bluuebunny/crossref_metadata_2025 huggingface dataset:
What is Said, Linguistic Meaning, and Directly Referential Expressions
Authors: Stojanovic Isidora
Published: June 2006

Philosophers of language generally distinguish among the lexical or linguistic meaning of the sentence uttered, what is said by an utterance of the sentence, and speaker’s meaning, or what is conveyed by the speaker to her audience. In most views, what is said is the semantic or truth‐conditional content of the utterance, and is irreducible either to the linguistic meaning or to the speaker’s meaning. I will show that those views account badly for people’s intuitions on what is said. I will also argue that no distinguished level of what is said is required, and that the notion of linguistic meaning is best placed to play the role of what is said. This relies on two (possibly controversial) points. First, our intuitions on what is said cannot be detached from the ways in which we talk about what is said, and from the semantics of speech reports and indirect discourse in general. Second, beside what is said, there is an equally important notion of what what‐is‐said is said about, or that about which the speaker is talking. Here are, then, the three ingredients needed for the theory of what is said: linguistic meaning, what is talked about, and the semantics of reported speech.
Two Dogmas of Neo‐Empiricism
Authors: Machery Edouard
Published: June 2006

This article critically examines the contemporary resurgence of empiricism (or “neo‐empiricism”) in philosophy, psychology, neuropsychology, and artificial intelligence. This resurgence is an important and positive development. It is the first time that this centuries‐old empiricist approach to cognition is precisely formulated in the context of cognitive science and neuroscience. Moreover, neo‐empiricists have made several findings that challenge amodal theories of concepts and higher cognition. It is argued, however, that the theoretical foundations of and the empirical evidence for neo‐empiricism are not as strong as is usually claimed by its proponents. The empirical evidence for and against neo‐empiricism is discussed in detail.
Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans
Authors: Otsuki T. , Maeda S. , Iemitsu M. , Saito Y. , Tanimura Y. , Ajisaka R. , Miyauchi T.
Published: June 2006

Background:  Effective arterial elastance (Ea), an index of arterial load, increases with elevations in left ventricular elastance to maximize the efficiency of left ventricular stroke work during exercise. Systemic arterial compliance (C) and vascular resistance (R) are the primary components contributing to Ea, and R plays a greater role in determining Ea at rest. We hypothesized that the contribution of C to Ea increases during exercise to maintain an optimal balance between arterial load and ventricular elastance, and that the increase in Ea is due primarily to a reduction in C.

Aim:  The aim of this study was to investigate the contributions of C and R to Ea during exercise.

Methods:  Ea (0.9 × systolic blood pressure/stroke volume), C (stroke volume/pulse pressure), R (mean blood pressure/cardiac output), and cardiac cycle length (T) were measured at rest and during exercise of 40%, 60% and 80% maximal oxygen uptake (O2max) using Doppler echocardiography in 45 healthy men.

Results:  Ea did not differ between rest and 40%O2max, but it was greater at 60% and 80%O2max. C markedly decreased during exercise in an exercise intensity‐dependent manner. The changes in R/T during exercise were small, whereas it decreased at 40%O2max and gradually increased at 60% and 80%O2max.

Conclusions:  The present results suggest that the contribution of systemic arterial compliance to effective arterial elastance increases during exercise. Therefore, we propose that the increase in arterial load during exercise is mainly driven by a reduction in systemic arterial compliance.
Loading rat heart myocytes with Mg2+ using low‐[Na+] solutions
Authors: Almulla Hasan A. , Bush Peter G. , Steele Michael G. , Ellis David , Flatman Peter W.
Published: June 2006

The objective of our study was to investigate how Mg2+ enters mammalian cardiac cells. During this work, we found evidence for a previously undescribed route for Mg2+ entry, and now provide a preliminary account of its properties. Changes in Mg2+ influx into rat ventricular myocytes were deduced from changes in intracellular ionized Mg2+ concentration ([fMg2+]i) measured from the fluorescence of mag‐fura‐2 loaded into isolated cells. Superfusion of myocytes at 37°C with Ca2+‐free solutions with both reduced [Na+] and raised [Mg2+] caused myocytes to load with Mg2+. Uptake was seen with solutions containing 5 mm Mg2+ and 95 mm Na+, and increased linearly with increasing extracellular [Mg2+] or decreasing extracellular [Na+]. It was very sensitive to temperature (Q10 > 9, 25‐‐37°C), was observed even in myocytes with very low Na+ contents, and stopped abruptly when external [Na+] was returned to normal. Uptake was greatly reduced by imipramine or KB‐R7943 if these were added when [fMg2+]i was close to the physiological level, but was unaffected if they were applied when [fMg2+]i was above 2 mm. Uptake was also reduced by depolarizing the membrane potential by increasing extracellular [K+] or voltage clamp to 0 mV. We suggest that initial Mg2+ uptake may involve several transporters, including reversed Na+–Mg2+ antiport and, depending on the exact conditions, reversed Na+–Ca2+ antiport. The ensuing rise of [fMg2+]i, in conjunction with reduced [Na+], may then activate a new Mg2+ transporter that is highly sensitive to temperature, is insensitive to imipramine or KB‐R7943, but is inactivated by depolarization.
High throughput protein expression screening in the nervous system – needs and limitations
Authors: Anderson Chris N. G. , Grant Seth G. N.
Published: June 2006

