cssi/SciSciGPT-SciSciNet huggingface dataset:
Physical Fitness in Preschool and Elementary School-Aged Children

(1984). Physical Fitness in Preschool and Elementary School-Aged Children. Journal of Physical Education, Recreation & Dance: Vol. 55, No. 9, pp. 33-40.
SRD1, a S. cerevisiae gene affecting pre-rRNA processing contains a C2/C2 zinc finger motif.

Abstract The Saccharomyces cerevisiae genes, RRP1 and SRD1, are involved in processing rRNA precursor species to mature rRNAs. We reported previously that the rrp1-1 mutation caused temperature-sensitive lethality, hypersensitivity to aminoglycoside antibiotics, and defective processing of 27S pre-rRNA to 25S and 5.8S mature rRNAs. A second-site suppressor of the rrp1-1 mutation, srd1, corrects all three rrp1 mutant phenotypes. In order to learn more about the roles of the SRD1 and RRP1 genes in rRNA processing, we cloned and characterized the SRD1 gene. We identified an ORF, YCR18C, that complements srd1-2 suppression of rrp1-1. The DNA is physically located at the region of chromosome III where SRD1 has been genetically mapped. SRD1 encodes a putative 225 amino acid, 26 kDa protein containing a C2/C2 zinc finger motif that is also found in some transcription regulators and the eIF-2 beta translation initiating factors. The similarity of SRD1 to transcription regulators led us to test the model that srd1 mutations suppress rrp1 defects by altering the level of the RRP1 transcript. However, we found that SRD1 has no detectable effect on the steady state levels of RRP1 mRNA. We describe alternative models to explain the role of Srd1p in pre-rRNA processing.
Stepped Impedance Resonators for High-Field Magnetic Resonance Imaging

Multi-element volume radio-frequency (RF) coils are an integral aspect of the growing field of high-field magnetic resonance imaging. In these systems, a popular volume coil of choice has become the transverse electromagnetic (TEM) transceiver coil consisting of microstrip resonators. In this paper, to further advance this design approach, a new microstrip resonator strategy in which the transmission line is segmented into alternating impedance sections, referred to as stepped impedance resonators (SIRs), is investigated. Single-element simulation results in free space and in a phantom at 7 T (298 MHz) demonstrate the rationale and feasibility of the SIR design strategy. Simulation and image results at 7 T in a phantom and human head illustrate the improvements in a transmit magnetic field, as well as RF efficiency (transmit magnetic field versus specific absorption rate) when two different SIR designs are incorporated in 8-element volume coil configurations and compared to a volume coil consisting of microstrip elements.
Walter Nord as Intellectual and Pedagogical Hero

This marks the first of a new AMLE feature that will highlight the careers of the annual recipients of the Academy of Management's Distinguished Educator Award. The 2002 recipient was Walter Nord of the University of South Florida.
Critical Velocity of a Superflowing Liquid-Helium Film Using Third Sound

An investigation of the critical velocity of the helium film is made by impressing a third-sound wave (surface ripple with van der Waals restoring force) on a superflowing film. The velocities of the wave are measured traveling upstream and downstream, and the superfluid critical velocity is deduced as ${V}_{c}=\frac{1}{2}({U}_{3 \mathrm{down}}\ensuremath{-}{U}_{3 \mathrm{up}})$.The critical velocity at the lowest temperature (1.25\ifmmode^\circ\else\textdegree\fi{}K) as a function of the film height is found to be close to $\frac{\ensuremath{\hbar}}{2md}$, where $d$ is the film thickness. This is compared with existing theories and is found compatible with the velocity necessary for the stability of a vortex-line-image pair with a separation of $2d$. Disturbing effects produced by the method used to excite the third sound make it impossible to measure the critical velocity at high temperatures. Arguments are advanced for believing that these disturbing effects do not invalidate the low-temperature results. Since the third-sound wave is formed by the longitudinal oscillation of the superfluid component, the observation of the wave in a film which is flowing at the critical velocity indicates the possibility of film velocities in excess of ${V}_{c}$ for measured times $T\ensuremath{\sim}10$ msec, where $T$ is half a third-sound period. This implies that there is a relaxation time $\ensuremath{\tau}$ for the creation of vortices where $\ensuremath{\tau}gT$. From the data, an upper limit is placed on the difference in thickness between the flowing film and a static film.
The influence of rare earth (RE) constituents on the magnetic and optical properties of RE-FeCo thin films

The polar Kerr effect and perpendicular anisotropy of various rare-earth (RE)-FeCo films were measured and were found to have different dependencies upon the RE composition of the films. The polar Kerr effect was found to be largest for those films where Gd dominated the RE composition. Also, the polar Kerr effect was seen to decrease monotonically as increasingly heavy RE elements from Gd to Er dominated the RE composition. The other RE elements in this range are Tb, Dy, and Ho. In contrast, the perpendicular anisotropy of the same films was seen to be largest when Tb dominated the RE composition. The perpendicular anisotropy decreased rapidly when Gd was substituted for Tb and decreased gradually when increasingly heavy RE elements were substituted for Tb. It is also shown that the dependence of the Curie temperature upon RE composition for these RE-FeCo films correlates strongly with the dependence of the Curie temperature upon composition for pure RE alloys over a similar range of elements. >
Acute inpatient rehabilitation after left ventricular assist device implantation for congestive heart failure.

