cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 75: Electron transport chain-dependent oxygen consumption in metastatic breast cancer cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Although mitochondrial ATP-production deficiency has been historically implicated to account for the Warburg effect or “aerobic” glycolysis in cancer cells, recent observations indicate the presence of functionally competent mitochondria in cancer cells. We hypothesized that a lung-metastatic breast cancer cell line with intact mitochondrial membrane potential would exhibit mitochondria-dependent oxygen consumption. A murine breast cancer cell line (4T1) was used to evaluate mitochondrial membrane potential by JC-1 fluorescence microscopy. Oxygen consumption by cancer cells in suspension was determined using a dissolved oxygen meter. Fluorescence microscopy of JC-1 red aggregates indicated the presence of highly polarized mitochondria in 4T1 cells, suggesting that these cells are capable of oxidative phosphorylation. Oxygen consumption rate of 4T1 cells suspended in 10 mM glucose-containing medium equilibrated with 21% oxygen (258 µM dissolved oxygen) at 25°C was 2.98 nmol/min/million cells (Control). Oxygen consumption was significantly enhanced by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), a mitochondrial uncoupler (7.88 nmol/min/million cells, p<0.05 vs. Control). Myxothiazol (a respiratory chain complex III inhibitor) inhibited the oxygen consumption (0.75 nmol/min/million cells; p<0.05 vs. Control), indicating the presence of a functional electron transport chain. A nitric oxide donor also inhibited oxygen consumption (0.84 nmol/min/million cells; p<0.05 vs. Control). These data indicate the presence of oxidative phosphorylation-competent mitochondria in breast cancer cells. We conclude that cancer cells possess respiration-capable mitochondria and their “aerobic” glycolysis may not reflect a compensatory mechanism for ATP generation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 75.
β-Adrenergic Stimulation Modulates Ryanodine Receptor Ca2+ Release During Diastolic Depolarization to Accelerate Pacemaker Activity in Rabbit Sinoatrial Nodal Cells

It has long been recognized that activation of sympathetic beta-adrenoceptors (beta-ARs) increases the spontaneous beating rate of sinoatrial nodal cells (SANCs); however, the specific links between stimulation of beta-ARs and the resultant increase in firing rate remain an enigma. In the present study, we show that the positive chronotropic effect of beta-AR stimulation is critically dependent on localized subsarcolemmal ryanodine receptor (RyR) Ca(2+) releases during diastolic depolarization (CRDD). Specifically, isoproterenol (ISO; 0.1 micromol/L) induces a 3-fold increase in the number of CRDDs per cycle; a shift to higher CRDD amplitudes (from 2.00+/-0.04 to 2.17+/-0.03 F/F(0); P<0.05 [F and F(0) refer to peak and minimal fluorescence]); and an increase in spatial width (from 3.80+/-0.44 to 5.45+/-0.47 microm; P<0.05). The net effect results in an augmentation of the amplitude of the local preaction potential subsarcolemmal Ca(2+) transient that, in turn, accelerates the diastolic depolarization rate, leading to an increase in SANC firing rate. When RyRs are disabled by ryanodine, beta-AR stimulation fails to amplify subsarcolemmal Ca(2+) releases, fails to augment the diastolic depolarization rate, and fails to increase the SANC firing rate, despite preserved beta-AR stimulation-induced augmentation of L-type Ca(2+) current amplitude. Thus, the RyR Ca(2+) release acts as a switchboard to link beta-AR stimulation to an increase in SANC firing rate: recruitment of additional localized CRDDs and partial synchronization of their occurrence by beta-AR stimulation lead to an increase in the heart rate.
Clinical experience with a new pulsatile assist device (PAD) during open-heart surgery.

Until now, it has not been possible to routinely use counterpulsation during open-heart surgery. A new pulsatile assist device (PAD®) has been developed to convert roller pump flow to pulsatile flow in a simple fashion. In addition, the PADr can be used as an arterial counterpulsator before and after cardiopulmonary bypass (CPB). The PAD® is inserted in the arterial line close to the aortic root. The device consists of a flexible, valveless balloon through which the arterial blood flows. The balloon is contained within a rigid plastic housing which is connected to a standard intra-aortic balloon pump unit, thereby enabling the blood-filled balloon to be squeezed. The PAD® was employed in 400 adult patients undergoing open-heart surgery for coronary artery and/or valvular heart disease from 1975 to 1978. Seventy-two percent of these patients were categorized in the New York Heart Association (NYHA) Class III or IV, or had ejection fractions of less than 0.3. The device functioned as a hemodynamically effective counterpulsator before and after CPB. Urinary outputs during CPB were more than doubled on the PAD® when compared to a control group. In addition, during CPB, coronary graft blood flow increased an average of 21.4% with the PAD®. Free plasma hemoglobin levels after CPB were not elevated. Only eight patients (2%) had a perioperative myocardial infarction. Six patients were treated with intra-aortic balloon pumping (IABP) and five survived. Total mortality in this series was eight patients (2%). It is suggested that the PAD® is a simple and reliable device for both intraoperative counterpulsation and creation of pulsatile CPB. More significantly, use of the PAD® may decrease both the incidence of perioperative myocardial infarction and the need for postoperative IABP.
On embedding rectangular meshes into rectangular meshes of smaller aspect ratio

Abstract Let G = h × w be a rectangular grid and H = s × s be the optimal square grid for G , i.e., the least square grid which is no less than G in size. Let G ′ be the grid h ′ × w ′ such that s ⩽ w ′ w and h ′ is the smallest integer such that hw ⩽ h′w′ . In this paper, a (one-to-one) embedding scheme is presented for embedding G into G ′ such that the dilation cost is at most 6. Previous results for this problem include a recent dilation 2 result for large compression ratios, and a dilation 3 result (through folding followed by compression) if the intermediate grid is not larger than the final host. To the best of our knowledge, this is the first result that allows to embed in the smallest square, regardless of the aspect ratio of the rectangle, while keeping the dilation constant . Our result is achieved using the compress and fold method, with a new compression method.
Determination of Hopfield associative memory characteristics using a simple parameter

Abstract A new statistical method is proposed for exploring the characteristics of the Hopfield associative memory (HAM). The existence of an average signal-to-noise ratio parameter (which we call C) has been successfully applied to derive equations that are capable of concisely estimating the storage capacity of (a) direct convergence nets in which the initial vector is required to precisely converge to the memorized vector in one iteration and (b) indirect convergence nets in which a specified error ϵ is allowed after multiple iterations. The close tie between the memory capacity and the required convergence probability of the HAM is described. The significance of the 1-to-1 relationship between the indirect convergence probability and the parameter ϵ/η (η = probability of a neuron state being an incorrect bit) is shown. The importance of the parameter ηN in determining the capacity of the direct convergence nets is also discussed. The theory not only provides the memory capacity for various versions of the HAM, but it gives an explicit solution for the radius of attraction parameter.
Stereoselective total syntheses of the racemic form and the natural enantiomer of the marine alkaloid lepadiformine via a novel N-acyliminium ion/allylsilane spirocyclization strategy

Stereoselective total syntheses of the racemic form and the natural enantiomer of the tricyclic marine alkaloid lepadiformine (6) have been accomplished using a novel intramolecular spirocyclization of an N-acyliminium ion with an allylsilane to form the A/C rings as the key step. Introduction of the hydroxymethyl group at C-13 of the racemic spirocycle 11 was achieved using our methodology for oxidative radical-based remote functionalization of o-aminobenzamides, followed by copper-catalyzed addition of Grignard reagent 16 to the N-acyliminium ion intermediate derived from 15. Subsequent Tamao oxidation of silane 17 then afforded the requisite hydroxymethyl compound 19, which was converted to the dimethyl acetal 25 via hydroformylation followed by aldehyde protection. Hydrolysis of the benzamide moiety of 25 and subsequent protection of the primary alcohol gave amino acetal 27. The synthesis was concluded from 27 by a four-step procedure: acid-catalyzed ring closure, amino nitrile formation, introductio...
Observer design for a steam reformer based solid oxide fuel cell system with anode recirculation

In this paper we design an observer for online estimation of species concentrations in a steam reformer based Solid Oxide Fuel Cell (SOFC) system with anode recirculation and with methane as fuel. Since in SOFCs steam reforming occurs both in the reformer and in the fuel cell, a large number of concentration sensors are necessary for accurate control of critical performance variables such as utilization and steam-to-carbon-ratio. The purpose of the observer is to reduce the number of sensors required for control. In contrast to existing observers which are either designed for chemical reactors or for fuel cells exclusively, our design considers the coupled dynamics of the reformer and the fuel cell. We design an adaptive observer where the rates of reforming reactions are treated as slowly varying unknown parameters. Using a few concentration sensors we show that all other species concentrations, molar flow rates, and reaction rates in the fuel path can be dynamically estimated. Simulation results are provided in support of the proposed design.Copyright © 2007 by ASME
Sample selection and information-theoretic alternatives to GMM

Information-theoretic alternatives to general method of moments (GMM) use over-identifying moments to estimate the data-generating distribution jointly with the parameters of interest. This paper demonstrates how these estimates can be interpreted when the sample is not a random draw from the population of interest. I make explicit the selection probability implied by the empirical likelihood and exponential tilting estimators, two commonly used estimators in this class. In addition, I propose an alternative estimator that corresponds to a logisitic selection model. The small sample properties of the estimators are demonstrated with a Monte Carlo experiment.
A history of modern treatment of aortic aneurysms.

The history of the modern treatment of aortic aneurysms is briefly reviewed, especially with reference to developments of particular interest because of improvements they brought about, controversies they initiated, and new directions they indicated as worth following. Lesions treated with considerable risk not long ago or considered operatively unmanageable are being operated upon with progressively greater safety and better results. To be sure, there are certain matters concerning which divergent opinions are held, and these debatable issues can only be resolved with further experiences. The progress which has been made foretells continued improvement in the future.
Subtypes of Asthma Defined by Epithelial Cell Expression of Messenger RNA and MicroRNA

Human asthma can be subcategorized in several ways, but one powerful approach is to subtype asthma on the basis of underlying cellular and molecular mechanisms. Groups of patients with a disease that share a common underlying biology are termed an “endotype.” Endotypes of asthma have been studied at both the cellular level (by cytological examination of induced sputum) and, increasingly, at the molecular level. Genome-wide analyses of mRNA expression within the lung have been useful in the identification of molecular endotypes of asthma and point to protein biomarkers of those endotypes that can be measured in the blood. More recently, studies of microRNA expression in airway epithelial cells in asthma have identified additional candidate biomarkers of asthma endotypes. One potentially valuable property of microRNAs is that they can also be measured in extracellular fluids and therefore have the potential to serve directly as noninvasively measured biomarkers.
The “repertoire”; of information sources

“Information source”; studies presumed that media exposure led to different attitudes and behaviors. Recent research suggests that motivations and interests lead to the selection of a set of information sources. Using ten topics this study focused on the relation of the interest people had in these topics and the sources they selected for information about the topics. As interest in a topic increased so did the number of sources, and as interest changed so did the information “repertoire.”
Add-drop filters based on mode conversion Bragg grating cavities

A new type of a resonator defined by two or more mode-converting gratings in a waveguide is proposed and analyzed. It is shown that the proposed structure can exhibit narrow resonances similar to Fabry-Perot cavities but has an advantage of being a four-port device and thus is capable of serving as an add-drop filter in various integrated optical circuits.
Models of Policy Discourse: insights versus Prediction

Policy researchers traditionally have adhered to the quantitative: (or positivist) approach. Recently, some policy analysts have emphasized a more qualitative (or postpositivist) approach. Little, if any, of the latter has been considered by proponents of the former as serious policy (i.e., “objective”) analysis. This tension has produced some conflicts as to which camp is more attuned to a policy version of “truth.” This essay attempts to demonstrate the strong and weak points of both paradigms, and argues that either by itself has serious debilitations. For instance, positivists deny the subjective nature of values that denigrate the putatively “objective” orientations of their analyses, perhaps even rendering it “undemocratic.” On the other hand, postpositivists have a difficult time operationalizing their preferred research methodologies with the necessary rigor. The essay concludes that the research problem—rather than a favorite methodology—should determine the research approach, and that both the quantitative and qualitative aspects can be used in a consonant manner.
The proconvulsant effect of nigral infusions of THIP on flurothyl-induced seizures in rat pups.

Abstract The substantia nigra γ-aminobutyric acid (GABA) system is crucial for seizure control. Our previous work indicates that in 16-day-old rat pups, nigral administration of the GABA A receptor agonist muscimol facilities flurothyl-induced seizures, whereas it suppresses seizures in adult rats. To determine whether the proconvulsant effect of muscimol in rat pups may be mediated by nigral GABA A receptors, in the present study we applied a selective GABA A receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Bilateral nigral infusions of THIP (500 or 700 ng) significantly decreased the thresholds for flurothyl seizures in a dose-dependent fashion. Doses of 350 ng or less did not significantly modify the susceptibility to seizures. An anticonvulsant action of THIP could not be detected at any dose. Administration of an effective THIP dose (500 ng) 2 mm dorsal to the SNR had no influence on seizures. These findings suggest that in rat pups the proconvulsant effect of nigral GABA A receptor agonists may be attributed to unique pharmacologic characteristics of GABA A receptors during development.
γ-sets and other singular sets of real numbers

Abstract A family of J of open subsets of the real line is called an ω-cover of a set X iff every finite subset of X is contained in an element of J . A set of reals X is a γ-set iff for every ω-cover J of X there exists 〈D n : n J ω such that X⊆ ∪ n ∩ m > n D m . In this paper we show that assuming Martin's axiom there is a γ-set X of cardinality the continuum.
The Case of Felicia: A Young Child's Strategies for Reducing Memory Demands During Mental Addition

A semi-structured clinical interview technique was used in an intensive case study of a preschool child's addition ability. The interviews uncovered a novel mental addition strategy: counting-all starting with the larger addend. This strategy minimizes the cognitively demanding double count required by mental addition strategies. Moreover, another invented strategy, a counting-like variation, was employed with problems involving a double-digit, addend to reduce mental effort.
Ordinary and Strong Ellipticity in the Equilibrium Theory of Incompressible Hyperelastic Solids

In this paper explicit necessary and sufficient conditions are established for the ordinary and strong ellipticity of the three-dimensional field equations in the nonlinear equilibrium theory of incompressible, homogeneous and isotropic, hyperelastic solids. The resulting system of inequalities involves the local principal stretches directly and in addition restricts the first and second partial derivatives of the strain-energy density with respect to the deformation invariants or the principal stretches. The conditions of ordinary and strong ellipticity are found to coalesce for materials that obey the Baker-Ericksen inequalities and possess a positive shear modulus at infinitesimal deformations. Various implications of these ellipticity conditions for special classes of materials and deformations are explored.
Structural basis for the sequence-dependent effects of platinum–DNA adducts

