cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of cations on cartilage structure swelling of growth plate and degradation of proteoglycans induced by chelators of divalent cations

Slices of fresh ovine and bovine epiphyseal cartilages swell following extraction in 0.05 M disodium ethylenediaminetetraacetate (EDTA) in Tris buffer, pH 5.8 and 7.4, at 4° and 37°. The swelling is strikingly visible to the unaided eye and is most pronounced in the growth plate region of the epiphysis. Other chelators—ethyleneglycolbis(β-aminoethyl ether)N,N′-tetraacetic acid (EGTA), and citrate buffer—also induce swelling. Swelling is associated with increased degradation of proteoglycans (PG) especially at pH 5.8, however, collagen seems to be unaffected. These effects are prevented by the addition of certain divalent cations (Ca, Mg, Zn) to the extraction media. At higher concentrations, the monovalent cation sodium also prevents swelling. It is concluded that divalent cations are required to maintain structure and function of cartilage. Freezing and thawing the cartilage did not prevent swelling or degradation, which suggests that these phenomena are not dependent on living chondrocytes. Although PG degradation and loss is markedly increased at 37° as compared with 4°, swelling is unaffected. It is concluded therefore that the degradative effects are enzymatic but the swelling is physicochemical. Other cartilages (nasal, manubrium) also swell and show histochemical evidence of PG degradation. These effects are minimal compared with the effects induced in the growth plate. It is inferred that growth plate contains more proteases than other cartilages and has properties that make it more susceptible to swelling. Swelling of the growth plate occurs even when the metaphysis is attached to it albeit to a lesser extent than when it is freed of underlying bone. A hypothesis is offered which attempts to link these phenomena with chondrocyte and matrical imbibition of water (swelling) in the zone of hypetrophy of the growth plate.
Long-term benthic infaunal monitoring at a deep-ocean dredged material disposal site off Northern California

Abstract One hundred and thirty-five benthic infaunal samples were collected from the San Francisco Deep-Ocean Disposal Site (SF-DODS) over a 10-year period from January 1996 to September 2004. Each sample was 0.1 m2, cut to a depth of 10 cm, and sieved through a 300-μm mesh. A total of 810 species of benthic invertebrates were identified; the majority of taxa (65.4%) new to science. The fauna represents a rich lower slope infaunal assemblage that rivals similarly studied locations in the western North Atlantic. No regional impact or degradation of benthic infauna due to dredged material disposal was detected. All reference stations and stations on the site boundary maintained high species richness and diversity during the monitoring period. Exceptions included an occasional sample with anomalously high numbers of one or two species that reduced the diversity and/or equitability. Within SF-DODS species richness and diversity were often reduced. Stations within the disposal site were recolonized by the same taxa that normally occurred in adjacent reference areas. Initial colonizers of fresh dredged material included spionid and paraonid polychaetes that were typical dominants at the site. At least one polychaete species, Ophelina sp. 1, sometimes colonized dredged materials containing coarse sand. One sample at Station 13, located in the middle of SF-DODS (September 2002), contained 57 species of benthic invertebrates, suggesting that colonization of fresh dredged material is rapid. It seems unlikely that larval dispersal and settlement account for this rapid recolonization; therefore it is postulated that adult organisms from adjacent areas move to the disturbed sites via boundary layer currents. The steep continental slope adjacent to SF-DODS is subject to turbidity flows and the resident fauna are likely pre-adapted to rapidly colonize disturbed sediments. Larval dispersal, especially by spionid polychaetes such as Prionospio delta, may also be important in colonizing newly deposited sediments. Subtle year-to-year shifts in faunal assemblages were evident at stations on the boundary of SF-DODS. At these stations species richness and diversity remained high, but numerically dominant taxa differed, possibly due to changes in sediment grain size associated with the dredged material. However, some year-to-year changes appeared to be regional in nature. Large epifaunal organisms such as the elasapoid holothurian Scotoplanes globosa appeared to be locally important in modifying surficial sediments: it moves through the sediment like a bulldozer, disturbing the surface and disrupting resident infauna as it ingests sediment. Other deposit-feeding holothurians such as Ypsilothuria bitentaculata were found throughout the study area including sediments with fresh dredged material. A long, narrow-bodied tube-like agglutinated foraminiferan of the genus Bathysiphon is commonly found in sediments containing dredged material. This foraminiferan is poorly understood, but may be opportunistic on soft dredged material.
Comment on Misra and Gergen's: Place of Culture in Psychological Science

Abstract This well written paper makes some useful and important points, but the contrasts they provide between mainstream psychology, cross-cultural psychology, and pluralistic human science are greatly exaggerated and in some respects inaccurate.
Paleogeographic and structural significance of an Upper Mississippian facies boundary in southern Nevada and east-central California: Discussion and reply