Heart failure affects an estimated 5.7 million Americans, and almost 300,000 people die from heart failure in the United States each year [1]. Patients with end-stage heart failure become severely disabled because of dyspnea at rest or with minimal exertion, despite maximal medical therapy. Symptoms that typify heart failure, including shortness of breath and fatigue, also have been shown to be directly related to abnormalities of skeletal muscle [2]. Present available treatment options for these patients include medications, cardiac transplantation, or placement of a left ventricular assist device (LVAD). An LVAD is a mechanical device that is used to partially or completely replace the function of the left ventricle. It may be used either for a short period before cardiac transplantation as a “bridging therapy” or for a long-term period as a “destination therapy” in patients who are too sick to undergo cardiac transplantation. Long-term use of an LVAD can result in a clinically meaningful survival benefit and an improved quality of life [3]. In general, patients who have undergone placement of an LVAD and are transferred to a rehabilitation unit have significant comorbidities and are severely deconditioned. Although LVAD placement improves cardiac hemodynamics, an immediate impact on the functional ability of the patient does not occur because of an associated skeletal myopathy. Rehabilitation for these patients is therefore important and challenging. We present our experience with 3 patients who underwent LVAD implantation as a destination therapy and then were admitted for acute inpatient rehabilitation.
Speculations on how Ia antigens (Ir genes) influence the specificity of the immune response.

Summary A model based on different molecular requirements for triggering helper T cells and B cells to proliferate and differentiate is developed. This model offers an explanation for the differing specificity of the T-cell and B-cell receptor repertoires in responding to foreign protein antigens. In addition, it addresses the central paradox in understanding the mechanism by which class II MHC molecules regulate the immune response, namely the problem of how one or a few Ia molecules influence the specificity and degree of immune response to many different complex protein antigens.
A note on generalized Green functions

Abstract A partial-wave expansion in terms of Jost function is obtained for the sngle-particle generalized Green function. Each partial-wave generalized Green function so obtained is in closed form. The results apply at least to Jost function treatable potentials.
Aquaporin channels may modulate ventilator-induced lung injury

Adult Respiratory Distress Syndrome is a disease with functional lung heterogeneity and thus a ventilator-delivered breath may over-distend non-involved areas. In rats we examined ventilator-delivered tidal volume (TV) breaths of 7 and 20 ml/kg on lung water as evidence of lung injury. We examined the role of aquaporins on ventilator-induced lung injury (VILI) by infusing HgCl(2) which inhibits aquaporins by binding cysteine. Wet to dry lung weight ratio (W/D) as evidence of lung water was 4.47+/-0.1 SEM in controls, 4.6+/-0.1 and 5.5+/-0.2 (P<0.05) in rats ventilated at 7 and 20 ml/kg, respectively. Pulmonary artery pressure (PAP) rose from 23+/-1 to 26+/-1 mmHg (P<0.05, n=7) and cardiac output fell from 104+/-2 to 67+/-3 ml/min (P<0.05) in rats ventilated at 20 ml/kg. Left ventricular end diastolic pressure (n=3) was unchanged. Evans Blue dye, an albumin marker, increased from a control 37+/-11 to 97+/-41 mg/g wet lung in TV 20 rats (P<0.05). HgCl(2) infused slowly by tail vein did not significantly raise PAP, but did increase W/D to 6+/-0.2 (P<0.05) in rats ventilated at 20 ml/kg but not at 7 ml/kg. Equimolar cysteine infusions prevented the HgCl(2) from increasing the W/D above that seen with TV 20 ml/kg. Thus ventilation with TV of 20 ml/kg produced a protein-rich lung edema. Aquaporin channels may have a protective effect in VILI.
In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase

Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase, which like O6MeGT have cysteines in their active sites, were not inhibited by acetaldehyde at the levels that inhibited O6MeGT. Disulfiram, an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitory effect of ethanol in vivo. These results indicate that the inhibitory effect of ethanol on O6MeGT activity is mediated primarily via its metabolite, acetaldehyde.
Stationary solutions for the Saffman-Taylor problem with surface tension

We report a one-parameter family of solutions for the problem of the motion of an interface between a viscous and a nonviscous two-dimensional fluid. The solutions have the interface moving uniformly while the viscous fluid has a nontrivial potential flow. In an alternative interpretation, the existence of gravitational forces in the plane allow the interface to be at rest while the fluid is in motion. This family of solutions is a generalization of a solution reported previously [L. P. Kadanoff, Phys. Rev. Lett. 65, 2986 (1990)]. The solutions presented here are found to be related to the traveling-wave solutions of the ``Harry Dym equation,'' which is a completely integrable nonlinear evolution equation.
A coated piezoelectric crystal detector for the selective detection and determination of hydrogen sulfide in the atmosphere