The cellular complexity of the brain (some estimate that there are up to 103 different cell types) is exceeded by the synaptic complexity, with each of the ∼1011 neurons in the brain having around 103–104 synapses. Proteomic studies of the synapse have revealed that the postsynaptic density is the most complex multiprotein structure yet identified, with ∼103 different proteins. Such studies, however, use brain tissue with many different regions and therefore different cell types, and there is clear potential for heterogeneity of protein content at different synapses within and between brain regions. Although large‐scale mRNA‐based assays are in progress to map this sort of complexity at the cellular level, and indeed all brain‐expressed genes, analysis of protein distribution (at synapses and other structures) is still in the very early stages. We review existing large‐scale protein expression studies and the specific technical obstacles that need to be overcome before applying the scaling used in nucleic acid based approaches.
Nonlinear Mechanics of Solids Containing Isolated Voids
Authors: Huang Z. P. , Wang J.
Published: June 2006

The ductile fracture of many materials is related to the nucleation, growth, and coalescence of voids. Also, a material containing voids represents an extreme case of heterogeneous materials. In the last few decades, numerous studies have been devoted to the local deformation mechanisms and macroscopic overall properties of nonlinear materials containing voids. This article presents a critical review of the studies in three interconnected topics in nonlinear mechanics of materials containing isolated voids, namely, the growth of an isolated void in an infinite medium under a remote stress; the macroscopic mechanical behavior of these materials predicted by using a cell model; and bounds and estimates of the overall properties of these materials as a special case of nonlinear composite materials. Emphasis are placed upon analytical and semianalytical approaches for static loading conditions. Both the classical methods and more recent approaches are examined, and some inadequacies in the existing methods are pointed out. In addition to the critical review of the existing methods and results, some new results, including a power-law stress potential for compressible nonlinear materials, are presented and integrated into the pertinent theoretical frameworks. This review article contains 118 references.
Nonlinear Stochastic Dynamics and Control in Hamiltonian Formulation
Authors: Zhu W. Q.
Published: June 2006

The significant advances in nonlinear stochastic dynamics and control in Hamiltonian formulation during the past decade are reviewed. The exact stationary solutions and equivalent nonlinear system method of Gaussian-white -noises excited and dissipated Hamiltonian systems, the stochastic averaging method for quasi Hamiltonian systems, the stochastic stability, stochastic bifurcation, first-passage time and nonlinear stochastic optimal control of quasi Hamiltonian systems are summarized. Possible extension and applications of the theory are pointed out. This review article cites 158 references.
TRB3 Links the E3 Ubiquitin Ligase COP1 to Lipid Metabolism
Authors: Qi Ling , Heredia Jose E. , Altarejos Judith Y. , Screaton Robert , Goebel Naomi , Niessen Sherry , MacLeod Ian X. , Liew Chong Wee , Kulkarni Rohit N. , Bain James , Newgard Christopher , Nelson Michael , Evans Ronald M. , Yates John , Montminy Marc
Published: June 2006

During fasting, increased concentrations of circulating catecholamines promote the mobilization of lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl–coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. Here, we describe a parallel pathway, in which the pseudokinase Tribbles 3 (TRB3), whose abundance is increased during fasting, stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3 promoted ACC ubiquitination through an association with the E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.
JETLAG Resets the
Drosophila
Circadian Clock by Promoting Light-Induced Degradation of TIMELESS
Authors: Koh Kyunghee , Zheng Xiangzhong , Sehgal Amita
Published: June 2006

Organisms ranging from bacteria to humans synchronize their internal clocks to daily cycles of light and dark. Photic entrainment of the
Drosophila
clock is mediated by proteasomal degradation of the clock protein TIMELESS (TIM). We have identified mutations in
jetlag
—a gene coding for an F-box protein with leucine-rich repeats—that result in reduced light sensitivity of the circadian clock. Mutant flies show rhythmic behavior in constant light, reduced phase shifts in response to light pulses, and reduced light-dependent degradation of TIM. Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in cultured S2R cells confers light-dependent degradation onto TIM, thereby reconstituting the acute response + of the circadian clock to light in a cell culture system. Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM.
Comment on "Nature of Phosphorus Limitation in the Ultraoligotrophic Eastern Mediterranean"
Authors: Hale Michelle S. , Rivkin Richard B.
Published: June 2006

Thingstad
et al
. (Reports, 12 August 2005, p. 1068) reported that in situ mesoscale phosphorus enrichment of the eastern Mediterranean Sea altered selected biological parameters and concluded that the added phosphorus was rapidly transferred from bacteria to mesozooplankton. However, because of a lack of replication and a misinterpretation of their statistical analyses, that conclusion is not supported by the data.
Response to Comment on "Nature of Phosphorus Limitation in the Ultraoligotrophic Eastern Mediterranean"
Authors: Thingstad T. F. , Law C. S. , Krom M. D. , Mantoura R. F. C. , Pitta P. , Psarra S. , Rassoulzadegan F. , Tanaka T. , Wassmann P. , Riser C. Wexels , Zohary T.
Published: June 2006

