late postoperative atrial arrhythmias. In many cases, the arrhythmias that occur early in the postoperative course may be related to pericardial inflammation or increased catecholamine levels and tend to resolve without further therapy. In contrast, late postoperative arrhythmias often are persistent, highly symptomatic, and refractory to medical therapy. The incidence and mechanisms of these late atrial arrhythmias have not been thoroughly described.

Methods and Results—

In this study, a total of 143 consecutive patients undergoing atrial fibrillation surgery from 1996 to 2005 were prospectively followed up. Sustained atrial tachycardia developed in 22 of 143 patients (15%) >8 weeks after the surgical procedure. These patients underwent electrophysiological study. A total of 25 separate tachycardias were mapped in these 22 patients, including 15 located in right atrium and 10 in the left atrium. Right atrial tachycardias included cavotricuspid isthmus–dependent atrial flutter (n=7), non–isthmus-dependent right atrial reentry (n=7), and 1 focal atrial tachycardia. Left atrial tachycardias included reentry around the mitral valve (n=3) and in the roof of the left atrium (n=7). All tachycardias were successfully treated with radiofrequency catheter ablation with no recurrences in long-term follow-up.

Conclusions—

Postoperative arrhythmias are not uncommon late after surgery for atrial fibrillation and typically are reentrant and related to surgically created boundaries. Radiofrequency catheter ablation is highly effective in the management of these late arrhythmias.
High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome
Authors: Mahmoodi Bakhtawar K. , ten Kate Min Ki , Waanders Femke , Veeger Nic J.G.M. , Brouwer Jan-Leendert P. , Vogt Liffert , Navis Gerjan , van der Meer Jan
Published: December 2007

Background—

No data are available on the absolute risk of either venous thromboembolism (VTE) or arterial thromboembolism (ATE) in patients with nephrotic syndrome. Reported risks are based on multiple case reports and small studies with mostly short-term follow-up. We assessed the absolute risk of VTE and ATE in a large, single-center, retrospective cohort study and attempted to identify predictive factors in these patients.

Methods and Results—

A total of 298 consecutive patients with nephrotic syndrome (59% men; mean age, 42±18 years) were enrolled. Mean follow-up was 10±9 years. Nephrotic syndrome was defined by proteinuria ≥3.5 g/d, and patients were classified according to underlying histological lesions accounting for nephrotic syndrome. Objectively verified symptomatic thromboembolic events were the primary study outcome. Annual incidences of VTE and ATE were 1.02% (95% confidence interval, 0.68 to 1.46) and 1.48% (95% confidence interval, 1.07 to 1.99), respectively. Over the first 6 months of follow-up, these rates were 9.85% and 5.52%, respectively. Proteinuria and serum albumin levels tended to be related to VTE; however, only the predictive value of the ratio of proteinuria to serum albumin was significant (hazard ratio, 5.6; 95% confidence interval, 1.2 to 26.2;
P
=0.03). In contrast, neither the degree of proteinuria nor serum albumin levels were related to ATE. Sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate predicted ATE (
P
≤0.02).

Conclusions—

This study verifies high absolute risks of symptomatic VTE and ATE that were remarkably elevated within the first 6 months. Whereas the ratio of proteinuria to serum albumin predicted VTE, estimated glomerular filtration rate and multiple classic risk factors for atherosclerosis were predictors of ATE.
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms
Authors: Nishimura Masaki , Izumiya Yasuhiro , Higuchi Akiko , Shibata Rei , Qiu Jianhua , Kudo Chiho , Shin Hwa Kyoung , Moskowitz Michael A. , Ouchi Noriyuki
Published: December 2007

Background—

Adiponectin is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. A low level of plasma adiponectin is associated with increased mortality after ischemic stroke; however, the causal role of adiponectin in ischemic stroke is unknown.

Methods and Results—

To explore the role of adiponectin in the development of acute cerebral injury, we subjected adiponectin-deficient (APN-KO) and wild-type (WT) mice to 1 hour of middle cerebral artery occlusion followed by 23 hours of reperfusion. APN-KO mice exhibited enlarged brain infarction and increased neurological deficits after ischemia-reperfusion compared with WT mice. Conversely, adenovirus-mediated supplementation of adiponectin significantly reduced cerebral infarct size in WT and APN-KO mice. APN-KO mice showed decreased cerebral blood flow during ischemia by laser speckle flowmetry methods. Adiponectin colocalized within the cerebral vascular endothelium under transient ischemic conditions by immunohistochemical analysis. Phosphorylation of endothelial nitric oxide synthase in ischemic brain tissues and the production of nitric oxide metabolites in plasma were attenuated in APN-KO mice compared with WT mice. Adenovirus-mediated administration of adiponectin stimulated endothelial nitric oxide synthase phosphorylation and nitric oxide metabolites during cerebral ischemia in both WT and APN-KO mice. Neuronal nitric oxide synthase expression during ischemia did not differ between WT and APN-KO mice. Adenovirus-mediated delivery of adiponectin did not affect brain infarction in mice deficient in endothelial nitric oxide synthase.

Conclusions—

These data provide causal evidence that adiponectin exerts a cerebroprotective action through an endothelial nitric oxide synthase–dependent mechanism. Adiponectin could represent a molecular target for the prevention of ischemic stroke.
Dietary α-Lipoic Acid Supplementation Inhibits Atherosclerotic Lesion Development in Apolipoprotein E–Deficient and Apolipoprotein E/Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Zhang Wei-Jian , Bird Karyn E. , McMillen Timothy S. , LeBoeuf Renee C. , Hagen Tory M. , Frei Balz
Published: December 2007

Background—

Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound α-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-α– and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo. Here, we investigated whether LA inhibits atherosclerosis in apolipoprotein E–deficient (apoE
−/−
) and apoE/low-density lipoprotein receptor–deficient mice, 2 well-established animal models of human atherosclerosis.

Methods and Results—

Four-week–old female apoE
−/−
mice (n=20 per group) or apoE/low-density lipoprotein receptor–deficient mice (n=21 per group) were fed for 10 weeks a Western-type chow diet containing 15% fat and 0.125% cholesterol without or with 0.2% (wt/wt)
R,S
-LA or a normal chow diet containing 4% fat without or with 0.2% (wt/wt)
R
-LA, respectively. Supplementation with LA significantly reduced atherosclerotic lesion formation in the aortic sinus of both mouse models by ≈20% and in the aortic arch and thoracic aorta of apoE
−/−
and apoE/low-density lipoprotein receptor–deficient mice by ≈55% and 40%, respectively. This strong antiatherogenic effect of LA was associated with almost 40% less body weight gain and lower serum and very low-density lipoprotein levels of triglycerides but not cholesterol. In addition, LA supplementation reduced aortic expression of adhesion molecules and proinflammatory cytokines and aortic macrophage accumulation. These antiinflammatory effects of LA were more pronounced in the aortic arch and the thoracic aorta than in the aortic sinus, reflecting the corresponding reductions in atherosclerosis.

Conclusions—

Our study shows that dietary LA supplementation inhibits atherosclerotic lesion formation in 2 mouse models of human atherosclerosis, an inhibition that appears to be due to the “antiobesity,” antihypertriglyceridemic, and antiinflammatory effects of LA. LA may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases.