cssi/SciSciGPT-SciSciNet huggingface dataset:
Investigations into calcium-dependent membrane association of 15-lipoxygenase-1: Mechanistic roles of surface-exposed hydrophobic amino acids and calcium

Abstract Among mammalian lipoxygenases the 15-lipoxygenase-1 is somewhat special because of its capability of oxygenating complex lipid-protein assemblies (biomembranes, lipoproteins) and previous investigations have implicated calcium in enzyme/membrane interaction. We investigated the mechanism of calcium-dependent membrane association and obtained the following results. (i) Membrane binding of 15-lipoxygenase-1 involves electrostatic forces as well as hydrophobic interactions of solvent-exposed apolar amino acids (Tyr15, Phe70, Leu71, Trp181, and Leu195) with the hydrophobic core of membrane phospholipids. These sequence determinants of membrane association are clustered at the membrane contact plane of the enzyme that also involves the entrance to the substrate binding pocket. Site-directed mutagenesis of these determinants to negatively charged residues strongly impaired membrane binding. (ii) Calcium at micromolar concentrations (5-50 μm) is required for efficient membrane binding. For direct 15-lipoxygenase/calcium interaction a dissociation constant of 2-5 × 10-4 m was determined (low affinity binding) and we failed to detect high affinity calcium-binding sites at the enzyme. Reversible low affinity calcium binding induces subtle structural alterations of the enzyme, which did not impact catalytic activity. (iii) Increasing calcium concentrations failed to reverse impairment of membrane binding induced by mutagenesis of the sequence determinants indicating the priority of hydrophobic interactions. Taken together these data suggest that 15-lipoxygenase-1 associates to biomembranes primarily via hydrophobic interactions between surface-exposed apolar amino acid side chains and membrane lipids. Calcium supports membrane binding probably by forming salt bridges between the negatively charged head groups of membrane phospholipids and acidic surface amino acids of the membrane contact plane and this interaction might contribute to overcome repulsive forces.
The elementary foundations of spacetime

This paper is an amalgam of physics and mathematical logic. It contains an elementary axiomatization of spacetime in terms of the primitive concepts of particle, signal, and transmission and reception. In the elementary language formed with these predicates we state AxiomsE, C, andU, which are naturally interpretable as basic physical properties of particles and signals. We then determine all mathematical models of this axiom system; these represent certain generalizations of the standard model. Also, the automorphism groups of the models are determined. Finally we give another physical model and discuss the philosophical implications.
The Gleason Problem for Domains of Finite Type

If Ω is a smoothly bounded pseudoconvex domain of finite type in and if Ω contains the origin, then the maximal ideal of functions in A(Ω) vanishing at the origin is generated by the coordinate functions.
Scriptures, Myths, and Power: The Bible at Work: Introduction

The introduction to Burton Mack's extended conversation with Vincent Wimbush and Institute for Signifying Scripture, Claremont Graduate University. The conversation revolves around the cultural function of the Bible as Christian myth in American society, and the African-American domestication of the Bible as their Scripture. The essay explores the differences between the Bible as myth in the dominant Euro-American tradition, and the Bible as Scripture in African-American experience. Drawing upon the work of Henry Louis Gates, Jr., the concept of "signifying" describes a remarkable linguistic style characteristic of African-American mentality and culture.
Active Documents with Org-Mode

The paper discusses Org-mode. It is a simple, plain-text markup language for hierarchical documents that allows the intermingling of data, code, and prose.
Visual Feeding by Juvenile Bear Lake Sculpin

Abstract Young-of-the-year Bear Lake sculpin Cottus extensus feed throughout the day on benthic invertebrates and cease feeding at night when they migrate to the metalimnion. We investigated their reliance on vision by conducting feeding trials at different light levels in the laboratory. Feeding rate reached a maximum at intermediate light levels (near 1016 photons·m−2·s−1; approximately 1 lux) but decreased as light intensity increased beyond this range. At this maximum rate, the fish fed nine times faster than they were able to feed in the dark, showing that young Bear Lake sculpin rely heavily upon vision to feed. The light intensity at which feeding was greatest corresponded to intensities found on the bottom of Bear Lake (40–60 m) during the day.
Geometric analysis for the size estimation of subsurface delamination in transient electromagnetic response

Detection of subsurface defects (e.g., delamination, cracking) using microwave/radar sensors (e.g., ground penetrating radar or GPR) is an important and promising technique for the effective and efficient maintenance of civil infrastructure. In this technique, reflected and scattered electromagnetic signals are typically collected and used for interpreting the size and property of subsurface damages. The objective of this paper is to investigate the feasibility of using finite measurements in the reflected signal for size estimation, through the geometric analysis of waveform. Simulated transient electromagnetic response was generated by finite difference time domain (FDTD) methods in two dimensional domain. A modulated Gaussian impulse at a center frequency of 3.5 GHz was used as the source. Rectangular delaminations with a width ranging from 3.048 cm to 16.256 cm and a thickness of 0.762 cm were considered. The depth of subsurface delamination was also studied. The curvature of reflected waveforms, obtained by three measurements, was used to correlate with the width of subsurface delamination. A relative width parameter was defined and used in the proposed equations for estimating the delamination width with less than 10% error. It is found that the relative width parameter is linearly proportional to the difference in waveform curvature. The proposed approach is potentially applicable to other subsurface defects with different shapes.
"Equable" climates during Earth history?