With no requirement for synoptic treated (IN) and control (OUT) stations, analysis of covariance is an interesting statistical technique for testing IN-OUT differences in Lagrangian experiments, but it has inherent limitations due to its assumption of linear responses. With this limitation properly considered, we find that analysis of covariance strengthens, not weakens, experimental support for the food-web transfer mechanisms we proposed.
Early Cretaceous Spider Web with Its Prey
Authors: Peñalver Enrique , Grimaldi David. A. , Delclòs Xavier
Published: June 2006

Araneoid spiders are renowned for their efficient capture of flying insects with intricate aerial webs. Origins of this web structure are obscure, however, because they rarely fossilize. Reported here is an exceptional situation of insects trapped in part of a gummy aerial web preserved in a runnel of amber from Spain that is ~110 million years old (Early Cretaceous). This is the oldest direct evidence of a spider web made by Araneoidea and of its use for predation. Thus, the interception of flying insects by spiders has a minimum age coinciding with the explosive diversification of the angiosperms and of major pollinating groups of insects.
The Muscle Protein Dok-7 Is Essential for Neuromuscular Synaptogenesis
Authors: Okada Kumiko , Inoue Akane , Okada Momoko , Murata Yoji , Kakuta Shigeru , Jigami Takafumi , Kubo Sachiko , Shiraishi Hirokazu , Eguchi Katsumi , Motomura Masakatsu , Akiyama Tetsu , Iwakura Yoichiro , Higuchi Osamu , Yamanashi Yuji
Published: June 2006

The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK.
A Topoisomerase IIß-Mediated dsDNA Break Required for Regulated Transcription
Authors: Ju Bong-Gun , Lunyak Victoria V. , Perissi Valentina , Garcia-Bassets Ivan , Rose David W. , Glass Christopher K. , Rosenfeld Michael G.
Published: June 2006

Multiple enzymatic activities are required for transcriptional initiation. The enzyme DNA topoisomerase II associates with gene promoter regions and can generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to know whether this enzyme is critical for regulated gene activation. We report that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase IIβ-dependent, transient, site-specific dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate–ribose) polymerase–1 enzymatic activity is induced, which is required for a nucleosome-specific histone H1–high-mobility group B exchange event and for local changes of chromatin architecture. Our data mechanistically link DNA topoisomerase IIβ–dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription.
Costly Punishment Across Human Societies
Authors: Henrich Joseph , McElreath Richard , Barr Abigail , Ensminger Jean , Barrett Clark , Bolyanatz Alexander , Cardenas Juan Camilo , Gurven Michael , Gwako Edwins , Henrich Natalie , Lesorogol Carolyn , Marlowe Frank , Tracer David , Ziker John
Published: June 2006

Recent behavioral experiments aimed at understanding the evolutionary foundations of human cooperation have suggested that a willingness to engage in costly punishment, even in one-shot situations, may be part of human psychology and a key element in understanding our sociality. However, because most experiments have been confined to students in industrialized societies, generalizations of these insights to the species have necessarily been tentative. Here, experimental results from 15 diverse populations show that (i) all populations demonstrate some willingness to administer costly punishment as unequal behavior increases, (ii) the magnitude of this punishment varies substantially across populations, and (iii) costly punishment positively covaries with altruistic behavior across populations. These findings are consistent with models of the gene-culture coevolution of human altruism and further sharpen what any theory of human cooperation needs to explain.
Silk Genes Support the Single Origin of Orb Webs
Authors: Garb Jessica E. , DiMauro Teresa , Vo Victoria , Hayashi Cheryl Y.
Published: June 2006

The orb web is a spectacular evolutionary innovation that enables spiders to catch flying prey. This elegant, geometric structure is woven with silk fibers that are renowned for their superior mechanical properties. We used silk gland expression libraries to address a long-standing controversy concerning the evolution of the orb-web architecture. Contrary to the view that the orb-web design evolved multiple times, we found that the distribution and phylogeny of silk proteins support a single, ancient origin of the orb web at least 136 million years ago. Furthermore, we substantially expanded the repository of silk sequences that can be used for the synthesis of high-performance biomaterials.
Depletion, Degradation, and Recovery Potential of Estuaries and Coastal Seas
Authors: Lotze Heike K. , Lenihan Hunter S. , Bourque Bruce J. , Bradbury Roger H. , Cooke Richard G. , Kay Matthew C. , Kidwell Susan M. , Kirby Michael X. , Peterson Charles H. , Jackson Jeremy B. C.
Published: June 2006

Estuarine and coastal transformation is as old as civilization yet has dramatically accelerated over the past 150 to 300 years. Reconstructed time lines, causes, and consequences of change in 12 once diverse and productive estuaries and coastal seas worldwide show similar patterns: Human impacts have depleted >90% of formerly important species, destroyed >65% of seagrass and wetland habitat, degraded water quality, and accelerated species invasions. Twentieth-century conservation efforts achieved partial recovery of upper trophic levels but have so far failed to restore former ecosystem structure and function. Our results provide detailed historical baselines and quantitative targets for ecosystem-based management and marine conservation.
Middle Paleolithic Shell Beads in Israel and Algeria
Authors: Vanhaeren Marian , d'Errico Francesco , Stringer Chris , James Sarah L. , Todd Jonathan A. , Mienis Henk K.
Published: June 2006