A major facies boundary separating Meramecian (lower Upper Mississippian) shallow-water, carbonate-platform rocks to the south-east from coeval to slightly younger relatively deep-water siliciclastic rocks to the northwest can be traced throughout southern Nevada and east-central California. Although the precise depositional relation between the two facies is not entirely clear, the outer margin of the shallow-water carbonate rocks almost certainly marks the edge of the carbonate platform in earliest late Meramecian time. This facies boundary is distinct and unambiguous enough that it and a parallel subfacies boundary within the carbonate-platform rocks can be used to estimate amounts of displacement on Cenozoic right-slip faults in the region. The carbonate-siliciclastic facies boundary is offset by about 170 km in a right-lateral sense parallel to the Death Valley-Furnace Creek fault zone between the west side of that fault zone and the northeast side of the Las Vegas Valley shear zone. This offset is Cenozoic in age and is interpreted to be distributed as follows: 45-50 km on the Las Vegas Valley shear zone, 80 km on the Death Valley-Furnace Creek fault zone, 30 km on the Stewart Valley fault, and an additional 10-15 km that is not specifically accounted for. Restoration of these offsets successfully reconstructs the Meramecian carbonate shelf edge and aligns several thrust faults now exposed on opposite sides of the right-slip faults.
Phorbol ester exposure activates an AP-1-mediated increase in ERCC-1 messenger RNA expression in human ovarian tumor cells.

ERCC-1 is an essential gene in the nucleotide excision repair pathway, and may be essential for life. However, the mechanism of transcriptional activation and regulation of ERCC-1 gene expression is unclear. We therefore investigated the effect of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the ERCC-1 gene in A2780/CP70 human ovarian carcinoma cells. TPA induced a four- to sixfold increase in steady-state ERCC-1 messenger RNA (mRNA) levels that was time- and concentration-dependent. Nuclear run-on experiments demonstrated that the rate of transcription of ERCC-1 was approximately 2.8-fold higher in TPA-treated cells than in the controls. TPA stimulation of A2780/CP70 cells also resulted in a rapid but transient induction of c-jun and c-fos as determined by Northern and Western blot analyses, which peaked about 2 h before the peak in ERCC-1 expression. Electrophoretic mobility shift assays of nuclear extracts from TPA-treated cells revealed an increase in DNA-binding activity specific for the AP-1-like binding site in the 5′-flanking region of ERCC-1. c-Jun and c-Fos proteins were confirmed to be the components of the activated AP-1 complex by supershift analysis. The increase in AP-1 activity occurs immediately before the increase in ERCC-1 transcription. The increase in AP-1 DNA-binding activity and the increase in ERCC-1 mRNA expression were prevented by pretreatment with cycloheximide. These data suggest that AP-1 may contribute to the upregulation of ERCC-1 in response to TPA in human ovarian cancer cells.
A model of surface site types on oxide and silicate minerals based on crystal chemistry; implications for site types and densities, multi-site adsorption, surface infrared spectroscopy, and dissolution kinetics

In this study, a method for estimating site types and ionizable site densities at mineral surfaces by consideration of ideal crystal surfaces has been developed. Periclase, rutile, goethite, hematite, corundum, kaolinite, andalusite, sillimanite, sanidine, albite, anorthite, and quartz surfaces were considered, both because they represent a wide range of crystal structures and because many adsorption and dissolution studies have focused on these minerals. For each mineral, the predominant cleavage or growth faces were studied. To avoid choosing arbitrary slices of the crystal parallel to each cleavage or growth face, the total Brown bond strengths (and the resulting partial charges on coordinatively unsaturated atoms) were calculated for the bonds that must be broken to generate each possible ideal slice on a given plane. The charge-neutral or nearly charge-neutral slices produced with a minimum total strength of bonds severed were examined with the aid of the commercial computer program Crystal-Maker C . Once the ideal mineral surface for a given plane was chosen, the number of sites per unit surface area was calculated using five different methods. For the minerals considered, calculated site densities for a given surface ranged from 0 to 40.8 sites/nm 2 , a considerably larger range than the density of 2.3 to 10 sites/nm 2 that is often cited. The results from each of the methods were compared to available experimental estimates of surface hydroxyl site densities from temperature desorption experiments, infrared data, and tritium exchange methods and to ionizable or reactive site densities from acid-base titrations and chemical reaction methods. Estimates based on the number of broken bonds gave the best agreement with site densities using the tritium exchange method. However, estimates based on the number of coordinatively unsaturated atoms or on the partial charge of coordinatively unsaturated atoms were also consistent with much of the available tritium exchange data. Predicted site types were compared with the available spectroscopic data. Implications of predicted site types with respect to the interpretation of infrared data and for improving adsorption and dissolution rate models are discussed.
Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis

Lupus nephritis is an immune-mediated disease, where antibodies and T cells both play pathogenic roles. Since spontaneous lupus nephritis in mouse models takes 6-12 months to manifest, there is an urgent need for a mouse model that can be used to delineate the pathogenic processes that lead to immune nephritis, over a quicker time frame. We propose that the experimental anti-glomerular basement membrane (GBM) disease model might be a suitable tool for uncovering some of the molecular steps underlying lupus nephritis. This article reviews the current evidence that supports the use of the experimental anti-GBM nephritis model for studying spontaneous lupus nephritis. Importantly, out of about 25 different molecules that have been specifically examined in the experimental anti-GBM model and also spontaneous lupus nephritis, all influence both diseases concordantly, suggesting that the experimental model might be a useful tool for unraveling the molecular basis of spontaneous lupus nephritis. This has important clinical implications, both from the perspective of genetic susceptibility as well as clinical therapeutics.
Mechanism of Pd(OAc)2/Pyridine Catalyst Reoxidation by O2: Influence of Labile Monodentate Ligands and Identification of a Biomimetic Mechanism for O2 Activation

The mechanism of catalyst oxidation by O(2) in Pd-catalyzed aerobic oxidation reactions has been the subject of considerable debate, particularly with respect to the reactivity of Pd(II)-hydride species. Here, we describe the use of unrestricted DFT computational methods to investigate the mechanism of catalyst reoxidation with the Pd(OAc)(2)/pyridine catalyst system, one of the most widely used catalysts. These studies probe four different pathways for the formation of a Pd(II)-hydroperoxide species from the reaction of O(2) from the corresponding Pd(II)-hydride [(py)(n)Pd(II)(H)OAc]: 1) a homolytic pathway involving hydrogen-atom abstraction by O(2); 2) AcOH reductive elimination to yield a Pd(0) species that subsequently reacts with O(2); 3) migratory insertion of O(2) into a Pd-H bond; and 4) oxidative addition of O(2) to Pd(II) to yield a Pd(IV)(eta(2)-peroxo) species. In contrast to previous studies of reactions between O(2) and Pd-hydride species, the reductive-elimination pathway (mechanism 2) is significantly more favorable than any of the other pathways. This outcome is traced to the presence of labile ligands (pyridine) that can readily dissociate from Pd to enable the hydride and acetate ligands to occupy cis-coordination sites. These results strongly support the involvement of Pd(0) as an intermediate in the catalytic cycle. Investigations of the mechanism of the reaction of O(2) with the Pd(0) intermediate revealed a novel, previously unrecognized mechanism that yields a Pd-OOH product without proceeding through the intermediacy of a Pd(II)(eta(2)-peroxo) species. This mechanism resembles pathways commonly observed in biological O(2) activation and suggests that noble-metal and biological oxidation mechanisms may be more similar than previously appreciated.
Genetic algorithm optimization of a molecular mechanics force field for technetium

Abstract A new force field was developed using genetic algorithms (GAs) to optimize molecular mechanics (MM) parameters. The GA-MM approach was applied to the study of technetium (Tc) complexes with coordination numbers of 5 or 6 and formal oxidation states of +3 to +6 on the metal. Both soft and hard donor ligands, coordinated through dative, single, and multiple bonds to Tc, were studied. The new GA-MM force field was tested for the prediction of metric parameters (bond lengths, bond angles and dihedral angles) and overall geometry in reference to X-ray crystallographic data. Despite the chemical diversity found in technetium coordination chemistry, good modeling was achieved in a fraction of the time of higher-level, quantum-based methods, with considerably less computational resources. The GA-MM approach is general enough to be applicable to other d-block metals.
β2-Adrenoceptor influences on the α1- and α2-mediated vasoconstriction induced by phenylpropanolamine and its two component enantiomers in the pithed rat

Phenylpropanolamine (PPA, (+/-)-norephedrine) is commonly found in appetite suppressants and nasal decongestants. Within the cardiovascular system of the pithed rat, the drug and its two component enantiomers ((-)- and (+)-norephedrine) are largely direct-acting agonists. The interaction between simultaneous alpha 1-, alpha 2- and beta 2-adrenoceptor mediated effects of the drug and its two enantiomers have been examined using the cardiovascular system of the pithed rat. On all adrenoceptors tested the potency was (-)- greater than (+/-)-, greater than (+)-norphedrine. The alpha 1- and alpha 2-mediated pressor responses of each were enhanced in the presence of the beta 2-adrenoceptor antagonist, ICI 118,551, and diminished in the presence of the selective beta 2-adrenoceptor agonist salbutamol. It is concluded that each form of the drug possesses the intrinsic ability to interact with the alpha 1-, alpha 2- and beta 2-adrenoceptors in the system used and that the interaction with those adrenoceptors determines the net increase in diastolic blood pressure that follows the intravenous administration of the compounds. These findings have a bearing on the recent controversy regarding the use of beta-blocking agents in the treatment of overdosage of the drug.
Improvements of Satellite SST Retrievals at Full Swath