Abstract A method for the selective detection and determination of hydrogen sulfide in the atmosphere is presented. This method utilizes the reversible adsorption of H 2 S on a piezoelectric quartz crystal coated with an acetone extract of soots resulting from the burning of organochlorine compounds. The extract of a soot prepared from chlorobenzoic acid provided the best substrate. The method is useful in the concentration range 1–60 ppm.
β1 Integrins Mediate Chondrocyte Interaction with Type I Collagen, Type II Collagen, and Fibronectin

Abstract Chondrocytes isolated from the cephalic region of sterna from 14-day-old chick embryos used β1 integrins and required either Mg2+ or Mn2+ for attachment to plates coated with type I collagen, type II collagen, and fibronectin. β1 integrin was concentrated in adhesion plaques of the chondrocytes plated on type I collagen, type II collagen, and fibronectin substrates. Chondrocytes expressed at least 3 α-subunits, including α3, α5, and putative α2. α5, but not α3, had a higher molecular weight in chondrocytes than in fibroblasts. Levels of α3 and α5 were about 25-30% of that in fibroblasts. When the chondrocytes were cultured in the presence of ascorbate in suspension, the cells aggregated into clusters. This aggregation was dependent on β1 integrin and type II collagen.
Form and materiality in interaction design: a new approach to HCI

This paper is motivated by the increasing significance of form in design and use of interactive artifacts. The objective of this paper is to conceptualize what we mean by form in the context of interaction design and HCI research and how we can approach it in regard to emerging type of digital materiality. To do this, we first examine conceptual dimensions of form in interactive artifacts through the lens of three existing perspectives with their respective focus on: material, meaning, and making. We then apply these perspectives in our analysis of specific forms of interactive artifacts. Based on this analysis, we suggest a model of four different types of forms: the cognitive, embodied, expressive, and exploratory forms. Reflecting on this model, we propose form-driven interaction design research with its epistemological and methodological implications.
Natural Energy Decomposition Analysis: Extension to Density Functional Methods and Analysis of Cooperative Effects in Water Clusters

Natural energy decomposition analysis (NEDA) is a method for partitioning molecular interaction energies into physically meaningful components, including electrical interaction, charge transfer, and core repulsions. The method is a numerically stable procedure that was originally developed for analyzing Hartree−Fock (HF) wave functions based on the localized orbital description of natural bond orbital analysis. In this work, we extend NEDA to treat charge densities from density functional theory (DFT) calculations, replacing the intermolecular exchange (EX) component of the HF analysis with an exchange-correlation (XC) component. DFT/NEDA is applied to hydrogen bonding interactions and cooperative effects in water clusters. Electrical interactions and charge transfer contribute importantly to hydrogen bonding. Comparison of HF and DFT results reveals that the exchange and correlation effects of DFT slightly enhance the extent of charge transfer and core repulsions in the water clusters. Cooperative stabil...
Molecular orbital theory for pentagonal bipyramidal seven-coordinate complexes. Application to V(CN)74−

Abstract The bonding in pentagonal bipyramidal seven-coordinate complexes is described in terms of molecular orbitals. An SCCC MO calculation was performed for V(CN) 7 4− , and the charge transfer spectrum related to the derived MO scheme. Interactions between adjacent equatorial ligands produce effects not seen in complexes of other geometries.
Lack of correlation between direct and indirect measurements of arterial pressure in unanaesthetized rats.

The tail-cuff method for measuring blood pressure in awake rats, while used as a standard procedure, is not as reliable as is often assumed. Tail-cuff measurements made daily in trained, unanaesthetized rats with chronically implanted aortic catheters did not correlate significantly with simultaneously-recorded intra-arterial pressure. On the other hand, correlation between direct and indirect measurements improved when rats were anaesthetized with ether. Constriction of the tail artery during measurement of arterial pressure could account for the lack of correlation. To examine this possibility, simultaneous measurements were made in unanaesthetized rats after intraperitoneal injection of pressor doses of noradrenaline. During the first 20 min, elevation of arterial pressure caused by injected noradrenaline was clearly evident with either method of measurement. After this, in most experiments, tail pressure either diminished, or could not be detected, while intra-arterial pressure remained high. When sympathetic vasomotor activity was increased in anaesthetized rats by bilateral carotid occlusion, similar results were obtained. These findings indicate that tail-cuff measurements are not valid in certain circumstances in unanaesthetized rats.
The health and management of poultry production

The poultry industry in the USA is a fully integrated system of animal agriculture. Each company has control over the bird husbandry and health management aspects of production, including the use of antimicrobial agents. The three segments of the industry-broiler chickens, turkeys, and layer chickens-have few antibiotics available for the therapeutic treatment of bacterial diseases. Prior to approval of the fluoroquinolones, tetracyclines were the major antibiotics approved for the treatment of the most economically important disease in broiler chickens and turkeys, Escherichia coli airsacculitis. This resulted in levels of resistance to the tetracyclines in clinical E. coli isolates in excess of 90%. The integrated nature of the poultry industry lends itself well to preventive medicine utilizing the tools of biosecurity and vaccination. Therefore, very few flocks of birds require antibiotic therapy. When a flock must be treated, the poultry veterinarian will usually base the recommendation of the drug to use on culture and antibiogram results.
Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex with syndecan-4 in 70 kDa dextran-containing endocytic vesicles. FGF2 and syndecan-4 but not dextran endocytosis were blocked by the dominant negative Rac1 while amiloride and the dominant-negative Cdc42 blocked internalization of dextran in addition to FGF2 and syndecan-4. Taken together, these results demonstrate that FGF2 endocytosis requires syndecan-4 clustering-dependent activation of Rac1 and the intact CDC42-dependent macropinocytic pathway.
Epithelial antimicrobial defence of the skin and intestine

