cssi/SciSciGPT-SciSciNet huggingface dataset:
N-methyl-D-aspartate receptor-mediated changes in thermal nociception: allosteric modulation at glycine and polyamine recognition sites

The effects of allosteric modulators of the N-methyl-D-aspartic acid receptor ion-channel complex on the nociceptive tail-flick reflex were studied in awake rats. Intrathecal administration of D-serine (100 fmol-1 mumol) but not L-serine or glycine to the lumbar spinal cord produced a facilitation of the tail-flick reflex at doses > or = 1 pmol (maximum at 0.5-1 min). Intrathecal pretreatment with the glycine modulatory site antagonist 7-chlorokynurenic acid (3 pmol) blocked both D-serine-produced and N-methyl-D-aspartate-produced facilitation of the tail-flick reflex. D-serine-produced facilitation was also blocked by intrathecal pretreatment with a N-methyl-D-aspartate receptor ion-channel blocker, MK 801 (100 fmol), or with an alternate substrate for nitric oxide synthase, NG-nitro-L-arginine-methyl ester (100 nmol). Intrathecal administration of spermine (0.01 nmol-3 mumol) produced biphasic effects on tail-flick latency accompanied by mechanical hyperesthesia and vocalization at greater doses. Spermine-produced facilitation (maximum with 0.01 nmol to 1 nmol at 1 min) was blocked by intrathecal pretreatment with MK 801 (100 fmol), NG-nitro-L-arginine-methyl ester (100 nmol) or the polyamine modulatory site antagonist, arcaine (10 nmol). Spermine-produced inhibition (maximum with 300 nmol at 2 min) was blocked by intrathecal administration of MK 801 (1 nmol). Intrathecal administration of the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonopentanoic acid (1 nmol), blocked inhibition and uncovered a facilitation produced by 1 mumol spermine. In addition, spermine produced multi-stage motor effects (immediate- and late-onset). Intrathecal pretreatment with MK 801 (1 nmol) blocked only the immediate-onset motor effects while the late-onset motor effects were selectively blocked by pretreatment with the kappa opioid receptor antagonist, nor-binaltorphamine (200 nmol). Taken together, these data suggest that D-serine and spermine facilitate nociceptive transmission by positive allosteric modulation of the N-methyl-D-aspartate receptor ion-channel. Furthermore, activation of the N-methyl-D-aspartate receptor is also necessary to elicit the immediate-onset motor effects and inhibition of the tail-flick reflex produced by greater doses of spermine. Because kappa opioid receptors appear to be involved, the spermine-produced late-onset motor effects may involve endogenous dynorphin release.
Radioligand Exchange Binding Cannot Directly Determine the Dissociation Constant (Kd) of the Rat Ventral Prostate Nuclear Androgen Receptor: Valid Kd Determinations Require Additional Uptake Binding Data

Radioligand exchange was examined for its ability to derive the dissociation constant (Kd) of the rat ventral prostate nuclear androgen receptor. In one 24-h, 12°C incubation, Scatchard plot analysis of [3H]dihydro-testosterone ([3H]DHT) exchange binding produced a Kd of 6.9 × 10−9 M. Specific binding of [3H]DHT ranged from 114 to 758 pM, and the extrapolated value for the total number of binding sites (n) was 1320 pM. When aliquots from the same receptor pool were incubated with unlabeled DHT, and bound androgen was measured by radioimmunoassay, each titration point held a concentration of specifically bound unlabeled DHT little different from the preincubation value of bound endogenous ligand (1338 pM), suggesting that few, if any, unoccupied sites were created during the incubation. In a second radioligand exchange assay, unoccupied receptor sites were measured at the end of incubation. Virtually no unoccupied sites were found, though the range of predicted values was 124 to 383 pM (n = 425 pM). The data, in toto, suggest that although radioactive ligand exchanges with bound unlabeled ligand, the dynamics of the process do not include the creation of unoccupied sites. Since the Kd is determined by measuring the concentrations of unoccupied sites, free ligand, and receptor sites bound to ligand, the absence of unoccupied sites suggests that radioligand exchange cannot be used to directly determine the Kd of the prostate nuclear androgen receptor. The numerical value obtained from radioligand exchange, therefore, instead of being a Kd, is very likely the result of a graphic plot of the increase in specific activity of bound radioligand as [3H]DHT is titrated to higher levels. In the last phase of the study a technique was developed which allows for the correct determination of the Kd of the rat ventral prostate nuclear androgen receptor. For the determination, data from an experiment measuring uptake binding into unoccupied sites were combined with data obtained from radioligand exchange binding. From this, the Kd of the receptor was calculated to be 1 × 10−12 M.
Regulation and function of Dbx genes in the zebrafish spinal cord

