cssi/SciSciGPT-SciSciNet huggingface dataset:
Velocity structure functions, scaling, and transitions in high-Reynolds-number Couette-Taylor flow.

Flow between concentric cylinders with a rotating inner cylinder is studied for Reynolds numbers in the range $2\ifmmode\times\else\texttimes\fi{}{10}^{3}lRl{10}^{6}$ (Taylor Reynolds numbers, $10l{R}_{\ensuremath{\lambda}}l290)$ for a system with radius ratio $\ensuremath{\eta}=0.724$. Even at the highest Reynolds number studied, the energy spectra do not show power law scaling (i.e., there is no inertial range), and the dissipation length scale is surprisingly large. Nevertheless, the velocity structure functions calculated using extended self-similarity exhibit clear power-law scaling. The structure function exponents ${\ensuremath{\zeta}}_{p}$ fit Kolmogorov's log-normal model within the experimental uncertainty, ${\ensuremath{\zeta}}_{p}=(p/3)[1+(\ensuremath{\mu}/6)(3\ensuremath{-}p)]$ (for $pl~10)$ with $\ensuremath{\mu}=0.27$. These ${\ensuremath{\zeta}}_{p}$ values are close to those found in other flows. Measurements of torque scaling are presented that are an order of magnitude more accurate than those previously reported [Lathrop et al., Phys Rev. A 46, 6390 (1992)]. Measurements of velocity in the fluid core reveal the presence of azimuthal traveling waves up to the highest Reynolds numbers examined. These waves show evidence of a transition at ${R}_{T}=1.3\ifmmode\times\else\texttimes\fi{}{10}^{4}$; this transition was observed previously in measurements of torque, but our wave velocity and wall shear stress measurements provide the first evidence from local quantities of the transition at ${R}_{T}.$ Velocity measurements indicate that at ${R}_{T}$ there is a change in the coherent structures of the core flow; this is consistent with our analyses of the scaling of the torque. Our measurements were made at two aspect ratios, and no significant dependence on aspect ratio was observable for $Rg{R}_{T}.$
Differential stress reduction: preliminary application to an alcohol-abusing population.

This study applied a differential stress reduction paradigm to an alcoholic population. The paradigm was tested by designing stress management procedures to match alcoholics’ locus of control. Subjects were 55 participants in an alcohol dependency treatment program at a Veterans Administration Medical Center. Three-channel assessment of general anxiety with seven separate measures was conducted; data were collected at pretesting, posttesting, and at an 8-week follow-up. A two-factor design was used, incorporating multivariate analyses of covariance. Findings supported the hypothesis that matching the treatment control orientation with trainee locus of control enhances outcome. Results also showed a significant difference in outcome between types of locus of control, with internal locus of control subjects performing better. There were no significant differences in the treatment group comparisons.
Remarks on Grandi’s Comments

This note is a reply to some of Giovanni Grandi’s comments on my paper “Berkeley’s Contingent Necessities.”
Lower Blood Pressure Goals in High-Risk Cardiovascular Patients: Are They Defensible?

This review highlights the paucity of data that support actively decreasing blood pressures (BP) to a level of less than 130/80 mm Hg. Although the data support a lower cardiovascular (CV) event rate with this lower level of pressure in high-risk CV people, early aggressive intervention to prevent levels from going above this mark prevent development of worsening atherosclerosis. Although no trial will ever prove this concept of prevention, common sense and multiple animal experiments support it. Most patients should have their systolic BP reduced to levels well below 140 mm Hg approaching 130 mm Hg, not 140 mm Hg.
PERCEPTION OF DANGER BY POLICE OFFICERS

Corrigan (1977) argued that the greater the danger perceived by a police officer, the greater will be his use of authority which will lead ~n time to a sense of social isolation and subsequently enhance feelings of occupational solidarity. Corrigan dcvised a 44 item questionnaire to measure the variables danger, authority, social isolation, and occupational solidarity. Scale dimensions were operationalized as follows: dangcr consisted of: ( 1 ) fear of physical injury, ( 2 ) fear of injury to self-esteem, and ( 3 ) fear of unknown injury; authority consisted of: ( 1 ) perception of power, ( 2 ) desire and need ro control others' behavior, and ( 3 ) ability to exercise verbal and physical control; social isolation consisted of: ( 1 ) separativeness, ( 2 ) physical inability to socialize outside of occupation, and ( 3 ) monopolization of time; occupational solidarity consisted of: ( 1 ) group cohesiveness, ( 2 ) loyality (mutual assistance and secrecy), and ( 3 ) job identification. Data for 61 police officers in a medium-sized city showed that perception of danger correlated .46 (Pearson) with use of authority, which in turn correlated .21 with feelings of social isolation; the larter correlated .35 with feelings of occupational solidarity. The present study was done to replicate these findings for municipal police officers, drawn from police officers attending law enforcement seminars and in an eastern seaboard state. Corrigan's (1977) questionnaire was given to 75 male officers (M age = 33.5 yr., SD = 5.9; M length of service = 108.1 mo., SD = 62.6). Rank, age, and length of service were uncorrelated with danger, authority, social isolation, and occupational solidarity. The only significant correlations obtained were between perception of danger and the use of authority (Pearson rn = 0.37, two-tailed p < .01) and between the perception of danger and feelings of social isolation ( r = 0.42, two-tailed p < ,001). These findings do not replicate Corrigan's (1977) results. except both of these studies showed that police officers who perceived danger more do use their authority more. Reasons for the discrepancy in the two studies are presently obscure. The present results indicate that municipal police officers who perceive a great deal of danger in their jobs tend to use their authority more and tend also to feel more socially isolated. Their feelings a b u t the job are quite likely to affect both behavior on the job and living off the job.
Three-dimensional analysis of regional cardiac function: a model of rabbit ventricular anatomy