Surface tissues of the body such as the skin and intestinal tract are in direct contact with the external environment and are thus continuously exposed to large numbers of microorganisms. To cope with the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins that directly kill or inhibit the growth of microorganisms. In this Review, we highlight new advances in our understanding of how epithelial antimicrobial proteins protect against pathogens and contribute to microbiota-host homeostasis at the skin and gut mucosae. Further, we discuss recent insights into the regulatory mechanisms that control antimicrobial protein expression. Finally, we consider how impaired antimicrobial protein expression and function can contribute to disease.
The pharmaceutical value of marine biodiversity for anti-cancer drug discovery

Abstract Marine biodiversity is a resource of enormous importance to human societies that provides critical ecosystem services. Economic valuation of some services has been utilized to promote conservation initiatives by revealing a tangible and causative link between biodiversity declines and economic losses. Other ecosystem services have eluded valuation, including the value of the sea as a repository of novel pharmaceuticals. Here, we provide the first global estimate of the number, source and market value of undiscovered oncology drugs based on empirical data, industry statistics and conservative modelling assumptions. We report US$563 billion–5.69 trillion attributable to anti-cancer drugs of marine origin pending discovery, revealing a new and substantial at-risk ecosystem service value. Our model predicted 253,120–594,232 novel chemicals in marine organisms; 90.4–92.6% of these compounds remain undiscovered. A total of 55 to 214 new anti-cancer drugs were predicted to reach the market sourced primarily from animal phyla (Chordata, Mollusca, Porifera, and Byrozoa) and microbial phyla (Proteobacteria and Cyanobacteria). While no single aspect of extractive marine resource value should be relied upon to account for the opportunity costs of conservation initiatives, the application of valuation models to ecosystem services further reveals the true, irreversible economic cost of habitat degradation and biodiversity declines.
Studies of the Performance of Multi-Unit Impact Dampers Under Stochastic Excitation

The performance of particle dampers whose behavior under broadband excitations involves internal friction and momentum transfer is a highly complex nonlinear process that is not amenable to exact analytical solutions. While numerous analytical and experimental studies have been conducted over many years to develop strategies for modeling and controlling the behavior of this class of vibration dampers, no guidelines currently exist for determining optimum strategies for maximizing the performance of particle dampers, whether in a single unit or in arrays of dampers, under random excitation. This paper focuses on the development and evaluation of practical design strategies for maximizing the damping efficiency of multi-unit particle dampers under random excitation, both the stationary and nonstationary type. High-fidelity simulation studies are conducted with a variable number of multi-unit dampers ranging from 1 to 100, with the magnitude of the "dead-space" nonlinearity being a random variable with a prescribed probability distribution spanning a feasible range of parameters. Results of the computational studies are calibrated with carefully conducted experiments with single-unit/single-particle, single-unit/multi-particle, and multiple-unit/multi-particle dampers. It is shown that a wide latitude exists in the trade-off between high vibration attenuation over a narrow range of damper gap size versus slightly reduced attenuation over a much broader range. The optimum configuration can be achieved through the use of multiple particle dampers designed in accordance with the procedure presented in the paper. A semi-active algorithm is introduced to improve the rms level reduction, as well as the peak response reduction. The utility of the approach is demonstrated through numerical simulation studies involving broadband stationary random excitations, as well as highly nonstationary excitations resembling typical earthquake ground motions.
On using a traveling-wave resonator for high-power testing of millimeter-wave ECH components

A traveling-wave resonator may have many times the power supplied by a microwave source, making it possible to test components at a much higher power than would otherwise be available. Described here is a numerical study of a low-power traveling-wave resonator to consider some of the problems encountered in such high-power testing.
Efficient synthesis and anion recognition of a colorimetric preorganized tripodal thiourea compound

A preorganized colorimetric tripodal thiourea receptor was synthesized in high yield utilizing a thiol-ene reaction as a primary step. The interaction of the receptor with dihydrogen phosphate, acetate, chloride, and fluoride anions was investigated using UV–vis. and 1H NMR spectroscopic titration techniques. The binding stoichiometry of the receptor with dihydrogen phosphate and acetate was found to be 1:2, and 1:1 with chloride and fluoride. The binding constants for the receptor and dihydrogen phosphate, acetate, chloride, and fluoride were determined using HypNMR2008 and HypSpec.
Linear scaling approaches to quantum macromolecular similarity: evaluating the similarity function