The differences in efficacy and molecular mechanisms of platinum based anti-cancer drugs cisplatin (CP) and oxaliplatin (OX) have been hypothesized to be in part due to the differential binding affinity of cellular and damage recognition proteins to CP and OX adducts formed on adjacent guanines in genomic DNA. HMGB1a in particular exhibits higher binding affinity to CP-GG adducts, and the extent of discrimination between CP- and OX-GG adducts is dependent on the bases flanking the adducts. However, the structural basis for this differential binding is not known. Here, we show that the conformational dynamics of CP- and OX-GG adducts are distinct and depend on the sequence context of the adduct. Molecular dynamics simulations of the Pt-GG adducts in the TGGA sequence context revealed that even though the major conformations of CP- and OX-GG adducts were similar, the minor conformations were distinct. Using the pattern of hydrogen bond formation between the Pt–ammines and the adjacent DNA bases, we identified the major and minor conformations sampled by Pt–DNA. We found that the minor conformations sampled exclusively by the CP-GG adduct exhibit structural properties that favor binding by HMGB1a, which may explain its higher binding affinity to CP-GG adducts, while these conformations are not sampled by OX-GG adducts because of the constraints imposed by its cyclohexane ring, which may explain the negligible binding affinity of HMGB1a for OX-GG adducts in the TGGA sequence context. Based on these results, we postulate that the constraints imposed by the cyclohexane ring of OX affect the DNA conformations explored by OX-GG adduct compared to those of CP-GG adduct, which may influence the binding affinities of HMG-domain proteins for Pt-GG adducts, and that these conformations are further influenced by the DNA sequence context of the Pt-GG adduct.
9.4.3 Defining System Changeability: Reconciling Flexibility, Adaptability, Scalability, and Robustness for Maintaining System Lifecycle Value

Designing and maintaining systems in a dynamic contemporary environment requires a rethinking of how systems provide value to stakeholders over time. Classically, two different approaches to promoting value sustainment may include developing either alterable or robust systems. The first accomplishes value delivery through altering the system to meet new needs, while the second accomplishes value delivery through maintaining a system to meet needs in spite of changes. The definitions of flexibility, adaptability, scalability, and robustness are shown to be different parts of the core concept of “changeability,” which can be described by three aspects: change agents, change effects, and change mechanisms. Cast in terms of system parameter changes, flexibility and adaptability are shown to relate to the origin of the change agent (external or internal to a system boundary respectively). Scalability and robustness, along with the additional property of modifiability, are shown to relate to change effects. The extent of changeability is determined by the number of possible change mechanisms available to the system as accepted by decision makers. Creating changeable systems, which can incorporate both classical notions of alterability and robustness, empowers systems to maintain value delivery over their lifecycle, in spite of changes in their contexts, thereby achieving value robustness to stakeholders over time.
Smooth muscle heavy meromyosin phosphorylated on one of its two heads supports force and motion.

Smooth muscle myosin is activated by regulatory light chain (RLC) phosphorylation. In the unphosphorylated state the activity of both heads is suppressed due to an asymmetric, intramolecular interaction between the heads. The properties of myosin with only one of its two RLCs phosphorylated, a state likely to be present both during the activation and the relaxation phase of smooth muscle, is less certain despite much investigation. Here we further characterize the mechanical properties of an expressed heavy meromyosin (HMM) construct with only one of its RLCs phosphorylated (HMM-1P). This construct was previously shown to have more than 50% of the ATPase activity of fully phosphorylated myosin (HMM-2P) and to move actin at the same speed in a motility assay as HMM-2P (Rovner, A. S., Fagnant, P. M., and Trybus, K. M. (2006) Biochemistry 45, 5280–5289). Here we show that the unitary step size and attachment time to actin of HMM-1P is indistinguishable from that of HMM-2P. Force-velocity measurements on small ensembles show that HMM-1P can generate approximately half the force of HMM-2P, which may relate to the observed duty ratio of HMM-1P being approximately half that of HMM-2P. Therefore, single-phosphorylated smooth muscle HMM molecules are active species, and the head associated with the unphosphorylated RLC is mechanically competent, allowing it to make a substantial contribution to both motion and force generation during smooth muscle contraction.
Wigner simulation of the transition of a 'single' to 'double' barrier DMS device

The presence of dilute magnetic semiconductors (DMS) enriches the design potential of nano scale barrier devices. Placement of these DMS layers within or adjacent to a barrier can effectively lower or raise the barrier height for carriers of different spin and thereby introduce separate but coupled components of current. The magnetic field in high g-factor devices then can function as a pseudo third terminal. In anticipation of an n-type technology with these materials we examine the development of a barrier device that contains a DMS layer strategically placed so that in the presence of a magnetic field the barrier device is transformed into a double barrier device. The goal of this design is to create a device that will show tunneling resonances. Some early calculations with this structure will be presented showing the possibilities, pitfalls and potential for designing such a structure.
Inhibition of 2-arachidonoylglycerol catabolism modulates vasoconstriction of rat middle cerebral artery by the thromboxane mimetic, U-46619