Eocene and Cretaceous climate-model experiments demonstrate that regardless of conditions of warm polar oceans, differences in pole-to-equator surface-temperature gradient, or topography, above-freezing surface temperatures in winter for continental interiors at middle to high latitudes cannot be maintained. Continental interiors will have cold winter temperatures, even during globally warm periods, unless currently unrecognized forcing factors influenced past climates. If model simulations of Eocene and Cretaceous climates are accurate, the term "equable," as it applies to paleoclimate, should be reconsidered.
Absorptive bistability in a dielectric sphere

Theoretical results on absorptive optical bistability of micron-sized droplets doped with a saturable absorber are presented. Bistability is observed only when the incident light frequency is near or on a morphology dependent resonance of the sphere. Results on Q-switching are also presented.
Fine-structural changes of the synovial membrane in arthrosis deformans.

The known light microscopic findings in the inner part of joint capsules in arthrosis have largely been verified and in part supplemented by scanning and transmission electron microscopic examinations. Whereas in arthrosis of the hip joint sclerosis of the synovial membrane predominates with atrophy of the layer of lining cells, in arthrosis of the knee joint more polymorphic structures of the surface occur with variable but moderate hyperplasia and hypertrophy of the synovial cells. Inflammatory cell proliferations and infiltrates of the same degree as in non-specific arthritis and rheumatoid arthritis were not observed. Thus, the absence both of characteristic changes of the individual synovial cells and of more extensive inflammatory infiltrates in association with atrophy and sclerosis of the synovial folds may be regarded as an indirect indication of the synovial reaction in arthrosis deformans.
Does douching increase risk for sexually transmitted infections? A prospective study in high-risk adolescents

Objective The objective of the study was to examine the association between douching and 4 sexually transmitted infections (STIs). Study Design We followed up 411 high-risk human immunodeficiency virus-infected and uninfected female adolescents aged 12-19 years over a median 3-year period, both by time from study entry/first STI-free visit until an incident STI for participants who never, intermittently, and always douched and also by reported douching at a given STI-free visit and incidence of STI at the next visit, using adjusted Cox proportional hazards models to calculate hazard ratios (HR). Results The time to STI was shorter for adolescents who always (HR, 2.1; 95% confidence interval [CI], 1.2-3.4) and intermittently (HR, 1.5; 95% CI, 1.0-2.2) douched, compared with never-douchers. An adjusted hazard for STI was 1.8 times larger for always-douchers (95% CI, 1.1-3.1) and 1.4 times larger for intermittent douchers (95% CI, 0.9-2.0), compared with never-douchers. When classifying by follow-up after an STI-free visit, always-douchers had a shorter STI-free time than never-douchers (HR adj , 2.1; 95% CI, 1.5-3.1). Conclusion Counseling to discourage douching may reduce STI risk in adolescents.
Abstract 3097: TSLP regulates expression of genes involved in cell survival in a preclinical xenograft model of CRLF2 B-ALL