The evaluation of the electron density based similarity function scales quadratically with respect to the size of the molecules for simplified, atomic shell densities. Due to the exponential decay of the function's atom-atom terms most interatomic contributions are numerically negligible on large systems. An improved algorithm for the evaluation of the Quantum Molecular Similarity function is presented. This procedure identifies all non-negligible terms without computing unnecessary interatomic squared distances, thus effectively turning to linear scaling the similarity evaluation. Presented also is a minimalist dynamic electron density model. Approximate, single shell densities together with the proposed algorithm facilitate fast electron density based alignments on macromolecules.
Flexible Multistage Bayesian Models for Use in Conceptual Design

During conceptual design, designers need tools to help improve design decisions and reduce design times. We are working to develop techniques to create Bayesian surrogate models that respond to designers’ needs during conceptual stages of the design process. Bayesian surrogate models give analytical form to the overall performance of a system and can evolve along with the design. Bayesian surrogate models provide a mathematically rigorous framework in which computational models can be updated based on previous outcomes. In this paper, we present techniques that allow the addition or suppression of parameters without discarding previously obtained information. We also present a case study that illustrates how a surrogate model is constructed in stages when parameters are added or suppressed during the design process. Visualization tools, such as plots of the main effects of parameters, can be derived from surrogate models. These tools can be used to provide knowledge about the parameters that influence the design. Finally, a design problem is used to illustrate how Bayesian surrogate models can inform the designer about tradeoffs that would not be apparent from simulation data alone.Copyright © 2002 by ASME
Effect of Financial Incentives to Physicians, Patients, or Both on Lipid Levels: A Randomized Clinical Trial

Importance Financial incentives to physicians or patients are increasingly used, but their effectiveness is not well established. Objective To determine whether physician financial incentives, patient incentives, or shared physician and patient incentives are more effective than control in reducing levels of low-density lipoprotein cholesterol (LDL-C) among patients with high cardiovascular risk. Design, Setting, and Participants Four-group, multicenter, cluster randomized clinical trial with a 12-month intervention conducted from 2011 to 2014 in 3 primary care practices in the northeastern United States. Three hundred forty eligible primary care physicians (PCPs) were enrolled from a pool of 421. Of 25 627 potentially eligible patients of those PCPs, 1503 enrolled. Patients aged 18 to 80 years were eligible if they had a 10-year Framingham Risk Score (FRS) of 20% or greater, had coronary artery disease equivalents with LDL-C levels of 120 mg/dL or greater, or had an FRS of 10% to 20% with LDL-C levels of 140 mg/dL or greater. Investigators were blinded to study group, but participants were not. Interventions Primary care physicians were randomly assigned to control, physician incentives, patient incentives, or shared physician-patient incentives. Physicians in the physician incentives group were eligible to receive up to $1024 per enrolled patient meeting LDL-C goals. Patients in the patient incentives group were eligible for the same amount, distributed through daily lotteries tied to medication adherence. Physicians and patients in the shared incentives group shared these incentives. Physicians and patients in the control group received no incentives tied to outcomes, but all patient participants received up to $355 each for trial participation. Main Outcomes and Measures Change in LDL-C level at 12 months. Results Patients in the shared physician-patient incentives group achieved a mean reduction in LDL-C of 33.6 mg/dL (95% CI, 30.1-37.1; baseline, 160.1 mg/dL; 12 months, 126.4 mg/dL); those in physician incentives achieved a mean reduction of 27.9 mg/dL (95% CI, 24.9-31.0; baseline, 159.9 mg/dL; 12 months, 132.0 mg/dL); those in patient incentives achieved a mean reduction of 25.1 mg/dL (95% CI, 21.6-28.5; baseline, 160.6 mg/dL; 12 months, 135.5 mg/dL); and those in the control group achieved a mean reduction of 25.1 mg/dL (95% CI, 21.7-28.5; baseline, 161.5 mg/dL; 12 months, 136.4 mg/dL; P P = .002). Conclusions and Relevance In primary care practices, shared financial incentives for physicians and patients, but not incentives to physicians or patients alone, resulted in a statistically significant difference in reduction of LDL-C levels at 12 months. This reduction was modest, however, and further information is needed to understand whether this approach represents good value. Trial Registration clinicaltrials.gov Identifier:NCT01346189
Secondary myelodysplastic syndrome in a patient with Philadelphia-positive acute lymphoblastic leukemia after achieving a major molecular response with hyperCVAD plus imatinib mesylate

The addition of imatinib to high-intensity chemotherapy has improved the outcome of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, the possible long-term side effects of this combination are not yet known. Development of new clonal abnormalities in complete cytogenetic remission after treatment with imatinib has been reported in patients with chronic myeloid leukemia but not in patients with Ph-positive ALL. Here, we present a patient with Ph-positive ALL who received hyperCVAD plus imatinib and achieved hematologic, cytogenetic, and major molecular responses. The patient then developed myelodysplastic syndrome and solitary central nervous system relapse of ALL.
Analytic 3-D eddy current model of a finite width conductive plate including edge-effects