Background and purpose: Cerebrovascular smooth muscle cells express the CB1 cannabinoid receptor and CB1 agonists produce vasodilatation of the middle cerebral artery (MCA). The thromboxane A2 mimetic, U-46619, increased the content of the endocannabinoid, 2-arachidonoylglycerol (2-AG) in the MCA and 2-AG moderated the vasoconstriction produced by U46619 in this tissue. The purposes of this study were to examine the extent to which 2-AG is catabolized by cerebral arteries and to determine whether blockade of 2-AG inactivation potentiates its feedback inhibition of U-44619-mediated vasoconstriction. Experimental approach: The diameters of isolated, perfused MCA from male rats were measured using videomicroscopy. Key results: Exogenous 2-AG produces a CB1 receptor-dependent and concentration-related increase in the diameter of MCA constricted with 5-HT. The Emax for 2-AG dilation is increased 4-fold in the presence of the metabolic inhibitors 3-(decylthio)1,1,1-trifluropropan-2-one (DETFP), URB754 and URB597. To examine the role of catabolism in the effects of endogenous 2AG, vasoconstriction induced by U-46619 was studied. DETFP and URB754, but not the fatty acid amide hydrolase inhibitor, URB597, significantly increased the EC50 for U-46619. These data support a physiological role for endocannabinoid feedback inhibition in the effects of U-46619 and indicate that endogenously produced 2-AG is also efficiently catabolized within the MCA. Conclusions and implications: MCA express mechanisms for the efficient inactivation of 2-AG, providing further support for an endocannabinoid feedback mechanism that opposes thromboxane-mediated vasoconstriction. These data suggest that potentiation of endogenously produced 2-AG could be a novel therapeutic approach to the treatment of thrombotic stroke. British Journal of Pharmacology (2007) 152, 691–698; doi:10.1038/sj.bjp.0707468; published online 24 September 2007
The Active Approach of Stochastic Optimization with New Applications

The use of active approach in characterizing robust solutions in a linear stochastic production system is analyzed here through minimax and other solutions. Some policy implications are also discussed.
Role of Cumulus Congestus in Tropical Cyclone Formation in a High-Resolution Numerical Model Simulation

AbstractThe role of cumulus congestus (shallow and congestus convection) in tropical cyclone (TC) formation is examined in a high-resolution simulation of Tropical Cyclone Fay (2008). It is found that cumulus congestus plays a dominant role in moistening the lower to middle troposphere and spinning up the near-surface circulation prior to genesis, while deep convection plays a key role in moistening the upper troposphere and intensifying the cyclonic circulation over a deep layer. The transition from the tropical wave stage to the TC stage is marked by a substantial increase in net condensation and potential vorticity generation by deep convection in the inner wave pouch region.This study suggests that TC formation can be regarded as a two-stage process. The first stage is a gradual process of moisture preconditioning and low-level spinup, in which cumulus congestus plays a dominant role. The second stage commences with the rapid development of deep convection in the inner pouch region after the air colum...
Rate of Percutaneous Coronary Intervention for the Management of Acute Coronary Syndromes and Stable Coronary Artery Disease in the United States (2007 to 2011)

Although the benefit of percutaneous coronary interventions (PCIs) for patients presenting with acute coronary syndromes (ACS) has been established in numerous studies, the role of PCI in stable coronary artery disease (CAD) remains controversial. With the publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluations trial and the appropriate use criteria for coronary artery revascularization, we sought to examine the impact of these treatment strategies and guidelines on the current practice of PCI in United States. We conducted a serial cross-sectional study with time trends of patients undergoing PCI for ACS and stable CAD from 2007 to 2011. The annual rate of all PCI decreased by 27.7% from 10,785 procedures per million adults per year in 2007 to 2008 to 7,801 procedures per million adults per year in 2010 to 2011 (p = 0.03). Although there was no statistically significant decrease in the PCI utilization for ACS from 2007 to 2011, PCI utilization for stable CAD decreased by 51.7% (from 2,056 procedures per million adults per year in 2008 to 992 procedures per million adults per year in 2011, p = 0.02). Hospitals with a higher volume of PCI experienced a more significant decrease. Decrease in PCI utilization for stable CAD was statistically significant for patients with Medicare and private insurance/health maintenance organization (44.5%, p = 0.03 and 59.5%, p = 0.007, respectively). In conclusion, the rate of PCI decreased substantially starting from 2009 in the United States. Most of the decrease was attributed to the reduction in PCI utilization for stable CAD.
A Metric of Influential Spreading during Contagion Dynamics through the Air Transportation Network

The spread of infectious diseases at the global scale is mediated by long-range human travel. Our ability to predict the impact of an outbreak on human health requires understanding the spatiotemporal signature of early-time spreading from a specific location. Here, we show that network topology, geography, traffic structure and individual mobility patterns are all essential for accurate predictions of disease spreading. Specifically, we study contagion dynamics through the air transportation network by means of a stochastic agent-tracking model that accounts for the spatial distribution of airports, detailed air traffic and the correlated nature of mobility patterns and waiting-time distributions of individual agents. From the simulation results and the empirical air-travel data, we formulate a metric of influential spreading––the geographic spreading centrality––which accounts for spatial organization and the hierarchical structure of the network traffic, and provides an accurate measure of the early-time spreading power of individual nodes.
HPV testing as a screen for cervical cancer