A subset of children with B cell precursor acute lymphoblastic leukemia (B-ALL) are at high risk for relapse and death. Gene expression profiles in these high-risk B-ALLs is similar to that of Philadelphia chromosome-positive ALL. Approximately half of these Ph-like B-ALL are characterized by genetic defects resulting in overexpression of CRLF2. This defect occurs 5 times more commonly in Hispanic children than others and thus is a significant biological component of pediatric cancer health disparities. CRLF2, together with the IL-7Rα, forms a receptor complex that is activated by the cytokine, TSLP. Receptor complex activation leads to JAK-STAT5 phosphorylation. The activating JAK mutations found in some CRLF2 B-ALL led to speculation that TSLP stimulation is not a factor in CRLF B-ALL. However, we and others have found that TSLP increases STAT5 phosphorylation in CRLF2 B-ALL cells, including those with JAK defects. Our next step was to evaluate the role of TSLP-CRLF2 interactions in vivo in the human-mouse xenograft model. However, mouse TSLP is species-specific and does not activate the human TSLP receptor complex that includes CRLF2. Thus, traditional xenograft models do not provide the TSLP-CRLF2 interactions that may contribute to high risk CRLF2 B-ALL. We engineered immune-deficient NOD/SCID IL-2Rγ null (NSG) mice to express human TSLP (hTSLP+ mice), as well as control mice that lack the TSLP cytokine (hTSLP- mice). Then we used this hTSLP+/- xenograft model system to evaluate the in vivo effects of TSLP on transplanted CRLF2 B-ALL cells harboring a JAK defect (MUTZ5 cell line). Transplanted mice were euthanized at 5 weeks and bone marrow (BM) was harvested. Evaluation of BM by flow cytometry showed that approximately half of the human leukemia cells were apoptotic in mice without TSLP while apoptosis was virtually absent in CRLF2 B-ALL cells harvested from hTSLP+ mice. Next we used Ingenuity Pathway Analysis to identify functions and pathways regulated by TSLP. Primary CRLF2 B-ALL cells were transplanted into hTSLP+ and hTSLP- mice. Whole genome microarray performed on primary human leukemia cells isolated from BM of xenograft mice identified 280 genes that were upregulated and 281 genes that were downregulated (> 2 fold up or downregulated; p Citation Format: Olivia L. Francis, Ruijun Su, Shannalee R. Martinez, Ineavely Baez, Terry-Ann Milford, Ross Fisher, Christopher L. Morris, Xiaobing Zhang, Valeri Filippov, Sinisa Dovat, Kimberly J. Payne. TSLP regulates expression of genes involved in cell survival in a preclinical xenograft model of CRLF2 B-ALL. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3097. doi:10.1158/1538-7445.AM2014-3097
THE AMERICAN SOLDIER AN ASSESSMENT, SEVERAL WARS LATER

Editor's Note This year marks the fortieth anniversary of the publication of a book of great significance for PUBLIC OPINION QUARTERLY readers: The American Soldier. (The American Soldier itself was part of a larger series, Studies in Social Psychology in World War II, which included an important 1949 volume by Carl Hovland and others on Experiments in Mass Communication and an equally important methodological volume of writings by Louis Guttman, Paul Lazarsfeld, and others, Measurement and Prediction, published one year later.) The range of separate studies reported in The American Soldier, their ingenuity, method of analysis, and theoretical implications, helped establish research on public opinion as an important area for scientific work, as well as signaling the contributions of a remarkable number of social scientists brought together in this unique wartime effort. One of that group, the distinguished sociologist Robin M. Williams, Jr., has agreed to reflect on the importance-then and now-of The American Soldier. We hope that his essay will send our readers back to the original volumes. There is much still to learn from them.
Arginine 165/arginine 277 pair in (S)-mandelate dehydrogenase from Pseudomonas putida: role in catalysis and substrate binding.

(S)-Mandelate dehydrogenase from Pseudomonas putida belongs to a FMN-dependent enzyme family that oxidizes (S)-α-hydroxyacids. Active site structures of three homologous enzymes, including MDH, show the presence of two conserved arginine residues in close juxtaposition (Arg165 and Arg277 in MDH). Arg277 has an important catalytic role; it stabilizes both the ground and transition states through its positive charge as well as a hydrogen bond [Lehoux, I. E., and Mitra, B. (2000) Biochemistry 39, 10055−10065]. In this study, we examined the role of Arg165 and the overall importance of the Arg165/Arg277 pair. Single mutants at Arg165 as well as double mutants at Arg165 and Arg277 were characterized. Our results show that Arg165 has a role similar to, but less critical than, that of Arg277. It stabilizes the transition state through its positive charge and the ground state through a charge-independent interaction, most likely, a hydrogen bond. Though the kcats for the charge-conserved mutants, R165K and R277K,...
Architectural Research: Incorporating Myth and Science

Despite an apparently common assumption that science and myth are totally incompatible approaches to architecture, especially as related to architectural design, I argue that science and myth are both explanations of phenomena, each different, but both valid. Positing the desirability of a research and design process that would take advantage of both approaches, I address the problems of existing conceptual categories and the possible productive relationship between myth and science for architecture. Anthropology is then proposed as a paradigm for an architectural research that could address both science and myth, and this is illustrated with examples of research and design studio instruction.
Wave packet calculations for helium scattering by a xenon monolayer

The interaction of low energy helium atomic beams with a rigid monolayer of xenon atoms was studied with a pseudo spectral wave packet method. The calculated diffraction intensities were compared to experimental scan curve data, finding similar trends in the relative values of the peaks. The calculated elastic diffraction patterns were strongly asymmetric for beams incident along directions other than ΓK and ΓM, supporting the argument that the inelastic scattering will also be very sensitive for experimental angles of incidence which deviate slightly from the high-symmetry directions.
Self-starting additive-pulse mode locking of a Nd:YAG laser

We report additive-pulse mode locking of lamp-pumped Nd:YAG lasers at both 1.06 and 1.32 μm. Under completely self-starting conditions, stable cw mode-locked trains of 6-psec pulses have been achieved at an average output power of 2.4 W.
Protruding domain of capsid protein is necessary and sufficient to determine murine norovirus replication and pathogenesis in vivo.