This paper presents a new eddy current modeling approach in which the edge field contribution for a finite width conducting plate is accounted for. The 3-D steady-state analytic eddy current model accounts for the source field contributions from oscillatory as well as translational velocity motional effects. The paper discusses the modeling inaccuracies caused by neglecting the source field contributions on the edges of the conductive plate. The new modeling approach is validated by comparing the analytic calculations with a 3-D steady-state finite element analysis model.
Determinants within the Turret and Pore-Loop Domains of KCNQ3 K+ Channels Governing Functional Activity

KCNQ1–5 (Kv7.1–7.5) subunits assemble to form a variety of functional K+ channels in the nervous system, heart, and epithelia. KCNQ1 and KCNQ4 homomers and KCNQ2/3 heteromers yield large currents, whereas KCNQ2 and KCNQ3 homomers yield small currents. Since the unitary conductance of KCNQ3 is five- to 10-fold greater than that of KCNQ4 or KCNQ1, these differences are even more striking. To test for differential membrane protein expression, we performed biotinylation and total internal reflection fluorescence imaging assays; however, both revealed only small differences among the channels, leading us to investigate other mechanisms at work. We probed the molecular determinants governing macroscopic current amplitudes, with focus on the turret and pore-loop domains of KCNQ1 and KCNQ3. Elimination of the putative N289 glycosylation site in KCNQ1 reduced current density by ∼56%. A chimera consisting of KCNQ3 with the turret domain (TD) of KCNQ1 increased current density by about threefold. Replacement of the proximal half of the TD in KCNQ3 with that of KCNQ1 increased current density by fivefold. A triple chimera containing the TD of KCNQ1 and the carboxy terminus of KCNQ4 yielded current density 10- or sixfold larger than wild-type KCNQ3 or KCNQ1, respectively, suggesting that the effects on current amplitudes of the TD and the carboxy-terminus are additive. Critical was the role of the intracellular TEA+-binding site. The KCNQ3 (A315T) swap increased current density by 10-fold, and the converse KCNQ1 (T311A) swap reduced it by 10-fold. KCNQ3 (A315S) also yielded greatly increased current amplitudes, whereas currents from mutant A315V channels were very small. The KCNQ3 (A315T) mutation increased the sensitivity of the channels to external Ba2+ block by eight- to 28-fold, consistent with this mutation altering the structure of the selectivity filter. To investigate a structural hypothesis for the effects of these mutations, we performed homology modeling of the pore region of wild-type and mutant KCNQ3 channels, using KvAP as a template. The modeling suggests a critical stabilizing interaction between the pore helix and the selectivity filter that is absent in wild-type KCNQ3 and the A315V mutant, but present in the A315T and A315S mutants. We conclude that KCNQ3 homomers are well expressed at the plasma membrane, but that most wild-type channels are functionally silent, with rearrangements of the pore-loop architecture induced by the presence of a hydroxyl-containing residue at the 315 position “unlocking” the channels into a conductive conformation.
Unchecked CD70 expression on T cells lowers threshold for T cell activation in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by premature immune aging with accumulation of degenerate T cells deficient for CD28. Gene expression profiling of CD4(+)CD28(-) and CD4(+)CD28(+) T cells to discover disease-promoting activities of CD28(-) T cells identified expression of CD70 as a most striking difference. Hence, CD70 was significantly more expressed in CD4 T cells from RA patients compared with age-matched controls (p < 0.006). The underlying mechanism was a failure to repress CD70 expression after activation-dependent induction. This defect in RA was not related to differential promoter demethylation. CD70 on bystander CD4(+)CD28(-) T cells functioned by lowering the threshold for T cell activation; admixture of CD4(+)CD28(-) T cells augmented TCR-induced responses of autologous naive CD4(+)CD28(+) T cells, particularly of low-avidity T cells. The data support a model in which CD70 expressed on T cells causes degeneracy in T cell responses and undermines tolerance mechanisms that normally control T cell autoreactivity.
The Therapeutic use of a new Potassium-Sparing Diuretic, Amiloride, and a Converting Enzyme Inhibitor, Mk-421, in Preventing Hypokalemia Associated with Primary and Secondary Hyperaldosteronism