The ultimate goal of the prediction of Sea Surface Temperature (SST) from satellite data is to attain an accuracy of 0.3°K or better when compared to floating or drifting buoys located around the globe. Current daytime SST algorithms are able to routinely achieve an accuracy of 0.5°K for satellite zenith angles up to 53°. The full scan swath of VIIRS (Visible Infrared Imaging Radiometer Suite) results in satellite zenith angles up to 70°, so that successful retrieval of SST from VIIRS at these higher angles would greatly increase global coverage. However, the accuracy of present SST algorithms steadily degrades to nearly 0.7°K as the satellite zenith angle reaches 70°, due mostly to the effects of increased atmospheric path length. We investigated the use of T field , a gap-free first guess temperature field used in NLSST, as a separate predictor to the MCSST algorithm in order to clearly evaluate its effects. Results of this new algorithm, TfieldSST, showed how its rms error is heavily dependent on the aggressiveness of the pre-filtering of buoy matchup data with respect to Tfield. It also illustrated the importance of fully exploiting the a priori satellite-only information contained in T field , presently tamed in the NLSST algorithm due to the fact that it shows up as a multiplier to another predictor. Preliminary results show that SST retrievals using TfieldSST could be obtained using the full satellite swath with a 30% improvement in accuracy at large satellite zenith angles and that a fairly aggressive pre-filtering scheme could help attain the desired accuracy of 0.3°K or better using over 75% of the buoy matchup data.
Assay of Pig Growth Hormone Preparations for Metabolic Activities in the Rat and in Man

The possible somatotropic effect in man of porcine growth hormone (pGH) and its plasmin digest has not been comprehensively studied before. For this purpose, pGH was digested with rat or human plasmin; acrylamide gel electrophoresis showed less than 10% native pGH remaining in the digests. Native pGH and the 2 types of plasmin digest possessed similar GH potency, as measured by the weight gain assay in the hypophysectomized rat: 1-2 IU/mg. In 7 GH-deficient children and 3 adults with myotonic dystrophy, we measured the capacity of human GH (hGH), pGH, and pGH plasmin digests to cause: a) the retention of N, P, K, Na, and Cl; b) a rise in plasma free fatty acids; c) a fall in plasma alpha-amino NL d) impaired glucose tolerance; and e) hyperinsulinemia. Human GH was active in all respects at minimal effective dosages of .0168 to 0.168 IU/kg BW(3/4) per day. The pGH preparations had no detectable effect at 0.532 I.U./kg BW(3/4)/day. The data show that in man pGH and its plasmin digests possess less than 1/30, less than 1/10, and less than 1/3 the anabolic, adipokinetic, and diabetogenic potencies of hGH, respectively.
Atmospheric, Evolutionary, and Spectral Models of the Brown Dwarf Gliese 229 B

Theoretical spectra and evolutionary models that span the giant planet-brown dwarf continuum have been computed based on the recent discovery of the brown dwarf Gliese 229 B. A flux enhancement in the 4- to 5-micrometer wavelength window is a universal feature from jovian planets to brown dwarfs. Model results confirm the existence of methane and water in the spectrum of Gliese 229 B and indicate that its mass is 30 to 55 jovian masses. Although these calculations focus on Gliese 229 B, they are also meant to guide future searches for extrasolar giant planets and brown dwarfs.
Seeking Food Justice

Seeking justice, as Christians, means seriously reconsidering our food consumption in light of multiple instances of injustice: maltreatment of workers, animals, and the environment; and misdistrib...
Genotypic diversity of Francisella tularensis infecting Dermacentor variabilis ticks on Martha's Vineyard, Massachusetts

Martha's Vineyard, Mass., has been the site of two outbreaks of tularemia (1978 and 2000). Although most patients from both outbreaks presented with pneumonic disease and although aerosol transmission has been suggested, the bite of a dog tick and exposure to rabbits remain the only proven modes of transmission. The factors that precipitated the tularemia outbreaks or the proximal determinants of human risk remain undescribed. We sought to test the hypothesis that the ongoing outbreak is due to a recent introduction event as opposed to amplification of a cryptic enzootic cycle. From 2001-2003, we collected 4,246 dog ticks and tested them in pools for evidence of tularemia by PCR. We then measured the genetic diversity of Francisella tularensis by using multiple-locus variable-number tandem repeat analysis. The prevalence of F. tularensis in dog ticks averaged 0.7%. From 29 positive pools, we identified 10 unique genotypes, which was an unexpectedly large degree of diversity (Simpson's index = 0.86). This degree of genetic diversity is inconsistent with a recent introduction event. We conclude that there has been long-standing enzootic transmission of tularemia on the island.
Efficient Demyristoylase Activity of SIRT2 Revealed by Kinetic and Structural Studies

Sirtuins are a class of enzymes originally identified as nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacetylases. Among the seven mammalian sirtuins, SIRT1-7, only SIRT1-3 possess efficient deacetylase activity in vitro, whereas SIRT4-7 possess very weak in vitro deacetylase activity. Several sirtuins that exhibit weak deacetylase activity have recently been shown to possess more efficient activity for the removal other acyl lysine modifications, such as succinyl lysine and palmitoyl lysine. Here, we demonstrate that even the well-known deacetylase SIRT2 possesses efficient activity for the removal of long-chain fatty acyl groups. The catalytic efficiency (kcat/Km) for the removal of a myristoyl group is slightly higher than that for the removal of an acetyl group. The crystal structure of SIRT2 in complex with a thiomyristoyl peptide reveals that SIRT2 possesses a large hydrophobic pocket that can accommodate the myristoyl group. Comparison of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 reveals that the acyl pockets of SIRT1-3 are highly similar, and to a lesser degree, similar to that of SIRT6. The efficient in vitro demyristoylase activity of SIRT2 suggests that this activity may be physiologically relevant and warrants future investigative studies.
The sensation and regulation of interactions with the extracellular environment: the cell biology of lymphocyte adhesion receptors.