The three-dimensional geometry and anisotropic properties of the heart give rise to nonhomogeneous distributions of stress, strain, electrical activation and repolarization. In this article we review the ventricular geometry and myofiber architecture of the heart, and the experimental and modeling studies of three-dimensional cardiac mechanics and electrophysiology. The development of a three-dimensional finite element model of the rabbit ventricular geometry and fiber architecture is described in detail. Finally, we review the experimental results, from the level of the cell to the intact organ, which motivate the development of coupled three-dimensional models of cardiac electromechanics and mechanoelectric feedback.
Variation in thermal tolerance of North American ants.

Abstract Changing climates are predicted to alter the distribution of thermal niches. Small ectotherms such as ants may be particularly vulnerable to heat injury and death. We quantified the critical thermal maxima of 92 ant colonies representing 14 common temperate ant species. The mean CT max for all measured ants was 47.8 °C (±0.27; range=40.2–51.2 °C), and within-colony variation was lower than among-colony variation. Critical thermal maxima differed among species and were negatively correlated with body size. Results of this study illustrate the importance of accounting for mass, among and within colony variation, and interspecific differences in diel activity patterns, which are often neglected in studies of ant thermal physiology.
Anisotropic superconducting and normal state magnetic properties of single crystals of RNi*2*B*2*C compounds (R = Y, Gd, Dy, Ho, Er, and Tm)

The interaction of superconductivity with magnetism has been one of the most interesting and important phenomena in solid state physics since the 1950`s when small amounts of magnetic impurities were incorporated in superconductors. The discovery of the magnetic superconductors RNi{sub 2}B{sub 2}C (R = rare earth, Y) offers a new system to study this interaction. The wide ranges of superconducting transition (T{sub c}) and antiferromagnetic (AF) ordering temperatures (T{sub N}) (0 K {le} T{sub c} {le} 16 K, 0 K {le} T{sub N} {le} 20 K) give a good opportunity to observe a variety of interesting phenomena. Single crystals of high quality with appropriate size and mass are crucial in examining the anisotropic intrinsic properties. Single crystals have been grown successfully by an unusual high temperature flux method and characterized thoroughly by X-ray, electrical transport, magnetization, neutron scattering, scanning electron microscopy, and other measurements.
An Examination of Trispiral Hinges Suitable for Use in ABS-Based Rapid Prototyping of Compliant Mechanisms

This paper examines the use of a trispiral hinge in compliant mechanisms generated by low cost, ABS-based, rapid prototyping machines. Hinges are examined to establish relationships between hinge geometry parameters (core radius, spiral angle, spiral pitch, and spiral thickness) and hinge performance (in-plane rotation, off-axis stability). A number of joint parameter combinations are found that provide good joint rotation characteristics with minimal off-axis instability. These joints allow for joint rotations up to ±90 degrees from a neutral position with little parasitic motion during the rotation. The implementation of these joints is further examined through the building and testing of fully compliant mechanisms based on the Roberts and Hoeken approximate straight-line mechanism geometries. The fully compliant mechanisms are shown to have the ability to closely recreate the approximate straight-line motion of the equivalent 4-bar chains. As such, the trispiral joint provides promise as a joint type that can be used effectively in conjunction with fused deposition modeling (FDM) machines that use ABS as the build material.Copyright © 2014 by ASME
High-Energy Neutron Scattering and the Mihara-Puff Theory of the Structure Factor for Liquid Helium-Four

The ostensible correctness of the Mihara-Puff theory of the structure factor for liquid helium-four and well-known sum-rule expressions are combined to suggest two limiting forms for the dynamic structure factor. One of them is exact in the limit $k\ensuremath{\rightarrow}\ensuremath{\infty}$ and has the form proposed by Hohenberg and Platzman. We show that it should provide information about Bose condensation if inelastic neutron scattering can be done for $kg40$ ${\mathrm{\AA{}}}^{\ensuremath{-}1}$. The other is a simple phenomenological form which applies to the range $3 {\AA{}}^{\ensuremath{-}1}lkl8 {\AA{}}^{\ensuremath{-}1}$ and is shown to describe successfully the scattering experiments of Cowley and Woods.
On-line monitoring of the keyhole welding pool in variable polarity plasma arc welding