Perforated marine gastropod shells at the western Asian site of Skhul and the North African site of Oued Djebbana indicate the early use of beads by modern humans in these regions. The remoteness of these sites from the seashore and a comparison of the shells to natural shell assemblages indicate deliberate selection and transport by humans for symbolic use. Elemental and chemical analyses of sediment matrix adhered to one
Nassarius gibbosulus
from Skhul indicate that the shell bead comes from a layer containing 10 human fossils and dating to 100,000 to 135,000 years ago, about 25,000 years earlier than previous evidence for personal decoration by modern humans in South Africa.
Building on Shaken Ground
Authors: Stewart Iain
Published: June 2006

Earthquake Nation
. The Cultural Politics of Japanese Seismicity, 1868-1930.
By Gregory Clancey
. University of California Press, Berkeley, CA, 2006. 345 pp. $49.95, £32.50. ISBN 0-520-24607-1.

The author explores the development of seismology and quake-resistant engineering along with their cultural and political ramifications in Japan between the Meiji Restoration and the 1923 earthquake that destroyed Tokyo.
Synthesis of Bromophenyl β-D-Glucuronides: Hydrophilic Precursors of Lipophilic Standards in the Analysis of Environmental Polychlorinated Biphenyls
Authors: Tandon Manju , Kumar Piyush , Xia Haiyan , Wang Lili , Wiebe Leonard I.
Published: June 2006

A rapid PCB-screening protocol, based on a combination of extraction techniques and instrumental nuclear activation analysis (INAA), required water soluble brominated internal standard that undergoes facile hydrolysis to a lipophilic brominated counterpart. Bromophenyl glucuronic acids 2, 3, 7 were synthesized for this application. Glucuronic acids 2 and 3 were prepared by bromination of phenyl β-D-glucopyranosiduronic acid in 81 and 54%, respectively, whereas compound 7 was prepared by coupling methyl 2,3,4-tri-O-acetyl-α-D-glucopyranosyluronate bromide (5) with 2,4,6-tribromophenol. Incubation with β-glucuronidase indicated that tribromophenyl derivative 7 is an excellent substrate, with near quantitative conversion to tribromophenol within seconds of incubation with the enzyme.
Validity of the inexpensive Stepping Meter in counting steps in free living conditions: a pilot study
Authors: De Cocker K , Cardon G , De Bourdeaudhuij I
Published: June 2006

Objectives:To evaluate if inexpensive Stepping Meters are valid in counting steps in adults in free living conditions.

Methods:For six days, 35 healthy volunteers wore a criterion Yamax Digiwalker and five Stepping Meters every day until all 973 pedometers had been tested. Steps were recorded daily, and the differences between counts from the Digiwalker and the Stepping Meter were expressed as a percentage of the valid value of the Digiwalker step counts. The criterion used to determine if a Stepping Meter was valid was a maximum deviation of 10% from the Digiwalker step counts.

Results:A total of 252 (25.9%) Stepping Meters met the criterion, whereas 74.1% made an overestimation or underestimation of more than 10%. In more than one third (36.6%) of the invalid Stepping Meters, the deviation was greater than 50%. Most (64.8%) of the invalid pedometers overestimated the actual steps taken.

Conclusions:Inexpensive Stepping Meters cannot be used in community interventions as they will give participants the wrong message.
Surgical treatment of partial tears of the proximal origin of the hamstring muscles
Authors: Lempainen L , Sarimo J , Heikkilä J , Mattila K , Orava S
Published: June 2006

Background:Hamstring injuries are common especially in athletes. Partial and complete tears of the proximal origin may cause pain and functional loss.

Objective:To evaluate the results of surgical treatment for partial proximal hamstring tears.

Methods:Between 1994 and 2005, 47 athletes (48 cases, 1 bilateral) with partial proximal hamstring tears were operated on. The cases were retrospectively analysed. Before surgery, 42 of the patients had undergone conservative treatment with unsatisfactory results, whereas in five patients the operation was performed within four weeks of the injury.

Results:The mean length of the follow up was 36 months (range 6–72). The result of the operation was rated excellent in 33 cases, good in nine, fair in four, and poor in two. Forty one patients were able to return to their former level of sport after an average of five months (range 1–12).

Conclusion:In most cases, excellent or good results can be expected after surgical repair of partial proximal hamstring tears even after conservative treatment has failed.
Chromosome 6p amplification and cancer progression
Authors: Santos Gda C , Zielenska M , Prasad M , Squire J A
Published: June 2006

Chromosomal imbalances represent an important mechanism in cancer progression. A clear association between DNA copy-number aberrations and prognosis has been found in a variety of tumours. Comparative genomic hybridisation studies have detected copy-number increases affecting chromosome 6p in several types of cancer. A systematic analysis of large tumour cohorts is required to identify genomic imbalances of 6p that correlate with a distinct clinical feature of disease progression. Recent findings suggest that a central part of the short arm of chromosome 6p harbours one or more oncogenes directly involved in tumour progression. Gains at 6p have been associated with advanced or metastatic disease, poor prognosis, venous invasion in bladder, colorectal, ovarian and hepatocellular carcinomas. Copy number gains of 6p DNA have been described in a series of patients who presented initially with follicle centre lymphoma, which subsequently transformed to diffuse large B cell lymphoma. Melanoma cytogenetics has consistently identified aberrations of chromosome 6, and a correlation with lower overall survival has been described. Most of the changes observed in tumours to date map to the 6p21–p23 region, which encompasses approximately half of the genes on all of chromosome 6 and one third of the number of CpG islands in this chromosome. Analyses of the genes that cluster to the commonly amplified regions of chromosome 6p have helped to identify a small number of molecular pathways that become deregulated during tumour progression in diverse tumour types. Such pathways offer promise for new treatments in the future.
Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI, cystatin A) in non-small-cell lung cancer
Authors: Leinonen T , Pirinen R , Böhm J , Johansson R , Rinne A , Weber E , Kosma V-M
Published: June 2006