Human papillomavirus (HPV) has been identified as a necessary factor in the development of pre-invasive and invasive cancers of the lower genital tract, of which cervical cancer is the most prevalent. A molecular understanding of malignant transformation and epidemiologic information has led to the development of many strategies for detection and early intervention. Newer tests for oncogenic subtypes of HPV have made it possible to predict the risk of future development of cervical cancer. This review summarizes the current understanding of HPV related disease and examines the role of HPV testing as a screening tool for cervical cancer. It summarizes the data from prospective and randomized controlled trials on HPV screening from Europe and North America and includes smaller studies from low and middle income countries where cervical cancer is the most common cancer in women.
System-level characterization of bias noise effects on electrostatic RF MEMS tunable filters

This paper presents the first system-level characterization of the effects of bias noise on the performance of high-Q electrostatic RF MEMS tunable filters. By looking at the system-level performance of such a tunable filter, this paper shows that bias noise, if not well controlled, can degrade the RF performance of the tunable filter. Quantified by error vector magnitude measurement, such system level degradation due to bias noise is found to be dependent on the frequency and amplitude of the noise signals.
The product of the pleiotropic Escherichia coli gene csrA modulates glycogen biosynthesis via effects on mRNA stability.

The carbon storage regulator gene, csrA, modulates the expression of genes in the glycogen biosynthesis and gluconeogenesis pathways in Escherichia coli and has been cloned, mapped and sequenced (T. Romeo, M. Gong, M.Y. Liu, and A.M. Brun-Zinkernagel, J. Bacteriol. 175:4744-4755, 1993; T. Romeo and M. Gong, J. Bacteriol. 175:5740-5741, 1993). We have now conducted experiments that begin to elucidate a unique mechanism for csrA-mediated regulation. Steady-state levels of glgC transcripts, encoding ADP-glucose pyrophosphorylase, were elevated by up to sixfold in a csrA::kanR mutant and were less than 6.5% of wild-type levels in a strain containing pCSR10 (csrA+), as shown by S1 nuclease protection analysis. The rate of chemical decay of these transcripts after adding rifampin to cultures was dramatically reduced by the csrA::kanR mutation. Deletion studies of a glgC'-'lacZ translational fusion demonstrated that the region surrounding the initiation codon was important for csrA-mediated regulation and indicated that neither csrA-mediated regulation nor stationary phase induction of glgC expression originates at the level of transcript initiation. Cell-free (S-200) extracts containing the CsrA gene product potently and specifically inhibited the in vitro transcription-translation of glg genes. The deduced amino acid sequence of CsrA was found to contain the KH motif, which characterizes a subset of diverse RNA-binding proteins. The results indicate that CsrA accelerates net 5'-to-3' degradation of glg transcripts, potentially through selective RNA binding.
CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is an aggressive PDGFB-dependent cutaneous sarcoma characterized by infiltrative growth and frequent local recurrences. Some DFSP progress to a higher-grade fibrosarcomatous form, with rapid growth and increased risk of metastasis. Imatinib provides clinical benefit in approximately 50% of patients with unresectable or metastatic DFSP. However, efficacious medical therapies have not been developed for imatinib-resistant DFSP. We established a model of imatinib-resistant DFSP and evaluated CDK4/6 inhibition as a genomically credentialed targeted therapy. DFSP105, an imatinib-resistant human cell line, was established from a fibrosarcomatous DFSP (FS-DFSP), and was studied by SNP arrays and sequencing to identify targetable genomic alterations. Findings were validated in vitro and in vivo, and confirmed in a series including 12 DFSP and 6 FS-DFSP. SNP analysis of DFSP105 revealed a homozygous deletion encompassing CDKN2A and CDKN2B. The resultant p16 loss implicated CDK4/6 as a potential therapeutic target in DFSP. We further demonstrated CDKN2A homozygous deletion in 1 of 12 conventional DFSP and 2 of 6 FS-DFSP, whereas p16 expression was lost in 4 of 18 DFSP. In vitro treatment of DFSP105 with two structurally distinct selective CDK4/6 inhibitors, PD-0332991 and LEE011, led to inhibition of RB1 phosphorylation and inhibition of proliferation (GI50 160 nmol/L and 276 nmol/L, respectively). In vivo treatment of DFSP105 with PD-0332991 (150 mg/kg) inhibited xenograft growth in mice, in comparison with imatinib-treated or -untreated tumors. In conclusion, CDKN2A deletion can contribute to DFSP progression. CDK4/6 inhibition is a preclinically effective treatment against p16-negative, imatinib-resistant FS-DFSP, and should be evaluated as a therapeutic strategy in patients with unresectable or metastatic imatinib-resistant DFSP.
Advances in the Understanding of Germ Cell Tumour Biology

Traditional karyotypic analysis of adult male germ cell tumours (GCTs) performed in this and other laboratories revealed several chromosome abnormalities that may have roles in the aetiology and progression of this disease [1–3].
An open software architecture in a DoD standard GPS receiver