Human noroviruses (HuNoVs) are the major cause of epidemic, nonbacterial gastroenteritis worldwide. Due to the lack of a tractable model system and the inability to grow HuNoVs in cell culture, factors required for the norovirus (NoV) life cycle and pathogenesis in the host remain largely unknown. The discovery of murine norovirus (MNV) and the development of reverse-genetics systems for this virus provide an opportunity to study these aspects of NoV infection in vitro and in vivo. Previous studies identified a single amino acid at residue 296 in the protruding (P) domain of the capsid protein that is responsible for determining the virulence of the MNV clone MNV1.CW1 in 12956/SvEv background STAT1-deficient (STAT1−/−) mice. In this report, we identified and characterized another determinant of lethality in the P domain that is necessary and sufficient to determine the replication and pathogenesis of the MNV clones MNV1.CW3 and CR6.STL1 in C57BL/6 background STAT1−/− mice. Furthermore, we describe how the role of residue 296 in MNV virulence differs between STAT1−/− mouse strains. We also describe potential interactions between subdomains of the P domain, as well as between other virus elements, which facilitate recovery of MNV using a reverse-genetics system.
Short-Term Consequences of Angiographically-Confirmed Coronary Stent Thrombosis

Objectives To conduct a meta-analysis to quantify the real-world incidence of in-hospital or 30-day death or myocardial infarction (MI), and angiographically-confirmed ST-related treatment costs. Background The short-term clinical and economic consequences of coronary stent thrombosis (ST) are thought to be significant. Methods We searched MEDLINE, Embase and Scopus from January 2000-July 2012 to identify observational/registry studies that evaluated a cohort of ≥25 patients experiencing angiographically-confirmed thrombosis of a drug-eluting or bare-metal stent, required the use of dual-antiplatelet therapy for guideline-recommended durations, and reported incidences of in-hospital or 30-day death or MI and/or ST-related treatment costs. Incidences and costs from each study were pooled using random-effects meta-analysis. Results Twenty-three studies were included. Of the 13 studies reporting in-hospital outcomes, 12 (N=8,832 STs) reported mortality data, with the pooled incidence rate estimated to be 7.9%, 95%CI=5.4%-11.3%, I2=86%. Ten studies (N=1,294 STs) reported 30-day death, with a pooled incidence of 11.6%, 95%CI=8.8%-15.1%, I2=55%. Patients experiencing early ST (within 30-days of implant) had higher in-hospital and 30-day mortality than those experiencing very-late ST (interaction p<0.04 for both). Stent type had no significant effect on in-hospital or 30-day mortality. In the 5 studies (N=542 STs) and 3 studies (N=180 STs) reporting in-hospital and 30-day MI, respectively, the pooled incidence rates were 6.1%, 95%CI=2.1%-16.2%, I2=88% and 9.5%, 95%CI=3.8%-22.0%, I2=65%. One study reported costs associated with ST, estimating the median/patient cost of hospitalization to treat early ST at $11,134 (in 2000US$). Conclusions Regardless of stent type used, the short-term consequences of coronary ST appear significant.
Localization and hormonal regulation of ovarian production of histamine in the sheep

Concentrations of histamine were measured within the follicular wall, follicular fluid and ovarian interstitium throughout the periovulatory period in sheep. Histamine within follicular tissue declined after the onset of the preovulatory surge of luteinizing hormone (LH) and remained low until after ovulation, when levels then increased markedly. Alterations in histamine within the follicular wall were not reflected by corresponding changes within follicular fluid or ovarian interstitium. Release of histamine from tissue during short-term incubation was greatest for follicles obtained after ovulation, which was not influenced by presence of LH in the incubation medium. Luteinizing hormone caused depletion of stores of histamine from the wall of follicles collected before the preovulatory surge of LH. Histamine could act as a paracrine mediator in the follicular mechanisms of ovulation and(or) luteinization.
The effect of dreissenid invasions on chlorophyll and the chlorophyll : total phosphorus ratio in north-temperate lakes

We investigated the effects of dreissenid mussel (Dreissena polymorpha and D. rostriformis bugensis) invasions on the concentrations of chlorophyll a (Chl) and total phosphorus(TP), and the Chl:TP ratio within 27 north-temperate lakes that spanned large gradients in lake size and trophic status, using two approaches: (i) regression analysis and (ii) hierarchical modeling. Overall, Chl declined by 40%–45% after dreissenid invasion and the magnitude of effect was structured by epilimnetic volume within stratified, but not nonstratified (mixed) lakes. Declines in TP over the invasion period were significant only for stratified systems and were smaller (∼16% reduction from pre-invasion values) than for Chl. Across the complete trophic gradient (i.e., among lakes) the regression approach (analysis of covariance) indicated a significant decline in the intercept of the Chl:TP, but not the slope. In contrast, hierarchical modeling indicated a decline in the slope of Chl:TP among lakes between pre- and post-invasi...
Purification and characterization of galacto‐oligosaccharide‐producing β‐galactosidase from Sirobasidium magnum