Background:Acid cysteine protease inhibitor (ACPI) is an intracellular protein, often linked to neoplastic changes in epithelium and thought to have an inhibitory role in malignant transformation.

Aim:To analyse the expression and prognostic role of ACPI in non-small-cell lung cancer (NSCLC).

Method:Histological samples from 199 patients with resected NSCLC were stained immunohistochemically for the expression of ACPI in normal and preneoplastic bronchial epithelium, and in various types of lung carcinomas.

Results:A normal bronchial epithelium showed positive staining for ACPI in the basal cells, whereas the upper two-thirds of the dysplastic epithelium was ACPI positive. High staining for ACPI was found in 74% (91/123) of squamous-cell carcinomas, whereas 16% (8/49) of adenocarcinomas and 30% of (8/27) large-cell carcinomas showed the high expression of ACPI (p<0.001). Among squamous-cell carcinomas, low expression of ACPI was correlated with poor tumour differentiation (p = 0.032). In the whole tissue, reduced expression of ACPI was associated with tumour recurrence (p = 0.024). In overall survival (OS) and disease-free survival (DFS) analyses, the histological type of the tumour (both p<0.001) and stage of the tumour (p = 0.001, p = 0.013, respectively) were related to patient outcome. Low expression of ACPI in tumour cells was associated with poor OS and DFS (p<0.041, p = 0.004, respectively). In multivariate analysis, ACPI did not retain its prognostic value, whereas the traditional factors were the most important prognostic factors.

Conclusions:ACPI expression is linked with the malignant transformation of the bronchial epithelium and predicts a risk of tumour recurrence as well as poor rate of survival for the patients. However, ACPI does not have any independent prognostic value in NSCLC.
C-reactive protein in vulnerable coronary plaques
Authors: Norja Silja , Nuutila Lauri , Karhunen Pekka J , Goebeler Sirkka
Published: June 2006

Background:An increased level of serum C-reactive protein (CRP) is a known prognostic factor for acute coronary events and sudden cardiac death, and it is associated with coronary calcification. CRP is expressed in coronary arteries, but its role in the development of coronary plaques is unclear.

Aim:To investigate CRP immunoreactivity in relation to the severity of coronary artery disease and plaque morphology in human left anterior descending coronary arteries (LAD).

Methods:A prospective, consecutive autopsy series of 66 patients (mean age 63.4 years) in Tampere University Hospital, Tampere, Finland.

Results:CRP immunoreactivity was seen in 59% of the cases. In logistic regression analysis with age, sex and body mass index as confounders, CRP immunoreactivity in LAD was associated with >50% stenosis and plaque calcification. All three cases with acute coronary thrombosis due to rupture or erosion of the plaque showed a clear immunopositive reaction. CRP-positive cells were never detected in normal arteries, but were often found in early fibrous plaques (75%) and almost invariably present in the shoulder area of plaques with necrotic core (96%). CRP immunoreactivity adjacent to calcified areas in more stable plaques (71%) was less consistent with one-third of these plaques showing no immunoreactivity.

Conclusions:CRP immunoreactivity is associated with the progression of atherosclerosis, and especially with unstable coronary plaques. The immunoreactivity could cease at the stable calcified stages of atherosclerosis.
STABILITY AND MULTIPLICITY OF PERIODIC OR ALMOST PERIODIC SOLUTIONS TO SCALAR FIRST-ORDER ODE
Authors: HARAUX ALAIN
Published: June 2006

Using a monotonicity property specific to this case, we give a general property of the stability pattern of successive periodic solutions of the first-order scalar differential equation u′ = f(t, u). We also give an optimal smallness condition in order for the quasi-autonomous equation u′+g(u) = f(t) where g ∈ C1(ℝ) and f : ℝ → ℝ is almost periodic to have exactly N almost periodic solutions on the line assuming that we have exactly N equilibria ci and g′(ci) ≠ 0 for all i.
UNIQUE SOLUTIONS OF DISCONTINUOUS O.D.E.'S IN BANACH SPACES
Authors: BRESSAN ALBERTO , SHEN WEN
Published: June 2006

We consider the Cauchy problem for an ordinary differential equation with discontinuous right-hand side in an L∞ space. Under the assumptions that the vector field is directionally continuous with bounded directional variation, we prove that the O.D.E. has a unique Carathéodory solution, which depends Lipschitz continuously on the data.
THE BOLTZMANN EQUATION IN THE SPACE $L^2\cap L^\infty_\beta$: GLOBAL AND TIME-PERIODIC SOLUTIONS
Authors: UKAI SEIJI , YANG TONG
Published: June 2006