This paper describes an open system software architecture-specifically, the one that would allow the installation of additional operational capability without modifying existing software components-that the DoD easily could introduce into its miniature airborne GPS receiver (MAGR), making capability upgrades simpler, cheaper, and therefore more timely. It describes the existing architecture, identifies problems it creates for the upgrade process, and it describes changes that can be made to create an open system environment. It also identifies the mechanics of adding new capability without modifying the existing operational load module.
Audio thumbnailing of popular music using chroma-based representations

With the growing prevalence of large databases of multimedia content, methods for facilitating rapid browsing of such databases or the results of a database search are becoming increasingly important. However, these methods are necessarily media dependent. We present a system for producing short, representative samples (or "audio thumbnails") of selections of popular music. The system searches for structural redundancy within a given song with the aim of identifying something like a chorus or refrain. To isolate a useful class of features for performing such structure-based pattern recognition, we present a development of the chromagram, a variation on traditional time-frequency distributions that seeks to represent the cyclic attribute of pitch perception, known as chroma. The pattern recognition system itself employs a quantized chromagram that represents the spectral energy at each of the 12 pitch classes. We evaluate the system on a database of popular music and score its performance against a set of "ideal" thumbnail locations. Overall performance is found to be quite good, with the majority of errors resulting from songs that do not meet our structural assumptions.
Debunking the nerd stereotype with pair programming

Our studies show that using pair programming as a structure for incorporating collaboration in the classroom helps increase and broaden participation in computing fields and helps debunk the myth that programmers work alone all the time. It's also a way for students to get a better view of and feel more confident in their preparation for working in the real world. The face of the IT workforce is changing. As the millennial generation makes its way into the working world, the archetype of the nerd as the introverted, obsessed computer programmer must share equal space with the chatty, social software engineer.
Comparative Effects of Formalin and Salt Treatments on Hatch Rate of Koi Carp Eggs

Abstract The efficacy of sodium chloride was compared to that of formalin for improving egg hatch rate of koi, domestic mutation of the common carp Cyprinus carpio. Twelve-hour-old fertilized eggs were held in hatching trays and given a 60-min static treatment of 0, 1,000, 2,500, or 5,000 mg sodium chloride/L, or they were treated with formalin at 250 mg/L for 60 min or 1,000 mg/L for 15 min. Mean hatch rates for salt treatments at 1,000 and 2,500 mg/L and formalin treatments at 250 mg/L were 88.7%, 81.6%, and 98.8%, respectively; these rates were significantly higher than the hatch rate for untreated eggs. The mean hatch rate for untreated eggs was 64.0%, which was not significantly different from the rate for eggs treated with formalin at 1,000 mg/L for 15 min. Treatments with salt at 5,000 mg/L resulted in a mean hatch rate of 30.3%.
Movements and burrow use by northern grasshopper mice as a possible mechanism of plague spread in prairie dog colonies

Abstract Northern grasshopper mice (Onychomys leucogaster) have been implicated as a potential reservoir for plague, which causes local extinction of black-tailed prairie dog (Cynomys ludovicianus) colonies. To identify mechanisms by which grasshopper mice could facilitate plague spread, we measured burrow use, movements, and flea burdens of mice in colonies in northern Colorado. At the microhabitat scale, powder-tracked mice (n = 41) used both prairie dog mounds and burrows extensively, entering an average of 5.3 burrows per 100 m traveled. Burrow use did not differ between active and inactive mounds, or vary with mouse age, sex, or reproductive status. Radiotracking revealed that mice occupied larger ranges (X = 3.84 ha) than reported off colonies, which we estimated would overlap 12–23 prairie dog coterie territories. Mice also harbored high flea burdens (8.1 fleas/mouse), including fleas associated with prairie dogs, which we attributed to their frequent use of burrows. Our results support the conten...
Proteomic analysis identifies in vivo candidate matrix metalloproteinase-9 substrates in the left ventricle post-myocardial infarction

Matrix metalloproteinase-9 (MMP-9) deletion has been shown to improve remodeling of the left ventricle post-myocardial infarction (MI), but the mechanisms to explain this improvement have not been fully elucidated. MMP-9 has a broad range of in vitro substrates, but relevant in vivo substrates are incompletely defined. Accordingly, we evaluated the infarct regions of wild-type (wt) and MMP-9 null (null) mice using a proteomic strategy. Wt and null groups showed similar infarct sizes (48+/-3 in wt and 45+/-3% in null), indicating that both groups received an equal injury stimulus. Left ventricle infarct tissue was homogenized and analyzed by 2-DE and MS. Of 31 spot intensity differences, the intensities of 9 spots were higher and 22 spots were lower in null mice compared to wt (all p<0.05). Several extracellular matrix proteins were identified in these spots by MS, including fibronectin, tenascin-C, thrombospondin-1, and laminin. Fibronectin was observed on the gels at a lower than expected molecular weight in the wt group, which suggested substrate cleavage, and the lower molecular weight spot was observed at lower intensity in the MMP-9 null group, which suggested cleavage by MMP-9. Immunoblotting confirmed the presence of fibronectin cleavage products in the wt samples and lower levels in the absence of MMP-9. In conclusion, examining infarct tissue from wt and MMP-9 null mice by proteomic analysis provides a powerful and unique method to identify in vivo candidate MMP substrates.
Optimal light trail design in WDM optical networks