Dbx homeodomain proteins are important for spinal cord dorsal/ventral patterning and the production of multiple spinal cord cell types. We have examined the regulation and function of Dbx genes in the zebrafish. We report that Hedgehog signaling is not required for the induction or maintenance of these genes; in the absence of Hedgehog signaling, dbx1a/1b/2 are expanded ventrally with concomitant increases in postmitotic neurons that differentiate from this domain. Also, we find that retinoic acid signaling is not required for the induction of Dbx expression. Furthermore, we are the first to report that knockdown of Dbx1 function causes a dorsal expansion of nkx6.2, which is thought to be the cross-repressive partner of Dbx1 in mouse. Our data confirm that the dbx1a/1b/2 domain in zebrafish spinal cord development behaves similarly to amniotes, while extending knowledge of Dbx1 function in spinal cord patterning.
Hydrophobic oxime ethers: a versatile class of pDNA and siRNA transfection lipids.

The manipulation of cationic lipid structure to increase polynucleotide binding and delivery properties while also minimizing associated cytotoxicity has been a principal strategy for developing next-generation transfection agents. The polar (DNA-binding) and hydrophobic domains of transfection lipids have been extensively studied; however, the linking domain comprising the substructure used to tether the polar and hydrophobic domains has attracted considerably less attention as an optimization variable. Here, we examine the use of an oxime ether as the linking domain. Hydrophobic oxime ethers were readily assembled via click chemistry by oximation of hydrophobic aldehydes using an aminooxy salt. The facile ligation reaction delivered the title compounds with hydrophobic domain asymmetry. Using the MCF-7 breast cancer, H1792 lung cancer and PAR C10 salivary epithelial cell lines, our findings show that lipoplexes derived from the oxime ether lipids transfect in the presence of serum at higher levels than commonly used liposome formulations, based on both luciferase and GFP assays. Given the biological compatibility of oxime ethers and their ease of formation, this functional group should find much application as a linking domain in future designs of transfection vectors.
Phase behavior and dynamics of fluids in mesoporous glasses

Equilibrium and dynamical relaxation behavior of fluids confined in disordered mesoporous glasses such as Vycor are studied based on a lattice model using mean field theory and Monte Carlo simulations. Preferential attractive interactions between the solid surfaces and the fluid suppresses macroscopic phase separation, while making the relaxation rate increasingly slow. The free energy landscape characterized by the presence of the many metastable minima separated by finite barriers dominates both the static and dynamic behavior of fluids at low temperature. Our results provide additional insight into the nature of hysteresis in adsorption measurements of gases in porous glasses.
Transforming massive data to pragmatic target marketing practice

Marketing is all about the process of communicating the value of a product or service to customers in order to stimulate sales, while target marketing maximizes the return on investment into the marketing activities. We present a piece of practice to transform massive data into actionable insights and guidance using statistical analysis and data mining methods, which helps a leading home appliance manufacturer optimize its marketing strategy for increasing customer intimacy, solidifying customer loyalty, and most importantly, boosting the sales volume and profit.
Hemodialysis as a treatment for schizophrenia

Abstract The author reviews available reports on the effects of renal dialysis on schizophrenia and offers critiques of these studies and their conclusions. He also addresses the possible mechanisms of action for hemodialysis on the psychoses, along with the risks inherent in dialysis research.
The free amino acids in Trichomonas foetus.