We present a function space in which the Cauchy problem for the Boltzmann equation is well-posed globally in time near an absolute Maxwellian in a mild sense without any regularity conditions. The asymptotic stability of the absolute Maxwellian is also established in this space and, moreover, it is shown that the higher order spatial derivatives of the solutions vanish in time faster than the lower order derivatives. No smallness assumptions are imposed on the derivatives of the initial data, and the optimal decay rates are derived. Furthermore, the Boltzmann equation with a time-periodic source term is solved in the same space on the unique existence and stability of a time-periodic solution which has the same period as the source term. The proof is based on the spectral analysis of the linearized Boltzmann operator.
LIE–LAGRANGIAN MODEL FOR REALISTIC HUMAN BIODYNAMICS
Authors: IVANCEVIC VLADIMIR
Published: June 2006

We present a sophisticated Lagrangian model for anatomically and physiologically realistic human biodynamics (RHB), to accompany the recently reported Hamiltonian formulation.1 The present RHB formulation is designed around three main modules: (i) A Riemannian configuration manifold, composed of gauge Lie groups of constrained 3D rotations and translations, which includes more than 300 degrees of freedom (DOF); (ii) exterior Lagrangian dynamics of the human musculo-skeletal system, including all natural conservative, dissipative and driving forces, powered by 600 equivalent muscles; and (iii) hierarchical nonlinear control, based on an iterative Lie derivative formalism, resembling both spinal reflexes and coordination-control of the human cerebellum.

RHB is driven by individual, user supplied musculo-skeletal data. It is modeled in the computer algebra system Mathematica™, simulated in Delphi™ and animated in the 3DS Max™ graphical environment. As an applied example of RHB, we present the full spine simulator, with 150 DOF (25 movable joints each with three constrained rotations and translations), muscular excitation and contraction dynamics, spring-and-damper ligament-like dynamics, spinal-like and cerebellar-like control, and external torques and forces (including inertial, gravitational, viscous, elastic and various types of impacts).
ZMP: A REVIEW OF SOME BASIC MISUNDERSTANDINGS
Authors: VUKOBRATOVIĆ MIOMIR , BOROVAC BRANISLAV , POTKONJAK VELJKO
Published: June 2006

One of basic characteristics of the regular bipedal walk of humanoid robots is the maintenance of their dynamic balance during the walk, whereby a decisive role is played by the unpowered degrees of freedom arising at the foot–ground contact. Hence, the role of the Zero-Moment Point (ZMP) as an indicator of dynamic balance is indispensable. This paper gives a detailed discussion of some basic theoretical assumptions related to the ZMP in the light of imprecise, and even incorrect, interpretations that have recently appeared, and which have led to some erroneous conclusions. Examples are given to show some erroneous basic attitudes and the genesis of some of them is indicated. It is also pointed out that in the domain of bipedal walk there are still notions that are not clearly defined and their meanings differentiated in some related branches of science and engineering. One of the examples is dynamic balance and stability, which are often used interchangeably.
VACUUM STATE FOR SPHERICALLY SYMMETRIC SOLUTIONS OF THE COMPRESSIBLE NAVIER–STOKES EQUATIONS
Authors: XIN ZHOUPING , YUAN HONGJUN
Published: June 2006

We study the properties of vacuum states in weak solutions to the compressible Navier–Stokes system with spherical symmetry. It is shown that vacuum states cannot develop later on in time in a region far away from the center of symmetry, provided there is no vacuum state initially and two initially non-interacting vacuum regions never meet each other in the future. Furthermore, a sufficient condition on the regularity of the velocity excluding the formation of vacuum states is given.
TRANSONIC REGULAR REFLECTION FOR THE NONLINEAR WAVE SYSTEM
Authors: JEGDIĆ KATARINA , KEYFITZ BARBARA LEE , ČANIĆ SUNČICA
Published: June 2006

We consider Riemann data for the nonlinear wave system which result in a regular reflection with a subsonic state behind the reflected shock. The problem in self-similar coordinates leads to a system of mixed type and a free boundary value problem for the reflected shock and the solution in the subsonic region. We show existence of a solution in a neighborhood of the reflection point.
A DECAY THEOREM FOR SOME SYMMETRIC HYPERBOLIC SYSTEMS
Authors: MORAWETZ CATHLEEN S. , THOMASES BECCA
Published: June 2006

In this short note, we consider smooth solutions to certain hyperbolic systems of equations. We present a condition which will ensure that no shocks develop and that solutions decay in L2. The condition is restrictive in general; however, when applied to the system of one-dimensional gas dynamics it is shown that if the condition is satisfied initially then it will be satisfied for all time and therefore one obtains smooth solutions which decay.
A PRIORIBOUNDS ON SPATIAL MOTIONS OF INCOMPRESSIBLE NONLINEARLY ELASTIC RODS
Authors: ANTMAN STUART S.
Published: June 2006

The geometrically exact quasilinear evolution equations governing the spatial motion of incompressible rods and their specializations to the hyperbolic equations governing nonlinearly elastic rods have novel mathematical structures strikingly different from those for the equations governing the motion of compressible rods. The main objectives of this paper are to formulate the governing equations, an exercise requiring the solution of a sequence of semilinear hyperbolic equations of first order, and to derive a priori estimates for certain strain variables, ensuring that they cannot reach geometrically prohibited ranges in finite time. This process exhibits a new system of physically important quasilinear equations worthy of careful analysis.
HYPERBOLIC SYSTEMS OF BALANCE LAWS WITH WEAK DISSIPATION
Authors: DAFERMOS C. M.
Published: June 2006