AbstractThis paper presents a technique to monitor the weld penetration in real time by the front-side image sensing of the keyhole welding pool in variable polarity plasma arc welding (VPPAW) of a 6061 aluminium alloy. A novel optical system is developed to acquire the keyhole welding pool images from two sides of the plasma arc welding torch. The geometric sizes of the visible keyhole can be accurately obtained by using the developed image-processing algorithm. The variation in sizes of the visible keyhole has a close relationship with the real diameter of the keyhole. An artificial neural network (ANN) model is established to describe the relationship between the keyhole diameter and the geometrical sizes of the keyhole welding pool obtained from the image.
Updates on chemical and biological research on botanical ingredients in dietary supplements

Increased use of dietary supplements is a phenomenon observed worldwide. In the USA, more than 40% of the population recently reported using complementary and alternative medicines, including botanical dietary supplements. Perceptions that such dietary supplements are natural and safe, may prevent disease, may replace prescription medicines, or may make up for a poor diet, play important roles in their increased use. Toxicity of botanical dietary supplements may result from the presence of naturally occurring toxic constituents or from contamination or adulteration with pharmaceutical agents, heavy metals, mycotoxins, pesticides, or bacteria, misidentification of a plant species in a product, formation of electrophilic metabolites, organ-specific reactions, or botanical-drug interactions. The topics discussed in this review illustrate several issues in recent research on botanical ingredients in dietary supplements. These include (1) whether 1,3-dimethylamylamine is a natural constituent of rose geranium (Pelargonium graveolens), (2) how analysis of the components of dietary supplements containing bitter melon (Momordica charantia) is essential to understanding their potential biological effects, and (3) how evolving methods for in vitro studies on botanical ingredients can contribute to safety evaluations. The virtual explosion in the use of botanical ingredients in hundreds of products presents a considerable challenge to the analytical community, and the need for appropriate methods cannot be overstated. We review recent developments and use of newer and increasingly sensitive methods that can contribute to increasing the safety and quality of botanical ingredients in dietary supplements.
The Effect of Rotor Blade Thickness and Surface Finish on the Performance of a Small Axial Flow Turbine

An experimental investigation was conducted to determine the effect of blade profile inaccuracies and surface finish on the aerodynamic performance of a 11.13 cm tip diameter turbine. The as-received cast rotor blades had a significantly thicker profile than the design intent and a fairly rough surface finish. Stage test results showed an increase of one point in efficieny by smoothing the surface finish and another three points by thinning the blade profiles to near the design profile. Most of the performance gain between the as-cast thick and the thinned rotor blades both with the same surface finish, was attributed to reduced trailing edge losses of the recontoured blades.
Reactivity and regulation: The impact of Mary Rothbart on the study of temperament

Through her theoretical and empirical work, Mary Rothbart has had a profound impact on the scientific understanding of infant and child temperament. This special issue honors her contributions through the presentations of original, contemporary studies relevant to three primary themes in Rothbart's conceptual approach: the expansive scope and empirically-derived structure of temperament, the importance of considering developmental change, and the interplay of reactive and regulatory processes. In addition to summarizing these themes, this introductory article acknowledges the ways Mary has spurred progress in the field through methodological advances, institutional service, and pedagogy. Copyright © 2008 John Wiley & Sons, Ltd.
Using Elastic Light Scattering of Red Blood Cells to Detect Infection of Malaria Parasite

To develop noninvasive diagnosis of malaria, we studied the light-scattering pattern of healthy and 2% Plasmodium falciparum malaria parasitized red blood cells. By measuring the wavelength-dependent scattering at discrete angles of both forward and backward directions, we found that the signal can clearly distinguish between healthy and ring stage infected red blood cells. In particular, we demonstrated the first backward scattering measurement, which enables elastic light scattering as a promising noninvasive diagnostic tool for malaria.
The Influence of Grain Boundaries on Radiation-Induced Point Defect Production in Materials: A Review of Atomistic Studies

Radiation-induced defects cause severe degradation of materials properties during irradiation that can ultimately cause the material to fail. Consequences of these defects include swelling, embrittlement, and undesirable phase transformations. Nanocrystalline materials, which contain a high density of grain boundaries, have demonstrated enhanced radiation tolerance compared to large grain counterparts under certain conditions. This is because, as has long been recognized, grain boundaries can serve as defect sinks for absorbing and annihilating radiation-induced defects. Increasingly, researchers have examined how grain boundaries influence the direct production of defects during collision cascade, the origin of the radiation-induced defects. In this review article, we analyze the computational studies in this area that have been performed during the past two decades. These studies examine defect production near grain boundaries in metallic, ionic, and covalent systems. It is found that, in most systems, grain boundaries absorb more interstitials than vacancies during the defect production stage. While this is generically true of most boundaries, the detailed interaction between defects and grain boundaries does depend on boundary atomic structure, the stress state near the boundary, cascade-boundary separation, and materials properties. Furthermore, the defect distribution near boundaries is qualitatively different from that in single crystals, with the former often exhibiting larger vacancy clusters and smaller interstitial clusters than the latter. Finally, grain boundaries that are damaged after cascades have occurred exhibit different interaction behavior with defects than their pristine counterparts. Together, these atomistic simulation results provide useful insight for both developing higher-level modeling of defect evolution at long timescales and how interfaces influence radiation damage evolution.
American Indian grand families: a qualitative study conducted with grandmothers and grandfathers who provide sole care for their grandchildren.