CONTENTS INTRODUCTION 360 Adhesion in Developmental Biology and the Immune Response . . . . . ... . . . . . . . ... . . . . . . . . ... . . . . 360 Dissection 0/ the Molecular Basis of T Lymphocyte Recognition with Monoclonal Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . 361 THE T CELL ANTIGEN RECEPTOR AND ASSOCIATIVE RECOGNITION B Y CD4 O R CDS 364 THE ACTIVATION-REGULATED CO2: LFA-3 AND LFA-I : ICAM ADHESION MECHANISMS 366 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 Regulation 0/ Lymphocyte Adhesion by the CD2: LFA-3 Mechanism . . . . . . . . . . . . . . . . . . . . . . 367 ICAM-i and ICAM-2, Counter-Receptors/or LFA-i . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . 372 LFA-i Avidity: A Dynamic Mechanism/or Regulating Lymphocyte Adhesion and De-Adhesion. . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 THE INTEGRIN FAMILy 376 Structure and Ligand Specificity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 Regulation 0/ Ligand Binding and intracellular Signals . . . . . . . . .... . . . . . ..... . . . . . ..... . . . . . ..... 381 Cell Migration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . 383 ADHESION RECEPTOR PHENOTYPE AND LYMPHOCYTE BEHAVIOR 384 Education of Lymphocytes Stably A lters A dhesion Receptor Phenotype . . . . . . . . . . . .. . . . . . . 384 Lymphocyte Recirculation Receptors . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .. . . . . ... . . . . . . . . .. . .. . 385
Fundamental Issues in Guidance and Control of Uncertain Systems

An uncertain linear dynamical system (?) is described by a state equation whose description includes uncertain parameters. These uncertain parameters are time-varying and enter into the matrices which describe the model and the connection of the inputs to the system. Once a feedback controller has been designed for such a system, it is of interest to know whether asymptotic stability of the system can be guaranteed for all admissible parameter variations within some given bounds. When this turns out to be the case, the system (?) is said to have the guaranteed stability property. The main results of this paper are summarized as follows: Given the system matrices and bounding sets which describe an uncertain single-input system, we provide necessary and sufficient conditions under which it is possible to design a controller which results in guaranteed stability. Moreover, when the sufficient conditions mentioned above are satisfied, we show that it is possible to provide a "recipe" for construction of the desired controller. A numerical example is used to illustrate the concepts presented herein.
Calmodulinopathy: A genetic trilogy

Genetic predisposition to life-threatening cardiac arrhythmia, such as in the congenital long QT syndrome (LQTS), is an important and treatable cause of sudden cardiac death in children and young adults. Among the established monogenic cardiac arrhythmia syndromes, there is tremendous allelic and genetic heterogeneity as exemplified by the more than 1000 mutations in 15 different LQTS-associated genes. Collectively, this work has established a genetic portfolio of cardiac arrhythmia susceptibility that reveals important molecular details about the pathophysiology of sudden cardiac death. Despite these advances in elucidating the genetic causes of LQTS and other arrhythmia syndromes, there remains a measurable fraction of cases that do not have a definable molecular lesion. The recent advent of next-generation sequencing has expanded the capabilities of research and clinical genetic laboratories to identify mutations in known and previously unknown genes causative of monogenic cardiovascular disorders. Recently, application of exome sequencing in genotype-negative LQTS probands allowed discovery of mutations in 2 genes (CALM1, CALM2) encoding the ubiquitous calcium binding protein calmodulin. To date, there have been 11 reported calmodulin mutations with approximately equal numbers in CALM1 and CALM2 causing LQTS, catecholaminergic polymorphic ventricular tachycardia, or idiopathic ventricular fibrillation. Nearly all of the identified calmodulin mutations impair Ca2þ binding to the protein and disrupt its capability to modulate specific molecular targets in heart. For calmodulin mutations associated with LQTS, impaired Ca2þdependent inactivation of L-type voltage-gated Ca2þ channels was demonstrated to be a likely pathophysiologic mechanism predisposing to prolonged action potential duration and arrhythmogenicity. By contrast, calmodulin mutations associated with catecholaminergic polymorphic ventricular tachycardia interfere with normal regulation of the intracellular Ca2þ release channel, increasing the probability of spontaneous sarcoplasmic Ca2þ release and
New approaches to control foot-and-mouth disease: antivirals and novel vaccines

Summary Foot and mouth disease (FMD) is a highly contagious viral-induced disease of cloven-hoofed animals that results in serious economic consequences in affected countries that have a significant international livestock trade. Currently disease control measures include inhibition of susceptible animal movement, slaughter of infected and susceptible in-contact animals, disinfection, and possibly vaccination with an inactivated whole virus antigen. However, there are a number of problems with use of the current vaccine in outbreaks in countries which have been previously free of FMD. As a result countries which vaccinate face a longer delay in regaining FMD-free status than countries which do not vaccinate but rather slaughter all infected or susceptible in-contact animals. Researchers have been attempting to develop both new FMD vaccines to overcome the limitations of the current inactivated vaccine as well as methods to more rapidly induce a protective response. In this manuscript I discuss the most effective new FMD vaccines and novel antiviral strategies that are currently being examined.
The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count: findings from the Third National Health and Nutrition Examination Survey.