Global BV solutions are constructed to the Cauchy problem for strictly hyperbolic systems of balance laws endowed with a rich family of entropies and source that is merely weakly dissipative, of the type induced by relaxation mechanisms.
ENTROPY STABLE APPROXIMATIONS OF NAVIER–STOKES EQUATIONS WITH NO ARTIFICIAL NUMERICAL VISCOSITY
Authors: TADMOR EITAN , ZHONG WEIGANG
Published: June 2006

We construct a new family of entropy stable difference schemes which retain the precise entropy decay of the Navier–Stokes equations, [Formula: see text] To this end we employ the entropy conservative differences of [24] to discretize Euler convective fluxes, and centered differences to discretize the dissipative fluxes of viscosity and heat conduction. The resulting difference schemes contain no artificial numerical viscosity in the sense that their entropy dissipation is dictated solely by viscous and heat fluxes. Numerical experiments provide a remarkable evidence for the different roles of viscosity and heat conduction in forming sharp monotone profiles in the immediate neighborhoods of shocks and contacts.
A DISPERSIVE APPROACH TO THE ARTIFICIAL COMPRESSIBILITY APPROXIMATIONS OF THE NAVIER–STOKES EQUATIONS IN 3D
Authors: DONATELLI DONATELLA , MARCATI PIERANGELO
Published: June 2006

In this paper we study how to approximate the Leray weak solutions of the incompressible Navier–Stokes equations. In particular we describe an hyperbolic version of the so-called artificial compressibility method investigated by J. L. Lions and Temam. By exploiting the wave equation structure of the pressure of the approximating system we achieve the convergence of the approximating sequences by means of dispersive estimates of Strichartz type. We prove that the projection of the approximating velocity fields on the divergence free vectors is relatively compact and converges to a Leray weak solution of the incompressible Navier–Stokes equation.
Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2
Authors: Subramanian Veedamali S. , Marchant Jonathan S. , Said Hamid M.
Published: June 2006

The water-soluble micronutrient thiamine is required for normal tissue growth and development in humans. Thiamine is accumulated into cells through the activity of two cell surface thiamine transporters (hTHTR1 and hTHTR2), which are differentially targeted in polarized tissues. Mutational dysfunction of hTHTR1 is associated with the clinical condition of thiamine-responsive megaloblastic anemia: the symptoms of which are alleviated by thiamine supplementation. Recently, two hTHTR2 mutants (G23V, T422A) have been discovered in clinical kindreds manifesting biotin-responsive basal ganglia disease (BBGD): the symptoms of which are alleviated by biotin administration. Why then does mutation of a specific thiamine transporter isoform precipitate a disorder correctable by exogenous biotin? To investigate the suggestion that hTHTR2 can physiologically function as a biotin transporter, we examined 1) the cell biological basis of hTHTR2 dysfunction associated with the G23V and T422A mutations and 2) the substrate specificity of hTHTR2 and these clinically relevant mutants. We show that the G23V and T422A mutants both abrogate thiamine transport activity rather than targeting of hTHTR2 to the cell surface. Furthermore, biotin accumulation was not detectable in cells overexpressing either the full length hTHTR2 or the clinically relevant hTHTR2 mutants, yet was demonstrable in the same assay using cells overexpressing the human sodium-dependent multivitamin transporter, a known biotin transporter. These results cast doubt on the most parsimonious explanation for the BBGD phenotype, namely that hTHTR2 is a physiological biotin transporter.
Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction
Authors: Arrington David D. , Van Vleet Terry R. , Schnellmann Rick G.
Published: June 2006

Calpains, Ca2+-activated cysteine proteases, are cytosolic enzymes implicated in numerous cellular functions and pathologies. We identified a mitochondrial Ca2+-inducible protease that hydrolyzed a calpain substrate (SLLVY-AMC) and was inhibited by active site-directed calpain inhibitors as calpain 10, an atypical calpain lacking domain IV. Immunoblot analysis and activity assays revealed calpain 10 in the mitochondrial outer membrane, intermembrane space, inner membrane, and matrix fractions. Mitochondrial staining was observed when COOH-terminal green fluorescent protein-tagged calpain 10 was overexpressed in NIH-3T3 cells and the mitochondrial targeting sequence was localized to the NH2-terminal 15 amino acids. Overexpression of mitochondrial calpain 10 resulted in mitochondrial swelling and autophagy that was blocked by the mitochondrial permeability transition (MPT) inhibitor cyclosporine A. With the use of isolated mitochondria, Ca2+-induced MPT was partially decreased by calpain inhibitors. More importantly, Ca2+-induced inhibition of Complex I of the electron transport chain was blocked by calpain inhibitors and two Complex I proteins were identified as targets of mitochondrial calpain 10, NDUFV2, and ND6. In conclusion, calpain 10 is the first reported mitochondrially targeted calpain and is a mediator of mitochondrial dysfunction through the cleavage of Complex I subunits and activation of MPT.
Neuregulin-dependent protein synthesis in C2C12 myotubes and rat diaphragm muscle
Authors: Hellyer Nathan J. , Mantilla Carlos B. , Park Eunice W. , Zhan Wen-Zhi , Sieck Gary C.
Published: June 2006