A qualitative study was conducted to determine the rationale for 31 American Indian grandparents’ who provide sole care of their grandchildren, the impact of historical trauma on their decision making process in accessing services, the value of American Indian Child Welfare policies in addressing care issues, and custody status of the grand families. Indian Outreach Workers, Community Health Representatives, Elder Program Directors, and tribal community leaders were key in the recruitment of participants. The grandparents were informed of the purpose of the study and participated in face-to-face, paper and pencil, individual interviews. The subjects included 29 grandmothers and two grandfathers; age 43–86 years, with 20 who lived off reservation land and 11 who lived on reservation land in Michigan. A phenomenological approach of the “world of the lived experience” informed the design of the study. The researchers recorded the subjects’ responses via field notes, conducted a comparison of responses to assess internal reliability, and entered the responses into the qualitative data analysis Nvivo program. Findings included; (1) reasons for providing sole care of grandchildren (2) stressors and rewards of providing sole care (3) grandparents decisions affected by historical traumas which focused on the boarding school issues and the removal of children from their homes due to cultural differences causing a reluctance to seek and access national and state programs (4) grandparents preference was to seek and access services provided by their Tribal Nations, and/or American Indian urban agencies (5) most lacked legal custodial status which is an indicator the grandparents’ may have benefited from knowledge of the Indian Child Welfare Act (ICWA).
The Smallest Thiolated Gold Superatom Complexes

The superatom concept of metallic cluster valence is based on the electron-shell model as first proposed to explain the special stability of certain metal-atom clusters generated in the gas phase. It accounts for the magic-number series 2, 8, 18, 34, 58, ... by shell-closing of the superatom orbitals 1S, 1P, 1D, .... Recently, the superatom-complex concept has been introduced to explain the compositions of high-yield gold-cluster compounds, especially Au25(SR)18− and Au102(SR)44 (with -SR being a thiolate group), corresponding to the magic numbers of 8 and 58, respectively. Surprisingly, no thiolated gold cluster accounting for the first closing (electron count 2) has yet been determined. Structure-bonding considerations lead us to propose Au12(SR)9+ as the superior candidate for the smallest thiolated gold superatom. This cluster features an octahedron core covered by three RS(AuSR)2 motifs. It has a unique C3 axis, is chiral, and possesses ideal aurophilic interactions and, therefore, should exist in na...
Microwave spectral studies of rotational isomerism in substituted ethanethiols: 2-Aminoethanethiol and 2-chloroethanethiol

Abstract Microwave spectra were observed and analyzed for 2-aminoethanethiol and 2-chloroethanethiol. The amino compound exists in two gauche rotameric conformations, one exhibiting an intramolecular SH⋯N hydrogen bond. The hydrogen-bonded conformer lies higher in energy by 274 ± 90 cal mole −1 and has the following rotational constants (in MHz): A = 12 040.1 ± 11.3, B = 3352.24 ± 0.03, and C = 2881.99 ± 0.03. For the non-hydrogen-bonded conformer the rotational constants (in MHz) are A = 11 929.9 ± 10.2, B = 3395.01 ± 0.03, and C = 2877.82 ± 0.03. Dipole moment measurements for the H-bond conformer led to μ a = 2.68 D, μ b = 0.88 D, and μ c = 0.37 D, while for the non-H-bond form the values are μ a = 1.51 D, μ b = 0.0 D, and μ c = 0.62 D. In the case of chloroethanethiol, the only assigned spectral lines were the unresolved J → J + 1 a -type bands of a trans conformation. For this molecule the combination rotational constant B + C has the value 2955.17 ± 0.02 MHz for the 35 Cl species and 2879.73 ± 0.02 MHz for the 37 Cl species.
Comparative Effects of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor on Coronary Collateral Development and the Arterial Response to Injury

Background We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for ≥4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell–specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. Methods and Results Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n=9), VEGF 0.72 mg (n=9), or saline (n=10) as a daily left atrial bolus (days 10 to ...
Potentiometric Method for the Assay of L-Aspartase Enzyme Activity