Galacto-oligosaccharide-producing β-galactosidase from Sirobasidium magnum CBS6803 was purified to homogeneity with a yield of 60% by DEAE-toyopearl, butyl-toyopearl, p-aminobenzyl 1-thio-β-D-galactopyranosidc-agart>se and concanavalin A agarose columns, from a solubilized cell wall preparation. The isoelectric point (pI) of purified (4-galactosidase it-as 3.8, and the relative molecular mass was 67 000 as estimated by SDS gel electrophoresis, and 135 000 as estimated by gel filtration. Optimal β-galactusidase activity was observed at a temperature and pH of 65°C and pH 4.5-55, respectively. The K m values for o-nitrophenyl-β-D-galactopyranoside and lactose were 14.3 and 5.5 mmol 1 -1 , respectively, and the V max , values for these substrates were 33.4 and 94.5 mmol min -1 mg of protein respectively. In addition this enzyme possessed a high level of transgalactosylation activity, and 72 mg ml -1 galacto-oligosaccharide was produced from 200 mg ml -1 lactose.
On the Hamilton-Jacobi-Bellman equations in Banach spaces

This paper is concerned with a certain class of distributed parameter control problems. The value function of these problems is shown to be the unique viscosity solution of the corresponding Hamiltonian-Jacobi-Bellman equation. The main assumption is the existence of an increasing sequence of compact invariant subsets of the state space. In particular, this assumption is satisfied by a class of controlled delay equations.
Discriminative performance by three species of monkeys as a function of trial 1 reward contingency, intertrial interval, and prior test experience

Four naive rhesus, 4 naive stump-tailed, and 6 sophisticated squirrel monkeys received 7-trial object discrimination problems in which a single object was presented as rewarded or nonrewarded on Trial 1. The second trial with 2 objects followed after an intertrial interval (ITI) of either 10, 30, 60, 90, 120, or 150 sec., and the remaining 2-object trials were presented with a constant 10-sec. ITI. In all 3 species and with all ITT’s the nonrewarded Trial 1 condition resulted in markedly better Trial 2 performance than did the rewarded Trial 1 condition; the effect was attenuated on subsequent trials. All species showed a monotonic decline in performance as a function of ITT’s.
Synchronization, chaos, and the breakdown of collective domain oscillations in reaction-diffusion systems

The universal equations describing collective oscillations of the multidomain patterns of small period in an arbitrary d-dimensional reaction-diffusion system of the activator-inhibitor type are asymptotically derived. It is shown that not far from the instability leading to the formation of the pulsating multidomain pattern the oscillations of different domains synchronize. In one dimension standing and traveling waves of the oscillation phase are realized. In addition to these, in two dimensions target and spiral waves of the oscillation phase, as well as spatiotemporal chaos of domain oscillations, are feasible. Further inside the unstable region the collective oscillations break down, so the pulsating multidomain pattern transforms into an irregular pulsating pattern, uniform self-oscillations, or turbulence. The parameter regions where these effects occur are analyzed. The effects of the pattern's disorder are also studied. The conclusions of the analysis are supported by the numerical simulations of a concrete model. The obtained results explain the dynamics of Turing patterns observed in experiments on the chlorite-iodide-malonic acid reaction.
Spectrum of small-scale density fluctuations in tokamaks

The power spectrum of plasma density fluctuations in the range of frequencies of drift waves has been investigated in the Princeton Large Torus tokamak. The results suggest that the observed fluctuations evolve to a strong nonlinear state, and therefore they emphasize the need for a complete nonlinear theory of drift waves in tokamaks to assess their effects on plasma transport.
MO-D-204B-01: Characterizing Uncertainties in Hypoxia Imaging-Based Dose Painting Prescriptions