The nerve-derived trophic factor neuregulin (NRG) is a prime candidate molecule for modulating muscle fiber growth. NRG regulates signal transduction in skeletal muscle through activation of ErbB receptors present at the neuromuscular junction. In this study, we hypothesize that NRG increases protein synthesis in maturing muscle via a phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. NRG signal transduction and its ability to stimulate protein synthesis (measured by incorporation of [3H]phenylalanine into the protein pool) were investigated in differentiated C2C12 myotubes and rat diaphragm muscle (DIAm). In C2C12 myotubes, NRG dose dependently increased phosphorylation of ErbB3 and recruitment of the p85 subunit of PI3K. NRG also increased phosphorylation of Akt, a downstream effector of PI3K. NRG treatment increased total protein synthesis by 35% compared with untreated control myotubes. This NRG-induced increase in Akt phosphorylation and protein synthesis was completely blocked by wortmannin, an inhibitor of PI3K but was unaffected by PD-98059, an inhibitor of MEK. In DIAm obtained from 3-day-old rat pups, Akt phosphorylation increased ∼30-fold with NRG treatment (vs. untreated DIAm). NRG treatment also significantly increased protein synthesis in the DIAm by 29% after 3 h of incubation with [3H]phenylalanine (vs. untreated DIAm). Pretreatment with wortmannin abolished the NRG-induced increase in protein synthesis, suggesting a critical role for PI3K in this response. The results of the present study support the hypothesis that nerve-derived NRG contributes to the regulation of skeletal muscle mass by increasing protein synthesis via activation of PI3K.
Exercise training blunts microvascular rarefaction in the metabolic syndrome
Authors: Frisbee Jefferson C. , Samora Julie Balch , Peterson Jonathan , Bryner Randall
Published: June 2006

Reduced skeletal muscle microvessel density (MVD) in the obese Zucker rat (OZR) model of the metabolic syndrome is a function of a chronic reduction in vascular nitric oxide (NO) bioavailability. Previous studies suggest that exercise can improve NO bioavailability and reduce chronic inflammation and that low vascular NO bioavailability may be associated with impaired angiogenic responses via increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. As such, we hypothesized that chronic exercise (EX) would increase NO bioavailability in OZR and blunt microvascular rarefaction through reduced MMP activity, and potentially via altered plasma cytokine levels. Ten weeks of treadmill exercise (1 h/day, 5 days/wk, 22 m/min) reduced body mass and fasting insulin and triglyceride levels in EX-OZR vs. sedentary (SED) OZR. In EX-OZR, gastrocnemius muscle MVD was improved by 19 ± 4%, whereas skeletal muscle arteriolar dilation and conduit arterial methacholine-induced NO release were increased. In EX-OZR, functional hyperemia was improved vs. SED-OZR, and minimum vascular resistance within perfused gastrocnemius muscle was reduced, although no change in arteriolar stiffness was identified. Western blotting and gelatin zymography demonstrated that neither expression nor activity of MMP-2 or MMP-9 was altered in skeletal muscle of EX vs. SED animals. Plasma markers of inflammation associated with angiogenesis, monocyte chemoattractant protein-1 and IL-1β, were increased in SED-OZR and were reduced with training, whereas IL-13 was reduced in SED-OZR and increased with exercise. These data suggest that exercise-induced improvements in skeletal muscle MVD in OZR are associated with increased NO bioavailability and may stem from altered inflammatory profiles rather than MMP function.
Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice
Authors: Bhatia Madhav , Zhi Liang , Zhang Huili , Ng Siaw-Wei , Moore Philip K.
Published: June 2006

We have shown earlier that H2S acts as a mediator of inflammation. In this study, we have investigated the involvement of substance P and neurogenic inflammation in H2S-induced lung inflammation. Intraperitoneal administration of NaHS (1–10 mg/kg), an H2S donor, to mice caused a significant increase in circulating levels of substance P in a dose-dependent manner. H2S alone could also cause lung inflammation, as evidenced by a significant increase in lung myeloperoxidase activity and histological evidence of lung injury. The maximum effect of H2S on substance P levels and on lung inflammation was observed 1 h after NaHS administration. At this time, a significant increase in lung levels of TNF-α and IL-1β was also observed. In substance P-deficient mice, the preprotachykinin-A knockout mice, H2S did not cause any lung inflammation. Furthermore, pretreatment of mice with CP-96345 (2.5 mg/kg ip), an antagonist of the neurokinin-1 (NK1) receptor, protected mice against lung inflammation caused by H2S. However, treatment with antagonists of NK2, NK3, and CGRP receptors did not have any effect on H2S-induced lung inflammation. Depleting neuropeptide from sensory neurons by capsaicin (50 mg/kg sc) significantly reduced the lung inflammation caused by H2S. In addition, pretreatment of mice with capsazepine (15 mg/kg sc), an antagonist of the transient receptor potential vanilloid-1, protected mice against H2S-induced lung inflammation. These results demonstrate a key role of substance P and neurogenic inflammation in H2S-induced lung injury in mice.