This presentation is a summary of our recent clinical studies on the therapeutic use of a new potassium-sparing diuretic, amiloride, and a converting enzyme inhibitor, MK-421, in preventing hypokalemia associated with primary and secondary hyperaldosteronism. These drugs are quite different in their physiologic action but they both may be effective in preventing the potassium depletion associated with increased aldosterone production. Amiloride, which blocks the sodium channels in distal renal tubular cells, was administered to 10 patients with primary hyperaldosteronism and five patients with Bartter's syndrome (secondary hyperaldosteronism). Amiloride, at doses of 10-40 mg/day, increased mean plasma potassium levels in both primary hyperaldosteronism (3.2-4.5 mEq/L) and, to a lesser extent, in Bartter's syndrome (2.5-3.6 mEq/L). The blood pressure fell slightly but significantly in primary hyperaldosteronism (171/112 vs 150/97 mm Hg) and remained unchanged in Bartter's syndrome (116/80 vs 117/71 mm Hg). The plasma renin activity and plasma aldosterone rose in primary aldosteronism (PRA 0.39-2.21 ng A1/m1/h and PA 28.4-54.3 ng/d1); but in Bartter's syndrome, the PRA declined (25.3-11.9 ng A1/m1/h) and the PA rose (19.5-38.0 ng/d1). The discrepancy in the PRA between primary aldosteronism and Bartter's syndrome may be due to the effects of potassium repletion on suppressing renin and stimulating aldosterone; while in primary aldosteronism, a mild diuretic effect could explain the rise in PRA. In both of these disorders, despite the rise in plasma potassium levels, amiloride produced a counter-therapeutic rise in PA which could potentiate further potassium losses. Therefore, we undertook a study to evaluate the prevention of diuretic-induced hypokalemia and secondary hyperaldosteronism using a new converting enzyme inhibitor, MK-421. Eighteen normal subjects were randomized into three groups receiving either (1) hydrochlorothiazide alone (50 mg/day), (2) MK-421 alone (10 mg/day), or (3) hydrochlorothiazide (50 mg/day) plus MK-421 (10 mg/day). Although MK-421 did not prevent diuretic-induced hypokalemia or hyperaldosteronism in the first week, after that time hypokalemia was reversed and ASR returned to normal. In these studies, it therefore appears that while potassium-sparing diuretics may remain the medical mainstay in treating primary aldosteronism, new converting enzyme inhibitors such as MK-421 may be more effective in treating secondary hyperaldosteronism, since potassium levels can be normalized without increasing aldosterone secretion.
Modal properties and modal control in vertically emitting annular Bragg lasers.

The modal properties, including the resonant vertical radiation, of a type of laser structures based on the annular Bragg resonance (ABR) are studied in detail. The modal threshold gains and the resonance frequencies of such lasers are obtained from the derived governing characteristic equation. Two kinds of ABR lasers, one with a π/2 phase shift in the outer grating and the other without, are analyzed. It is numerically demonstrated that, it’s possible to get a large-area, high-efficiency, single defect mode lasing in ABR lasers if we choose the kind without a π/2 phase shift in the outer grating and also a device size smaller than a critical value.
Monolithically integrated Mach-Zehnder interferometer wavelength converter and widely tunable laser in InP

The first monolithically integrated widely tunable wavelength converter, consisting of a sampled-grating distributed-Bragg-reflector laser (SGDBR) and an SOA-based Mach-Zehnder interferometer, is reported. The integration process requires only a single regrowth step. Static extinction ratios (electrical/optical) better than 18 dB and 13 dB, respectively, were measured over a 22-nm wavelength tuning range. Digital wavelength conversion at bit rate of 2.5 Gb/s was demonstrated to be error free, with 2.6-dB power penalty.
ENaC Proteolytic Regulation by Channel-activating Protease 2

Epithelial sodium channels (ENaCs) perform diverse physiological roles by mediating Na+ absorption across epithelial surfaces throughout the body. Excessive Na+ absorption in kidney and colon elevates blood pressure and in the airways disrupts mucociliary clearance. Potential therapies for disorders of Na+ absorption require better understanding of ENaC regulation. Recent work has established partial and selective proteolysis of ENaCs as an important means of channel activation. In particular, channel-activating transmembrane serine proteases (CAPs) and cognate inhibitors may be important in tissue-specific regulation of ENaCs. Although CAP2 (TMPRSS4) requires catalytic activity to activate ENaCs, there is not yet evidence of ENaC fragments produced by this serine protease and/or identification of the site(s) where CAP2 cleaves ENaCs. Here, we report that CAP2 cleaves at multiple sites in all three ENaC subunits, including cleavage at a conserved basic residue located in the vicinity of the degenerin site (α-K561, β-R503, and γ-R515). Sites in α-ENaC at K149/R164/K169/R177 and furin-consensus sites in α-ENaC (R205/R231) and γ-ENaC (R138) are responsible for ENaC fragments observed in oocytes coexpressing CAP2. However, the only one of these demonstrated cleavage events that is relevant for the channel activation by CAP2 takes place in γ-ENaC at position R138, the previously identified furin-consensus cleavage site. Replacement of arginine by alanine or glutamine (α,β,γR138A/Q) completely abolished both the Na+ current (INa) and a 75-kD γ-ENaC fragment at the cell surface stimulated by CAP2. Replacement of γ-ENaC R138 with a conserved basic residue, lysine, preserved both the CAP2-induced INa and the 75-kD γ-ENaC fragment. These data strongly support a model where CAP2 activates ENaCs by cleaving at R138 in γ-ENaC.
Acquisition of High-Level Mupirocin Resistance and Its Fitness Cost among Methicillin-Resistant Staphylococcus aureus Strains with Low-Level Mupirocin Resistance

We investigated whether methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates with low-level mupirocin resistance can serve as recipients of a pSK41-like plasmid conferring high-level mupirocin resistance without substantial fitness cost. Our results suggest that acquisition of the plasmid conferring high-level mupirocin resistance was not necessarily associated with fitness cost in some MRSA recipients with low-level mupirocin resistance.
Reduced-order unsteady aerodynamic models at low Reynolds numbers