Abstract A new sensitive, accurate and reproducible method has been developed for the assay of L-aspartase (aspartate ammonia-lyase, EC 4.3.1.1) activity. Ammonium ion selective elctrodes were used to measure the increase in activity of ammonium ion produced during the deamination of L-aspartate, a reaction catalyzed by L-aspartase. The sensitive electrode membrane was prepared by immobilizing nonactin in polyvinyl chloride (PVC). Our potentiometric studies indicate an optimum substrate concentration of 0.05 M for L-aspartate and an optimum pH of 8.4. Also, a linear calibration curve of the electrode response towards enzyme activity was obtained in which activity units as low as 0.007 units/ml were detected. These findings were confirmed using spectrophotometric techniques. The increase in absorbance at 240 nm was used to measure the increase in fumarate during the deamination of L-aspartate. The interference from potassium ion was eliminated by dialyzing the enzyme preparation against water.
Activation of skeletal adenyl cyclase by parathyroid hormone in vitro.

The effect of parathyroid hormone on adenyl cyclase from fetal rat calvaria was tested. Adenyl cyclase was assayed in particulate fractions from this tissue by measuring conversion of ATP-α-32P to 3′,5′-AM32P. Parathyroid hormone caused rapid stimulation of enzyme activity; the degree of stimulation was related to the log of hormone concentration. Adenyl cyclase in calvaria was not sensitive to a variety of hormones known to stimulate this enzyme in other tissues. The enzyme was sensitive to parathyroid hormone in skeletal and renal cortical tissue but not in heart, brain, spleen, thyroid, adrenal, or fat cells. Parathyroid hormone and sodium fluoride also stimulated theenzyme in calcified bone from adult rats. Neither parathyroid hormone nor thyrocalcitonin affected the activity of cyclic nucleotide phosphodiesterase in skeletal tissue, nor did thyrocalci tonin affect adenyl cyclase. These observations provide the basis for the concept that a single type of interaction between hormone and enzyme bound to...
Regulation of bradykinin-induced cyclic AMP response by quinacrine and prostaglandin E2 and F2α in human synovial fibroblasts

Bradykinin induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the release of [3H] arachidonic acid and [3H]-E prostaglandins from human synovial fibroblasts prelabeled in their phospholipids. Both these bradykinin-induced reactions are inhibited by quinacrine, an inhibitor of phospholipase A activity. The cyclic AMP response of human synovial fibroblasts to bradykinin is potentiated by prostaglandin E2 and inhibited by prostaglandin F2α. These data emphasize the critical role of the prostaglandin system in reactions induced by bradykinin and suggest mechanisms by which inflammatory reactions due to bradykinin may be modulated.
An automated prompting system for smart environments

The growth in popularity of smart environments has been quite steep in the last decade and so has the demand for smart health assistance systems. A smart home-based prompting system can enhance these technologies to deliver in-home interventions to a user for timely reminders or a brief instruction describing the way a task should be done for successful completion. This technology is in high demand with the desire for people who have physical or cognitive limitations to live independently in their homes. In this paper, we take the approach to fully automating a prompting system without any predefined rule set or user feedback. Unlike other approaches, we use simple off-the-shelf sensors and learn the timing for prompts based on real data that is collected with volunteer participants in our smart home testbed.
A Bayesian Procedure for Mastery Decisions Based on Multivariate Normal Test Data.

A Bayesian framework for making mastery/nonmastery decisions based on multivariate test data is described in this study. Overall, mastery is granted (or denied) if the posterior expected loss associated with such action is smaller than the one incurred by the denial (or grant) of mastery. An explicit form for the cutting contour which separates mastery and nonmastery states in the test score space is given for multivariate normal test scores and for a constant loss ratio. For multiple cutting scores in the true ability space, the test score cutting contour will resemble the boundary defined by multiple test cutting scores when the test reliabilities are reasonably close to unity. For tests with low reliabilities, decisions may very well be based simply on a suitably chosen composite score.
Clinical evaluation of 1,3-butadiene neurotoxicity in humans.

1,3-Butadiene is one of the most commonly produced chemicals in the United States. It is also a known human and animal carcinogen. Information about 1,3-butadiene induced neurotoxicity is scarce. I...
The Agrarian History of England and Wales. Volume VII, 1850–1914 . Edited by E. J. T. Collins. Cambridge: Cambridge University Press, 2000. Pp. xl, 2277. $295.00.