To examine the association between the metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count, the author did a cross-sectional analysis of data from 8570 participants aged >/=20 years from the Third National Health and Nutrition Examination Survey (1988-1994). The metabolic syndrome was defined using criteria established by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The age-adjusted prevalence of having an elevated C-reactive protein concentration was 29.0% (S.E.: 1.6%) for participants with the metabolic syndrome and 12.1% (S.E.: 0.6%) for participants without the metabolic syndrome (adjusted odds ratio (OR), 2.80; 95% confidence interval (CI): 2.36, 3.33). Compared with participants who had no abnormalities, the corresponding adjusted ORs were 1.91 (95% CI: 1.27, 2.87), 3.00 (95% CI: 1.96, 4.60), 5.01 (95% CI: 3.39, 7.41), 5.97 (95% CI: 3.83, 9.31), and 6.79 (95% CI: 3.55, 12.99) for participants with 1, 2, 3, 4, and 5 metabolic abnormalities, respectively. Participants with the metabolic syndrome had higher fibrinogen concentrations and white blood cell counts than those without this syndrome. Many people with the metabolic syndrome have a low-grade inflammation, which may increase their risk for future adverse events. A better understanding of the potential consequences of the high prevalence of low-grade inflammation among people with the metabolic syndrome is needed.
Harpoon-based Sampling for Planetary Applications

Harpoon-based sampling techniques for sample acquisition from planetary rovers and aerobots have been developed. The approach enables access to samples on nearby steep terrain or from unstable mobile platforms with small mass and volume impacts. For rover-based sampling, alterative harpoon concepts were compared and the crossbow approach was selected. A prototype system was fabricated, mounted on a rover, and tested in the JPL marsyard. Also, two penetrator concepts were developed and tested for aerobot deployment to icy-regolith environments. One concept is a passive drop penetrator and the other is an active pyro-activated penetrator. Results of both the design and test efforts with the harpoon-based sampling systems are presented.
Wireless multicasting via iterative optimization

A class of wireless multicast utility optimization problems are considered. Assume network utility is only a function of link throughput and nodes' transmission power. Under a set of physical layer assumptions, the impact of physical and data-link layer configurations to the upper layers in a wireless network can be characterized using a configuration graph. Network layer utility optimization can consequently be carried out via iterations that optimize network layer algorithms over the configuration graph and revise physical, data-link layer configurations to improve the configuration graph. For a class of wireless multicast networks with optimal network coding, the number of point-to-multipoint links involved in network utility optimization is only polynomial, as opposed to exponential, in the number of nodes. This leads to a reduced complexity in exhaustive searching algorithms, such as optimal utility maximization. Consequently, simulations of these algorithms for moderate-sized networks become feasible. 1
PSYCHOMACHIA IN ART FROM PRUDENTIUS TO PROUST

La vie du chretien comme combat spirituel contre des ennemis tant exterieurs qu'interieurs, trouve son expression dans la " Psychomachia " du poete Prudence. Ce poeme, ecrit vers 400, qui met en scene un combat allegorique des vices et vertus, a eu une grande influence sur la poesie et la sculpture medievales. L'A. retrouve le theme de la psychomachie chez Proust, aussi bien au sens litteral qu'allegorique, moral et anagogique
Targeting developmental pathways in children with cancer: what price success?

Summary Much of current cancer research is aimed at exploiting cancers' molecular addictions through targeted therapeutics, with notable successes documented in clinical trials. By their nature, these agents have different side-effect profiles than conventional chemotherapy drugs. Although few targeted agents have attained regulatory approval for use in children, paediatric oncologists are gaining experience with these drugs, which can have unique short-term and long-term effects in developing children that are unrecognised in adults. This Review summarises the rationale for targeted therapy, challenges in paediatric drug development, unique side-effect profiles of targeted agents, limited data from children treated with targeted agents, and implications of current knowledge and gaps therein. The demonstrated and potential effects of targeted therapies on normal tissue development and function are discussed. Future clinical trial design should include carefully considered assessment of the developmental effects of targeted therapy, and informed supportive-care recommendations.
A critical review of ultra-accelerated tests for alkali-silica reactivity