Purpose: Inadequate characterization of variability from dose escalation models limits the precise definition of dose painting prescriptions. The purpose of this study was to quantify uncertainties in hypoxia imaging‐based prescriptions using an empirically‐driven and patient‐specific model.Materials and Methods: The model coupled an electrochemical formalism, which related Cu‐ATSM (hypoxia surrogate) uptake and pO 2 , with a modified oxygen enhancement ratio (OER) equation to yield non‐uniform dose prescriptions. This methodology was applied to eight head and neck cancer patients who underwent Cu‐ATSM PET/CT scans. Integral dose escalation was determined as a function of tumor hypoxic proportion (HP 2.5 = percent tumor voxels with pO 2 < 2.5 mmHg). Model parameters included intracellular acidity ‐ pH, dose boost as a function of hypoxic proportion ‐ D boost(HP 2.5), max OER ‐ OER max, and half‐max sensitization oxygen tension ‐ P mid. Parameters were varied within published ranges for this patient population, and uncertainties were propagated to variations in the maximum dose heterogeneity (MDH = D max − D min D mean ). Results:Model parameters had differing impact on dose prescription uncertainties. Over the range of pH values [7.1–7.3], variation in MDH was 4 percent (maximum 9 percent). Within the 95 percent confidence intervals of the D boost(HP 2.5) functional fit, variability in MDH was 5 percent (maximum 14 percent). Between the limits of OER max values [1.4–3.0], variation in MDH was 1 percent (maximum 2 percent). From the array of P mid values [2–5 mmHg], variation in MDH forallparameterswas 1 percent (maximum 2 percent). The total variation in MDH for all parameters was 10 percent (maximum 17 percent). Conclusions: Dose prescription variability was on the order of 10 percent. Variations were due primarily to uncertainties in cellular acidity and dose boost functional fit, which are parameters governing calculated oxygen tension distributions. Ultimately, the derivation of a hypoxia imaging‐based prescription function will require fitting model parameters to outcome data in dose escalation clinical trials.
Fracture behavior of vanadium/vanadium silicide in-situ composites

The fracture behavior of V-V{sub 3}Si in-situ composite alloys has been evaluated for intermetallic phase fractions of 30, 50, and 70 volume percent. In addition, the mechanical properties of the ductile constituent in these composites have been evaluated from two alloys containing silicon at its solubility-limit in vanadium at the eutectic temperature and at 1400{degrees}C. The fracture toughness was found to increase monotonically with increasing volume fraction of ductile phase. Fractography has shown evidence of crack bridging by the vanadium solid solution phase and increased ductility within the composite relative to bulk measurements. The toughness results are compared with predictions based on an existing model of ductile-phase toughening using our measurements of component properties.
A Policy for Space Robotics

This paper will briefly summarize the history of robotic systems in space and the technology required. It then outlives some of the problems in the current system, and summarizes a proposed policy statement.
Slow-Electron Mean Free Paths in Aluminum, Silver, and Gold

Beam-attenuation measurements were made on free-standing polycrystalline films of various thicknesses at energies between the work function and several electron volts above. The electron-electron collision mean free paths ${l}_{e}$ were determined by correction of the attenuation lengths for electron-phonon scattering lengths ${l}_{p}$ deduced from the attenuation temperature dependence. Imperfection mean free paths were negligible. The following results were obtained: for aluminum, ${l}_{e}\ensuremath{\sim}50$ \AA{} and ${l}_{p}\ensuremath{\sim}250$ \AA{} near 5 eV above the Fermi level; for gold, $45 \AA{}g{l}_{e}g15 \AA{}$ for energies between 5.5 and 10 eV; and for silver, $42 \AA{}g{l}_{e}g20 \AA{}$ for energies between 5.5 and 8 eV. In the energy range between 5.5 and 7.5 eV, it was found that ${l}_{p}\ensuremath{\sim}250$ \AA{} for gold and ${l}_{p}\ensuremath{\sim}400$ \AA{} for silver. All measured ${l}_{p}$ were only about two-thirds of the value near the Fermi level. Quinn's theory for ${l}_{e}$ in a dense free-electron gas predicts that for aluminum ${l}_{e}\ensuremath{\sim}60$ \AA{} at 5 eV. Exchange corrections in Kleinman's dielectric screening function tend to bring the value closer to the observed one. In silver and gold, considerable interaction of the beam electrons with the $d$ band occurred for which no theory is available as yet. The resulting data were compared with the energy dependence of ${l}_{e}$ deduced semiempirically by Krolikowski and Spicer from the density of states obtained from photoemission experiments. Reasonable agreement with presently available data was observed.
A method for estimating switch-mode power supply size

A method of estimating the physical size and layout of switch-mode power supplies is presented. This method includes analytical expressions for determining the physical size of inductors, capacitors, and transformers. The calculations are based on the black box input-output requirements of the power supply, and can be used to evaluate and compare competing design approaches or topologies. The technique is based on fundamental power supply parameters-power, energy, and electric charge-and avoids needless calculations during the initial estimation stage of a power supply design. Calculations using this estimation technique are presented for buck, forward flyback, and boost regulators. >
Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-B

Objectives. An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-B, VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3). Material and methods. (a) Serum levels of IGF-II, IGF-BP3, VEGF-B (VEGF 165 ) and VEGF-C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75 persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III; 70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t test, chi-square analysis and linear regression analysis were used. Results. (a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P P Conclusion. Serum IGF-II up-regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF-C up-regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF-BP3 and VEGF-B appear to be common markers for all gynecological cancers.
Update on pharmacoeconomics in transplantation.