In this paper we develop reduced-order models for the unsteady lift on a pitching and plunging aerofoil over a range of angles of attack. In particular, we analyse the pitching and plunging dynamics for two cases: a two-dimensional flat plate at using high-fidelity direct numerical simulations and a three-dimensional NACA 0006 aerofoil at using wind-tunnel measurements. Models are obtained at various angles of attack and they are verified against measurements using frequency response plots and large-amplitude manoeuvres. These models provide a low-dimensional balanced representation of the relevant unsteady fluid dynamics. In simulations, flow structures are visualized using finite-time Lyapunov exponents. A number of phenomenological trends are observed, both in the data and in the models. As the base angle of attack increases, the boundary layer begins to separate, resulting in a decreased quasi-steady lift coefficient slope and a delayed relaxation to steady state at low frequencies. This extends the low-frequency range of motions that excite unsteady effects, meaning that the quasi-steady approximation is not valid until lower frequencies than are predicted by Theodorsen’s classical inviscid model. In addition, at small angles of attack, the lift coefficient rises to the steady-state value after a step in angle, while at larger angles of attack, the lift coefficient relaxes down to the steady-state after an initially high lift state. Flow visualization indicates that this coincides with the formation and convection of vortices at the leading edge and trailing edge. As the angle of attack approaches the critical angle for vortex shedding, the poles and zeros of the model approach the imaginary axis in the complex plane, and some zeros cross into the right half plane. This has significant implications for active flow control, which are discussed. These trends are observed in both simulations and wind-tunnel data.
Effects of Ethylenediamine Tetracetic Acid (EDTA) on Platelet Structure

The anticoagulant, EDTA, is known to produce changes in the external contour of platelets. In the present investigation the fine structural alterations which develop in EDTA platelets were examined in the electron microscope. Platelets exposed to EDTA at 37° C. lose their disc shape and become irregularly swollen with multiple pseudopods. This external transformation is identical to the change which occurs in platelets exposed to ADP, thrombin, or low temperature. Internal changes in EDTA platelets, however, are markedly different from those which occur under the influence of aggregating agents or cold. The differences indicate that the effects of EDTA on platelet shape are not due to dispersal of marginal band microtubules or to the trigging of an internal wave of contraction. Chelation of membrane calcium by EDTA appears to cause marked irregularities in the platelet wall and massive swelling of the canalicular system. Swelling of internal channals is the dominant alteration in EDTA platelets, and this change appears ultimately to be related to the breakdown of platelet granules.
The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction.

Bony fishes represent the largest vertebrate class and are a very diverse animal group. This chapter provides a thorough review of the available scientific literature on the thyroid system in these important vertebrate animals. The molecular components of the hypothalamic-pituitarythyroid (HPT) axis in this group correspond closely to those of mammals. The thyroid tissue in the fishes is organized as diffuse follicles, with a few exceptions, rather than as an encapsulated gland as is found in most other vertebrate species. The features of this diffuse tissue in fishes are reviewed with an emphasis on feedback relationships within the HPT axis, the molecular biology of the thyroid system in fishes, and comparisons versus the thyroid systems of other vertebrate taxa. A review of the role of thyroid hormone in fish development and reproduction is included. Available information about the HPT axis in fishes is quite detailed for some species and rather limited or absent in others. This review focuses on species that have been intensively studied for their value as laboratory models in assays to investigate disruption in normal function of the thyroid system. In addition, in vitro and in vivo assay methods for screening chemicals for their potential to interfere with the thyroid system are reviewed. It is concluded that there are currently no in vitro or in vivo assays in fish species that are sufficiently developed to warrant recommendation for use to efficiently screen chemicals for thyroid disruption. Methods are available that can be used to measure thyroid hormones, although our ability to interpret the causes and implications of potential alterations in T4 or T3 levels in fishes is nonetheless limited without further research.
Fibroblasts From Longer-Lived Species of Primates, Rodents, Bats, Carnivores, and Birds Resist Protein Damage

Species differ greatly in their rates of aging. Among mammalian species life span ranges from 2 to over 60 years. Here, we test the hypothesis that skin-derived fibroblasts from long-lived species of animals differ from those of short-lived animals in their defenses against protein damage. In parallel studies of rodents, nonhuman primates, birds, and species from the Laurasiatheria superorder (bats, carnivores, shrews, and ungulates), we find associations between species longevity and resistance of proteins to oxidative stress after exposure to H(2)O(2) or paraquat. In addition, baseline levels of protein carbonyl appear to be higher in cells from shorter-lived mammals compared with longer-lived mammals. Thus, resistance to protein oxidation is associated with species maximal life span in independent clades of mammals, suggesting that this cellular property may be required for evolution of longevity. Evaluation of the properties of primary fibroblast cell lines can provide insights into the factors that regulate the pace of aging across species of mammals.
From Brain to Mind: Using Neuroscience to Guide Change in Education. James E. Zull. Sterling, VA: Stylus Publishing, LLC, 2011. 294 pp. $75.00; $14.99 (paperback).

“If the brain is a physical organ of the body, will it also weaken from disuse?” asks James Zull in the introduction of his book, From Brain to Mind: Using Neuroscience to Guide Change in Education...