Abstract A large number of ultra-accelerated test procedures, for determining the potential alkali reactivity of aggregates, have been developed, particularly in the past 15 years. An ultra-accelerated test method is defined as one which yields results within a few days or, at most, a few weeks. A number of ultra-accelerated test methods have been adopted as ‘standard tests’, but few have been adequately evaluated. The rapid globalization of the construction industry will require the harmonization of National Standard Test Methods. The major requirement of ultra-accelerated test methods is that they should correctly predict the potential reactivity of aggregates in greater than 95% of the cases. Due to the complexity and variability in the composition and grain size of aggregates, it is improbable that a single test method will be developed which would be appropriate for evaluating all types of aggregates. Another major requirement for ultra-accelerated test methods is that the interlaboratory coefficient of variation should be low, preferably less than 12%. At present, only the NBRI accelerated mortar bar method has been subject to adequate inter-laboratory evaluation. However, a more limited inter-laboratory investigation showed that the autoclave mortar bar test also shows considerable potential, as a satisfactory ultra-accelerated test method. Further refinement of the NBRI and autoclave methods is required to improve their performance with a wide variety of aggregates.
Historical overview of vaccines

This article focuses on a few significant milestones in the history of vaccination. As the contributions of key investigators, such as Jenner, Pasteur, and Salk were slowly accepted, the developments and discoveries that followed pushed ahead the science of vaccinology. The article also recognizes the accomplishments of the World Health Organization and concludes with a short synopsis of vaccines being developed for the future.
Hydrology of Ice Caps in Volcanic Regions

Hydrology of Ice Caps in Volcanic Regions actually concerns itself with the hydrology of two ice caps in Iceland rather than the global topic the title implies. However, the unique condition in Iceland—an ice cap resting between two diverging plates of the Earth's crust—provides an excellent location to study ice-volcano and ice-geothermal interactions. An important motivation for this work, as for any of the glaciological studies in Iceland, is to understand the mechanics of glacier outburst floods (Jokulhlaups) that result from the release of large volumes of water stored at the base of the ice caps. Although outburst floods may be common to all glaciers, the magnitudes of the floods from Icelandic ice caps dwarf the historic outburst floods from other glaciers and are the largest glacier outburst floods in historic times, usually exceeding 1 km3 and occasionally exceeding 5 km3! The peak water discharge during these events can reach 40,000 m3/s, which exceeds the average flow of the Mississippi River. Considering that these floods occur every 2'10 years and cause havoc to transportation routes (the Icelanders will not live in flood plains), an understanding of how these floods develop is extremely important.
Derivation of a Reliability Metric for Fused Data Decision Making

Users require information fusion to reduce dimensionality for real world, complex decision-making. Typically, researchers design fusion systems based on limited data that does not capture all operating conditions seen in the real world (i.e. weather for video sensors). Fusion systems are of limited use when presented with poor data, inappropriate models, and unrealistic assumptions. Decision makers are burdened with the task of determining the quality of fused output based on trial and error. If the fusion system works in most scenarios, aids the user in purposeful decisions, and leady to successful actions; the user has high system confidence. However, if the fusion system causes erroneous results that lead to poor decisions, the user disposes of the entire system - which could have been the result of bad data, incomplete models, and restricted assumptions. Thus, when a fusion system is fielded, there has to be metrics associated with model fidelity, data uncertainty, and constraints over applicability. By combing representations of data quality; this paper derives a reliability metric to aid users to trust fusion outputs, perform a utility assessment, and refine sensor collections.
Sediment magnetic properties reveal Holocene climate change along the Minnesota prairie-forest ecotone

We propose a model that explains variations in magnetic parameters of lake sediments as a record of Holocene climate change. Our model is based on records from four lakes and incorporates the effects of erosion, dust deposition, and the authigenesis and diagenesis of the magnetic component of the sediment. Once checked against high resolution multi proxy climate records, which are currently being established for some of our study sites, it will allow us to use magnetic proxies to establish high-resolution climate reconstructions on a regional scale. Our model utilizes a combination of concentration-dependent parameters (magnetic susceptibility, IRM) and grainsize-dependent parameters (ARM/IRM, hysteresis parameters). Magnetic mineralogy is characterized by a combination of low-temperature measurements and S-ratios, and our magnetic measurements are complemented by XRD, LOI and smearslide analyses. During periods of forest growth within the watershed, deposition of terrigenous material is low and the sediment magnetic properties are characterized by low concentrations of mainly authigenic minerals (low values of IRM, high ratios of ARM/IRM). During the early to mid-Holocene dry period, deposition of terrigenous material increased due to intensified dust deposition and the erosion of lake margins caused by lowered water levels. Concentration of magnetic minerals increases (high IRM, χ) and so does the grain-size of the magnetic fraction (low ARM/IRM). During the late Holocene, sediment magnetic properties depend on the varied position of the site with respect to the prairie–forest ecotone.
A town meeting: SIGCSE committee on expanding the women-in-computing community (abstract only)