Excess, we learned as children in Glasgow, was the defining characteristic of Americans: big country, big cars, food served by the bucket, big talk, Texas, CGE models. Eccentricity identified the English: bird watching, Bovril, train spotting, the Archers, bus spotting, Women's Institute Teas, the standard-of-living debate. This book represents an interesting merger of all that is American with all that is English. With 2,317 pages devoted to English agrarian history between 1850 and 1914, completed 44 years after the series was initiated, and published only after the deaths of two of the principal authors, it screams American-style excess. But the loving care devoted to duck decoys, the Large Black Pig Society, Church of England music, sand dunes, malaria, Cupiss's Constitution Balls, golf courses, agrarian utopianism, ruderal [sic] habitats, the Rational Dress Society, and much, much more betrays an endearing eccentricity that could only be English.
A hot oxidant, 3-NO2Y122 radical, unmasks conformational gating in ribonucleotide reductase

Escherichia coli ribonucleotide reductase is an α2β2 complex that catalyzes the conversion of nucleotides to deoxynucleotides and requires a diferric-tyrosyl radical (Y(•)) cofactor to initiate catalysis. The initiation process requires long-range proton-coupled electron transfer (PCET) over 35 A between the two subunits by a specific pathway (Y(122)(•)→W(48)→Y(356) within β to Y(731)→Y(730)→C(439) within α). The rate-limiting step in nucleotide reduction is the conformational gating of the PCET process, which masks the chemistry of radical propagation. 3-Nitrotyrosine (NO(2)Y) has recently been incorporated site-specifically in place of Y(122) in β2. The protein as isolated contained a diferric cluster but no nitrotyrosyl radical (NO(2)Y(•)) and was inactive. In the present paper we show that incubation of apo-Y(122)NO(2)Y-β2 with Fe(2+) and O(2) generates a diferric-NO(2)Y(•) that has a half-life of 40 s at 25 °C. Sequential mixing experiments, in which the cofactor is assembled to 1.2 NO(2)Y(•)/β2 and then mixed with α2, CDP, and ATP, have been analyzed by stopped-flow absorption spectroscopy, rapid freeze quench EPR spectroscopy, and rapid chemical quench methods. These studies have, for the first time, unmasked the conformational gating. They reveal that the NO(2)Y(•) is reduced to the nitrotyrosinate with biphasic kinetics (283 and 67 s(-1)), that dCDP is produced at 107 s(-1), and that a new Y(•) is produced at 97 s(-1). Studies with pathway mutants suggest that the new Y(•) is predominantly located at 356 in β2. In consideration of these data and the crystal structure of Y(122)NO(2)Y-β2, a mechanism for PCET uncoupling in NO(2)Y(•)-RNR is proposed.
The Organizational Life Cycle: Issues in the Creation, Transformation, and Decline of Organizations

The article reviews the book “The Organizational Life Cycle: Issues in the Creation, Transformation, and Decline of Organizations,” by John R. Kimberly and Robert H. Miles.
Study of possible complex formation between macromolecules and certain pharmaceuticals. III. Interaction of polyethylene glycols with several organic acids.

A study has been made of the complexing behavior of high molecular weight polyethers with a number of pharmaceutical compounds. By means of solubility procedures it has been found that although pentobarbital and barbital have little or no tendency to complex with polyethylene glycols, phenobarbital forms stable and stoichiometric molecular compounds with these macromolecular substances. Phase analysis indicates that one phenobarbital molecule is bound by two ethylene oxide units of the polyether chains. It is also shown by another phase analytical method that phenolic compounds are bound by the polyethers in the same fashion, the higher molecular weight polymers exhibiting greater complexing tendency than those of lower degrees of polymerization. Experimental data obtained on the various acids investigated indicate that these compounds are only weakly bound.
Glucose Oxidation Modulates Anoikis and Tumor Metastasis

Cancer cells exhibit altered glucose metabolism characterized by a preference for aerobic glycolysis or the Warburg effect, and the cells resist matrix detachment-induced apoptosis, which is called anoikis, a barrier to metastasis. It remains largely unclear whether tumor metabolism influences anoikis and metastasis. Here we show that when detached from the matrix, untransformed mammary epithelial cells undergo metabolic reprogramming by markedly upregulating pyruvate dehydrogenase (PDH) kinase 4 (PDK4) through estrogen-related receptor gamma (ERRγ), thereby inhibiting PDH and attenuating the flux of glycolytic carbon into mitochondrial oxidation. To decipher the significance of this metabolic response, we found that depletion of PDK4 or activation of PDH increased mitochondrial respiration and oxidative stress in suspended cells, resulting in heightened anoikis. Conversely, overexpression of PDKs prolonged survival of cells in suspension. Therefore, decreased glucose oxidation following cell detachment confers anoikis resistance. Unlike untransformed cells, most cancer cells demonstrate reduced glucose oxidation even under attached conditions, and thus they inherently possess a survival advantage when suspended. Normalization of glucose metabolism by stimulating PDH in cancer cells restores their susceptibility to anoikis and impairs their metastatic potential. These results suggest that the Warburg effect, more specifically, diminished glucose oxidation, promotes anoikis resistance and metastasis and that PDKs are potential targets for antimetastasis therapy.
Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension.

Study objectives: Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition. Design: Open-label study. Setting: Medical ICUs of three tertiary care hospitals in New England. Patients: Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH. Interventions: Patients were administered inhaled nitric oxide (iNO), IV epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil. Results: iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP ( SE) was greater than after 1 h of sildenafil alone (44.6 3.8 to 40.6 3.9 mm Hg, p 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance. Conclusions: A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil. (CHEST 2006; 129:417–425)
Disruption of the X-loop turn of the prion protein linked to scrapie resistance.