Purpose—To provide current information on pharmacoeconomic outcomes in transplantation for the past 6 years. Methods—An extensive literature search was undertaken using PubMed and other authenticated Internet sources. Key words used to elicit pertinent studies were “pharmacoeconomics,” “transplantation,” “cost-effectiveness,” “cost-benefit,” “cost-minimization” and “cost-utility” analyses. Studies included in the review contain updated pharmacoeconomic data generated during the past 6 years on economic, clinical, and humanistic outcomes. These data are used to describe and analyze the cost of drug therapy used in transplantation. Results—Background information is included in the review to provide a context from which to evaluate new study material. Data extracted from the studies include significant findings and study limitations. Data were stratified into understanding pharmacoeconomic methods and their application to transplantation, maintenance and induction therapies, and management of and costs associated with adverse events and quality-of-life issues. Conclusions—Continued evolution of pharmacoeconomic analysis is needed so that optimal care can be provided in the most cost-effective manner. Pharmacoeconomic study, done rationally and logically, is an indispensable tool in determining optimal transplantation regimens. (Progress in Transplantation. 2007;17:103-120)
Effectiveness of local anesthesia in pediatric dental practice.

ABSTRACT Background Pain control in dental treatment for children is very important. The purpose of this study is to describe the characteristics of local anesthetic use by pediatric dentists and to examine factors related to its effectiveness in children. Methods The authors observed 361 patients in 17 pediatric dental practices in Washington state while each child received restorative or surgical dental treatment. The authors recorded data concerning local anesthetic use and effectiveness. The children's mean age was 87 months, and 181 (50.1 percent) of the patients were girls. A pediatric dentist observer rated each child's anxiety before the initial injection of local anesthetic and the effectiveness of pain control during restorative treatment. The observing dentist asked the treating dentist about the effectiveness of pain control after completion of treatment. Results Forty-two of 361 children (11.6 percent) were observed to experience ineffective pain control. Fourteen of 17 dentists (82.4 percent) were observed to have at least one patient in whom pain control was ineffective. Lidocaine (2 percent with 1:100,000 epinephrine) was used by 15 of 17 dentists (88.2 percent) and in 312 of 361 cases (86.4 percent). The average amount of agent was one cartridge (36 milligrams of lidocaine). Children who were anxious, who had symptoms before treatment, and who underwent more invasive operative and endodontic procedures were more likely to experience ineffective pain control. Conclusions The data suggest that painful treatment is relatively frequent even in specialized pediatric practice. Variability in general practice is likely to be greater. Clinical Implications The incidence of ineffective pain control may be less if clinicians use methods to reduce anxiety and perioperative infection and symptoms.
Effect of Chemical Additives on Toughening of Fillets of Frozen Alaska Pollack (Theragra chalcogramma)

Fillets of Alaska pollack (Theraga chalcogramma), a gadoid, were treated with solutions of citrate, sodium pyruvate, or H2O2, frozen and stored for 9 wk at -10°C. Protein extractability, texture, cooked moisture content, and activity of trimethylamine oxide demethylase were monitored during storage. None of the treatments slowed normal decline in protein extractability during frozen storage, however, sodium citrate and H2O2 significantly (P < 0.1) inhibited development of dimethylamine (DMA). This inhibition of DMA development did not, however appear to be associated with a decrease in the rate of toughening evidenced in H2O2-treated fillets. Sodium citrate and sodium pyruvate significantly slowed rate of toughening during storage, and this effect may be related to their positive effect on water-holding capacity.
A Head and Neck Surgeon’s Perspective on Best Practices for the Use of PET/CT Scans for the Diagnosis and Treatment of Head and Neck Cancers

Thisbrief reviewpresentsasummary evaluation of relevant, identified literatureaddressing3centralquestions. (1) What is the utility of positron emissiontomographicandcomputed tomographic (PET/CT) scanning in the pretreatment evaluation of patients with head and neck squamous cell carcinoma (HNSCC), including those with an unknown primary? (2) What is the utility of PET/CT scanning in the evaluation of patients with HNSCC with a clinically N0 (cN0) neck based on examinat ion and convent ional imaging? (3) What is the utility and best timing for PET/CT in the posttreatment oncologic surveillance of patients with HNSCC?
Frequent Breastfeeding and Food Refusal Associated with Failure to Thrive A Manifestation of the Vulnerable Child Syndrome

This paper acquaints pediatricians and health care personnel with the triad of poor weight gain, frequent breastfeeding, and food refusal in infants during the second 6 months of life. The histories of six infants aged 8-11 months, with failure to thrive, food refusal, and frequent breastfeeding, are presented. All the mothers were facing significant stresses, which may have decreased their breast milk supply, and were leading them to use breastfeeding for their comfort and/or the comfort of their infant. The infants responded with continued frequent breastfeeding, refusal of complementary foods, and decreased weight gain. These infants fit the characteristics of the vulerable child syndrome. Treatment of these infants required evaluation and treatment of the mothers' psychosocial issues along with a behavioral feeding program. Even with this multidisciplinary approach, these infants showed very slow catch-up growth. Pediatricians and health care personnel should use and build on this information in the evaluation and treatment of infants with similar problems.
A Variant in a MicroRNA Complementary Site in the 3'UTR of the KIT Oncogene Increases Risk of Acral Melanoma

MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma.
A protein interaction surface in nonribosomal peptide synthesis mapped by combinatorial mutagenesis and selection

Nonribosomal peptide synthetases (NRPSs) and polyketide synthases are large, multidomain enzymes that biosynthesize a number of pharmaceutically important natural products. The recognition of biosynthetic intermediates, displayed via covalent attachment to carrier proteins, by catalytic domains is critical for NRPS and polyketide synthase function. We report the use of combinatorial mutagenesis coupled with in vivo selection for the production of the Escherichia coli NRPS product enterobactin to map the surface of the aryl carrier protein (ArCP) domain of EntB that interacts with the downstream elongation module EntF. Two libraries spanning the predicted helix 2 and loop 2/helix 3 of EntB-ArCP were generated by shotgun alanine scanning and selected for their ability to support enterobactin production. From the surviving pools, we identified several hydrophobic residues (M249, F264, and A268) that were highly conserved. These residues cluster near the phosphopantetheinylated serine in a structural model, and two of these positions are in the predicted helix 3 region. Subsequent in vitro studies are consistent with the hypothesis that these residues form a surface on EntB required for interaction with EntF. These results suggest that helix 3 is a major recognition element in EntB-ArCP and demonstrate the utility of selection-based approaches for studying NRPS biosynthesis.
Finite Element Modelling of Micro-cantilevers Used as Chemical Sensors

Nowadays, silicon micro-cantilevers with different geometrical shapes are widely used as micro-electro-mechanical systems and, more recently, as force sensor probes in atomic force microscopy (AFM). During the last ten years, several applications, which include these AFM micrometer-sized cantilevers as mass probes in microbalances or as chemical sensors in chemical micro-system devices, were developed. In the case of complex shapes of cantilevers, where the cross-section is not constant along the cantilever length (case of ?V-shaped? micro-cantilevers), their resonant frequencies can not be analytically calculated. Firstly, in order to validate the accuracy of our FEM approach, we carried out a comparison between analytical, experimental and FEM-computed values of the resonant frequencies for homogenous rectangular shaped micro-cantilevers. Then, we performed a modeling of silicon beams coated with a thin sensitive layer (50 nm of Gold). To precisely calculate the resonant frequencies of these multilayer-cantilevers, the influence of the mesh parameters on the calculated frequencies was strongly investigated. Secondly, the sensitivity of different ?V-shaped? silicon cantilevers was estimated, as a function of their geometrical dimensions and of their mechanical parameters (Young modulus, density). The resonant frequencies of uncoated cantilevers were calculated and compared with the values experimentally determined. Then, a similar approach was employed to predict the sensitivities of such cantilevers recovered with a sensitive layer.
Initial American Experience with Hip Resurfacing Following FDA Approval

In May 2006, the US Food and Drug Administration approved the first metal-on-metal total hip resurfacing. Surgeons wanting to implant this device were required to undergo formal industry-sponsored training before performing their first case and a technical specialist attended their initial 10 cases. Safety surveys were completed on the first 537 cases performed and included patient age, gender, diagnosis, and occurrence of any unexpected events perioperatively or postoperatively. Intraoperative data were available for all 537 cases (100%), hospital discharge and six-week data were available for 524 cases (97.6%), three-month data were available for 523 cases (97.4%), six-month data were available for 509 cases (94.3%) and one-year data were available for 449 cases (83.6%); the mean followup was 10.4 months. We documented adverse events in 40 (32 major, 8 minor) of the 537 cases including nine nerve injuries and eight dislocations. There were 14 component revisions (7.4%) within the first year, including 10 for femoral neck fracture, two for dislocations, and two for acetabular component loosening. Complications were frequently seen among patients older than 55 years of age and in women, emphasizing the importance of appropriate patient selection for the procedure. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
The ECB as a Strategic Actor: Central Banking in a Politically Fragmented Monetary Union

The European Central Bank’s relationship to the national governments of the monetary union was modeled as a contest between fiscal and monetary dominance early in the euro crisis (Buiter 2010, drawing on Sargent and Wallace 1981). This paper shows how strategic behavior helped to shape the timing and substance of ECB policy during 2010-2013 as well as the response of governments. While ex ante bargains between the monetary and fiscal authority can in principle preempt the struggle for dominance, political fragmentation of the euro area prevented such bargains during the crisis. Strategic behavior largely explains the differences in the responses of the ECB, the Federal Reserve and Bank of England to their respective crises and continues to play out as the euro area seeks to complete the architecture of the monetary union. Deflation demonstrates that monetary not fiscal dominance prevails in the euro area, decisively. The ECB Governing Council should now prioritize the objective of raising the rate of inflation in light of this victory.