In January 2004, we organized the second SIGCSE Committee ("Expanding the Women-in-Computing Community"). Our annual Town Meeting provides dissemination of information concerning successful gender issues projects, along with group discussion and brainstorming, in order to create committee goals for the coming year. We select projects to highlight through listserv communication and through our connections with NCWIT, ABI, ACM-W, CRA-W, etc. This year we will highlight ACM-W Chapters and ACM-W Celebrations of Women in Computing.
Morph Matters: Aggression Bias in a Polymorphic Sparrow

In species with discrete morphs exhibiting alternative behavioral strategies, individuals may vary their aggressive behavior in competitive encounters according to the phenotype of their opponent. Such aggression bias has been documented in multiple polymorphic species evolving under negative frequency-dependent selection, but it has not been well-studied under other selection regimes. We investigated this phenomenon in white-throated sparrows (Zonotrichia albicollis), a passerine with plumage polychromatism maintained by disassortative mating. The two distinct color morphs differ with respect to reproductive strategy in that white-striped birds invest more in territorial aggression than tan-striped birds. Whether territorial aggression in this species is biased according to the morph of an intruder is less understood. We found that during peak territorial and mating activity, both color morphs and sexes can exhibit aggression bias, but whether they do so depends on the strategy (morph) of the intruder. During simulated territorial intrusions, resident white-striped males and tan-striped females, which represent the opposite ends of a continuum from high to low territorial aggression, altered their territorial responses according to intruder morph. Tan-striped males and white-striped females, which represent the middle of the continuum, did not show a bias. We propose that because of the disassortative mating system and morph differences in reproductive strategy, the fitness risks of intrusions vary according to the morphs of the resident and the intruder, and that aggression bias is an attuned response to varying threats to fitness.
Carbapenem-resistant Enterobacteriaceae: a menace to our most vulnerable patients.

The past 10 years have brought a formidable challenge to the clinical arena, as carbapenems, until now the most reliable antibiotics against Klebsiella species, Escherichia coli, and other Enterobacteriaceae, are becoming increasingly ineffective. Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) pose a serious threat to hospitalized patients. Moreover, CRE often demonstrate resistance to many other classes of antibiotics, thus limiting our therapeutic options. Furthermore, few new antibiotics are in line to replace carbapenems. This public health crisis demands redefined and refocused efforts in the diagnosis, treatment, and control of infections in hospitalized patients. Here, we present an overview of CRE and discuss avenues to escape a new era of untreatable infections.
And the geophysicist replied: “Which model do you want?”

ABSTRACTMarine controlled-source electromagnetic (CSEM) and magnetotelluric (MT) soundings were carried out between 1997 and 2003 over the Gemini prospect in the Gulf of Mexico during early development of marine instrumentation. The resulting data sets provide a good test bed for examining the effect of the data type and misfit choice on regularized inversion solutions. We inverted the data sets individually and jointly for isotropic and anisotropic resistivity at a variety of data misfits. We found that multifrequency CSEM inversions vastly improved structural resolution over single-frequency inversions, suggesting that variation in skin depth added significant information. Joint MT and CSEM inversion appeared to improve resolution over MT-only inversions at depths considerably deeper than the CSEM data can resolve, probably by constraining shallow structure in the parts of the model to which the MT data were sensitive. The addition of model anisotropy improved data fit, but introduced an arbitrary scali...
Block differential encoding for rapidly fading channels

We derive a novel block differential codec to bypass estimation of rapidly fading channels. Based on a basis expansion model for time-varying channels, our differential design is easy to implement, and achieves the maximum possible Doppler diversity. Combined with a group partitioning scheme, the differential scheme provides also flexibility to tradeoff decoding complexity with performance. Simulation results corroborate our theoretical analysis.
Mars Exploration Rover Operations with the Science Activity Planner

The Science Activity Planner (SAP) is the primary science operations tool for the Mars Exploration Rover mission and NASA’s Software of the Year for 2004. SAP utilizes a variety of visualization and planning capabilities to enable the mission operations team to direct the activities of the Spirit and Opportunity rovers. This paper outlines some of the challenging requirements that drove the design of SAP and discusses lessons learned from the development and use of SAP in mission operations.
Molecular replacement by evolutionary search

Stochastic search algorithms can be used to perform rapid six-dimensional molecular-replacement searches. A molecular-replacement procedure has been developed that uses an evolutionary algorithm to simultaneously optimize the orientation and position of a search model in a unit cell. Here, the performance of this algorithm and its dependence on search model quality and choice of target function are examined. Although the evolutionary search procedure is capable of finding solutions with search models that represent only a small fraction of the total scattering matter of the target molecule, the efficiency of the search procedure is highly dependent on the quality of the search model. Polyalanine models frequently provide better search efficiency than all-atom models, even in cases where the side-chain positions are known with high accuracy. Although the success of the search procedure is not highly dependent on the statistic used as the target function, the correlation coefficient between observed and calculated structure-factor amplitudes generally results in better search efficiency than does the R factor. An alternative stochastic search procedure, simulated annealing, provides similar overall performance to evolutionary search. Methods of extending the evolutionary search algorithm to include internal optimization, selection and construction of the search model are now beginning to be investigated.