The prion diseases are a class of neurodegenerative diseases caused by the misfolding and aggregation of the prion protein (PrPC) into toxic and infectious oligomers (PrPSc). These oligomers are critical to understanding and combating these diseases. Differences in the sequence of PrP affect disease susceptibility, likely by shifting the tolerance of the protein for adaptation to PrPSc conformations and/or the recognition event between PrPSc and PrPC prior to conversion of the PrPC. We selected two sets of PrPSc-resistant mutant sequences for solvated atomistic molecular dynamics simulation to investigate the structural basis of resistance. The first group involved mutation in the X-loop (residues 164-171) resulting from selective breeding of sheep. The second group included eight mutants in mice identified by random mutagenesis targeting helix C followed by screening in cell cultures. Multiple simulations were performed of 14 different mutant and control constructs under different pH conditions for a total of 3.6 μs of simulation time. The X-loop formed a stable turn at neutral pH in wild-type PrP from both species. PrPSc-resistant mutations disrupted this turn even though only one of the mutants is in the X-loop. The X-loop is compact and buried in our previously described spiral models of PrPSc-like oligomers. On the basis of the findings presented here and in the context of the spiral oligomer model, we propose that expansion of the X-loop disrupts protofibril packing, providing a structural basis for resistance.
Cytosolic Localization of Listeria monocytogenes Triggers an Early IFN-γ Response by CD8+ T Cells That Correlates with Innate Resistance to Infection

IFN-γ is critical for innate immunity against Listeria monocytogenes ( L. monocytogenes ), and it has long been thought that NK cells are the major source of IFN-γ during the first few days of infection. However, it was recently shown that a significant number of CD44 high CD8 + T cells also secrete IFN-γ in an Ag-independent fashion within 16 h of infection with L. monocytogenes . In this report, we showed that infection with other intracellular pathogens did not trigger this early IFN-γ response and that cytosolic localization of Listeria was required to induce rapid IFN-γ production by CD44 high CD8 + T cells. Infection of C57BL/6 mice with an Escherichia coli strain expressing listeriolysin O (LLO), a pore-forming toxin from L. monocytogenes , also resulted in rapid IFN-γ expression by CD8 + T cells. These results suggest that LLO expression is essential for induction of the early IFN-γ response, although it is not yet clear whether LLO plays a direct role in triggering a signal cascade that leads to cytokine production or whether it is required simply to release other bacterial product(s) into the host cell cytosol. Interestingly, mouse strains that displayed a rapid CD8 + T cell IFN-γ response (C57BL/6, 129, and NZB) all had lower bacterial burdens in the liver 3 days postinfection compared with mouse strains that did not have an early CD8 + T cell IFN-γ response (BALB/c, A/J, and SJL). These data suggest that participation of memory CD8 + T cells in the early immune response against L. monocytogenes correlates with innate host resistance to infection.
Systems whose distributed simulation requires low overhead

The author identifies a class of systems which can be simulated by distributed simulation with low overhead. Many cyclic systems are included in this class. He shows that this class of systems has special properties allowing him to develop schemes specifically tailored for it with lower overhead than a direct application of general-purpose schemes in previous studies. The author shows that in simulating these systems, the scheme in a particular study would have lower overhead than its usual overhead in simulating more general systems. >
Disease-Associated Human Telomerase RNA Variants Show Loss of Function for Telomere Synthesis without Dominant-Negative Interference

Telomerase adds simple-sequence repeats to chromosome ends to offset the terminal sequence loss inherent in each cycle of genome replication. Inherited mutations in genes encoding subunits of the human telomerase holoenzyme give rise to disease phenotypes including hematopoietic failure and pulmonary fibrosis. Disease-associated variants of the human telomerase RNA are expressed in heterozygous combination with wild-type telomerase RNA. Here, we exploit a sensitized human primary cell assay system to investigate the biological function of disease-linked telomerase RNA variants and their impact on the function of coexpressed wild-type telomerase RNA. We find that telomerase RNA variants discovered in patients with dyskeratosis congenita or aplastic anemia show loss of function without any indication of dominant-negative impact on telomere maintenance by the coexpressed wild-type RNA. To reconcile this result with contradictory findings from reconstitution assays in vitro, we demonstrate that the lack of dominant-negative impact on telomere maintenance correlates with physiological assembly of active human telomerase holoenzyme ribonucleoproteins harboring monomers rather than higher-order multimers of telomerase RNA and telomerase reverse transcriptase. These findings support loss of function of telomerase RNA as a general mechanism of human disease.
Minium parvum gen. et sp. nov., a crustose member of the Rhodymeniales (Rhodophyta)