The enabling technology for supporting IP centric traffic over optical transport networks evolves as the amount of traffic grows. In this paper, we first review a recently proposed concept called light trails. Light trails can enable high speed provisioning, accommodate multigranularity traffic, support high data rates and offer a good candidate for carrying IP traffic over optical networks. Next, we focus on light trail design. We propose a two-step approach for solving the light trail design problem. The first step is called traffic matrix preprocessing, it divides single long hop paths into several shorter paths that satisfy the hop-length constraint. In the second step, the light trail design problem is formulated as an integer linear programming (ILP) optimization problem. The results obtained from our experiments show that the resulting light trail network has high wavelength utilization.
Predictors of acute distress among young adults injured by community violence.

Acute reactions to trauma are examined in 267 individuals severely injured via community violence. Respondents were interviewed about pretrauma, peritraumatic, and acute posttraumatic factors. A series of bivariate and multivariate analyses were conducted. We found few factors related to peritraumatic dissociation (PD): only injury severity and neuroticism emerged as multivariate predictors and the effects were small. PD was strongly related to acute PTSD symptoms, and partially mediated the relationship between other factors and acute PTSD and general distress symptoms. Different patterns of predictors emerged for acute PTSD symptoms vis-a-vis general distress symptoms. Future research on predictors of PD is indicated to develop prevention and early intervention programs.
Linking maintenance strategies to performance

Abstract In order to achieve world-class performance, more and more companies are replacing their reactive, fire-fighting strategies for maintenance with proactive strategies like preventive and predictive maintenance and aggressive strategies like total productive maintenance (TPM). While these newer maintenance strategies require increased commitments to training, resources and integration, they also promise to improve performance. This paper reports the results of a study of the relationship between maintenance strategies and performance. Based on the responses from a survey of plant managers and maintenance managers, the analysis shows strong positive relationships between proactive and aggressive maintenance strategies and performance.
EXPERIENCES IN THE DETECTION AND TREATMENT OF PHENYLKETONURIA

Collected experiences in the detection and treatment of phenylketonuria in a large children9s hospital during the past 5 years have been described. Thirty cases of phenylketonuria have been confirmed. Early examination revealed phenylketonuria in three siblings of known cases. One case showing atypical features has been discussed in more detail. Four patients reported "positive to Phenistix" were found to be excreting phydroxy-phenylpyruvic acid. Two other false-positives were shown to be due to histidine derivatives. In an appendix, details are given of a simple routine method for the determination of plasma phenylalanine.
X-ray analysis of electrets

It is proposed to study the mechanism of the formation and decay of electrets in some non-polar inorganic polycrystalline and amorphous dielectrics. The formation of electrets in these materials under different conditions of sample temperatures polarizing fields and cooling rates will be experimentally pursued. The decay of these electrets both in the open circuit and closed circuit conditions are to be observed (with improved methods whenever possible). An extension of the Swann-Gubkin theory to a more elaborate microscopic theory in agreement with the experimental observations will be sought.
Against the Damnatio Memoriae of Regional Identities: José María Sbarbi's Critique of the Homogenization of National Consciousness in Nineteenth-Century Spain

In 1886, Jose Maria Sbarbi published his one-time novel Dona Lucia in which he mocked the vast inadequacies of the Real Academia's twelfth edition of the Diccionario oficial. Within the greater context of Sbarbi's critical writings on national language, this analysis examines the tension present in the novel that arises between official language controlled artificially by the nation-state and the cultural production of inherited and spontaneous language practiced by the people. The former advocated for a homogenized and exclusionary official language centered on Castilian, while the latter was a heterogeneous practice that embraced the essential diversity of the nation. Sbarbi's condemnation of a homogenized national language that excludes peripheral identities and practices takes shape as a form of cultural aphasia among the people who he portrays in his novel through the mental and physical deterioration of the eponymous character.
ANTITRUST IN SOFTWARE MARKETS

The computer and software sector is a tremendously important and visible part of the economy. It is also a sector in which there have long been concerns about monopolization. In the past, these concerns centered on monopolization by IBM. Today, the concerns are with Microsoft, but in many ways they are the same. IBM was accused of attempting to sabotage industry standards in Fortran; Microsoft is accused of sabotaging JAVA. IBM was accused of predatory product pre-announcements; Microsoft has been accused of employing “vaporware” — the tactic of announcing products before they are ready in order to preempt the market — to undercut its competitors. IBM was accused of bundling functionality into its CPUs to reduce the value of peripheral equipment; Microsoft is battling government lawyers over the bundling of Internet Explorer with Windows 95. IBM was accused of manipulating interfaces and refusing to reveal them to competitors; Microsoft is accused of refusing to reveal interfaces to competitors. Both companies entered into consent decrees with the Department of Justice to settle antitrust charges.