Abstract Minium parvum gen. et sp. nov. exists in all stages as a crust, a growth form previously unknown in the order to which it belongs-the Rhodymeniales. While members of this order exhibit a diversity of thallus form and anatomy, only erect or decumbent types have been described heretofore. The new crustose genus comprises plants which grow epiphytically on subtidal articulated coralline algae. The vegetative crust is extremely thin, consisting of a basal layer one cell thick which bears assurgent filaments one to several cells in length. Gametophytes and tetra-sporophytes are isomorphic. In culture they alternate with one another. Reproductive structures are produced in nemathecia which arise from limited areas of the crust and which often expand laterally over the surface. Cruciately divided tetrasporangia are borne terminally among sterile filaments. Carposporangia develop in dense lobes and no tela arachnoidea is formed. While Minium unquestionably belongs to the Rhodymeniales, its position withi...
Cross-Cultural Evaluation of Item Wording Effects on an Attitudinal Scale:

Previous studies have shown that method effects associated with item wording produce artifactual factors and threaten scale validity. This study examines item wording effects on a scale of attitude...
Nucleolus organizer regions in diploid and heteroploid chinese hamster cell lines.

Active nucleolus-organizer regions (NOR) were identified on chromosomes 3, 4, 5, 7, 8, and 9 in a diploid Chinese hamster primary strain (CHFP-WG). However, they appeared only on one chromosome 4, both chromosomes 5, and the isochromosome for the short arm of chromosome 8 (iso 8p) in an established Chinese hamster line displaying gross chromosomal rearrangements (AK412). Some recognizable NOR sites, exhibiting active NOR in CHFP-WG cells fail to exhibit active NOR in AK412, suggesting that a specific suppression of NOR has occurred in the AK412 cells.
The role of lipoprotein(a) in clotting reactions during lipoprotein apheresis—A case report

In individuals with familial hypercholesterolemia (FH) who are unable to reach a target low-density lipoprotein level on a drug regimen, lipoprotein apheresis (LA) may be the treatment of choice. Severe reactions involving clotting during LA are not well described in the literature. We report a case of a 63-year-old woman with FH and markedly elevated lipoprotein(a) (Lp[a]) levels who experienced such a reaction while undergoing LA with a dextran-sulfate cellulose column on the Kaneka MA-01 Liposorber system. Owing to the clotting as well as a blood pressure drop to <100 mm Hg systolic, the procedure was stopped early. Before her second procedure, she was given an increased loading dose of unfractionated heparin. She did not develop clotting during this second procedure. A growing body of literature on the role of Lp(a) in atherothrombotic complications and hemostasis supports a possible mechanism by which clotting in the instrument could occur during apheresis. Our patient's initial pretreatment Lp(a) was 3.5 times greater than the mean Lp(a) levels in patients with FH. This theory is consistent with our case in that the patient's Lp(a) levels progressively declined with each procedure, and she had no subsequent clotting.
Haze Particle Nucleation Simulations in Cirrus Clouds, and Applications for Numerical and Lidar Studies

Abstract A one-dimensional cloud microphysical model is applied to exploring the basic conditions under which ice crystal nucleation, from the homogeneous freezing of ammonium sulfate haze particles, can occur in cirrus clouds at temperatures ≲ −35°C. Cirrus generating regions maintained by uniform updrafts of 0.1–0.25 m s−1, and an idealized ice crystal precipitation mechanism dependent on vertical wind shear are treated in the model. The findings indicate that ice crystals are generated in a pulse-like fashion as a result of water vapor competition effects from ice crystals nucleated within an updraft, followed by precipitation. Water saturation is not required for ice crystal nucleation at ≲ −35°C, and the relative humidities required at decreasing temperatures gradually decrease. The temperature dependency of the relative humidities associated with ice production does not depend significantly on model inputs, suggesting that cirrus cloud processes follow an adjusted pseudoadiabat, which produces ice m...
Mitos y realidades sobre dinámica de la pobreza. Fundamentos de protección social para países en desarrollo

"Este trabajo presenta una sintesis de fundamentos conceptuales para disenar sistemas de proteccion social en paises en desarrollo. Los fundamentos discutidos rinen con creencias comunes, por lo que se presentan en forma de mitos y realidades. Los mitos son: i) La volatilidad del ingreso del hogar es el problema, ii) Los choques macroeconomicos son la principal fuente de riesgo para los hogares, iii) Hogares sin acceso a servicios sociales ni bancarios estan desprotegidos, iv) La proteccion social debe organizarse por riesgos, v) Con estadisticas de corte transversal podemos informar apropiadamente politicas publicas para intervenir la dinamica de la pobreza."
Communication Practices and Advice in Later-Life Widowhood: “We Just Talked about What It Is like to Not Have Your Buddy”

The present study addressed the question of how interactions with social networks influence the experience of widowhood for later-life widowed individuals, and what aspects of these experiences the participants wish others could know. I interviewed 23 widowed individuals. Four themes emerged revolving around the need to prepare for death through communication, the importance of supportive interactions, the value of remembering and sharing the good times, and the significance of finding a balance with grief and maintaining an active life.