Abstract The free amino acid content of protoplasmic extracts of Trichomonas foetus was determined by unidimensional polychromatic and two-dimensional paper chromatography to include cystine-cysteine, aspartic acid, glycine, serine, glutamic acid, threonine, alanine, tyrosine, leucine-isoleucine, ornithine, lysine, arginine, valine, methionine, proline, phenylalanine, and possibly histidine. In addition, analyses by similar methods were made of ingredients of the medium on which the trichomonads were cultured, in an attempt to determine the direct source of those free amino acids present in T. foetus . With the exception of β-alanine, all amino acids identified in the medium were found in T. foetus extracts.
A Decade of Rare Donor Services in the United States

Between 1981 and 1990, the American Red Cross Rare Donor Registry supplied 9,872 units of red cell components with rare phenotypes to blood centers in the United States and abroad. Approximately 51% were from donors with high-frequency antigen-negative phenotypes and 49% were from donors with multiple antigen-negative phenotypes. Since 1989, the disease category requiring the largest number of units has been sickle cell disease. Strategies to ensure that the Registry will have adequate resources to meet future requirements include testing selected donors for rare phenotypes and blood conservation programs, such as intraoperative salvage and the treatment of anemia of chronic renal failure with recombinant erythropoietin.
Numerical analysis of flow in an elastic artery model.

Oscillatory and pulsatile flows of Newtonian fluids in straight elastic tubes are simulated numerically with the aid of Ling and Atabek's "local flow" assumption for the nonlinear convective acceleration terms. For the first time, a theoretical assessment of the local flow assumption is presented, and the range of validity of the assumption is estimated by comparison with perturbation solutions of the complete flow problem. Subsequent simulations with the local flow model indicate that the flow field and associated wall shear stress are extremely sensitive to the phase angle between oscillatory pressure and flow waves (impedance phase angle). This phase angle, which is a measure of the wave reflection present in the system, is known to be altered by arterial disease (e.g., hypertension) and vasoactive drugs. Thus, the paper elucidates a mechanism by which subtle changes in systemic hemodynamics (i.e., phase angles) can markedly influence local wall shear stress values.
Influence of membrane support structure on the efficiency of an iron-modified silica nanofiltration membrane

Inorganic membranes are generally created by depositing a thin film separation (membrane) layer atop a supporting structure in order to provide for the physical durability of the membrane. The separation layer thickness and morphology are normally evaluated to determine their contribution to fluid flow resistance across the membrane. The supporting structure is often ignored, yet can affect the quality of the membrane formed and significantly influence the global efficiency of the membrane module. In this paper, three different support structures are compared and evaluated with respect to the efficiency (rejection and flux) of an iron-modified silica separation layer. The main difference in the supports was the nominal pore size of the surface responsible for facilitating the membrane layer. The pore sizes of the supports investigated were 5, 10, and 20 nm in diameter. It was hypothesized that the largest pore size support would produce a higher water flux. However, this support did not provide an adequate surface for the deposition of a high quality membrane layer. The formation of an intact membrane layer was successfully achieved using the other two support structures. From the results obtained from salt rejection and flux data of these two functional membrane modules, the influence of the support structure on the overall efficiency of the membrane module was assessed. The 10 nm support structure produced a water flux that was 1.6 times greater than that of the 5 nm pore size support, without sacrificing the rejection of the electrolytes studied.
Multichannel variational expressions of scattering theory.

We have compared variational functionals for multichannel scattering. The functionals considered were Schwinger-type functionals based on the close-coupling equations, the Schwinger-type variational functionals of Takatsuka and McKoy (Phys. Rev. A 24, 2473 (1981)), and a Kohn-type variational functional. The results for a simple Huck-model potential containing both open and closed channels indicate that the Schwinger-type variational functionals yielded very similar results and that all the methods considered converged at a similar rate with respect to the closed-channel expansion. To obtain good convergence with any of these methods it was essential to include separate trial functions outside the range of the Huck square-well potential in the channels where a correct asymptotic form of the wave function was required, those being only the closed channels for the Schwinger-type functionals and both open and closed channels for the Kohn-type functionals. These asymptotic functions were needed to reproduce the discontinuity in the second derivative of the wave function due to the discontinuities in the model potential. Convergence characteristics of these methods with respect to target-state expansions were also considered.
The tradeoffs of societal computing

As Social Computing has increasingly captivated the general public, it has become a popular research area for computer scientists. Social Computing research focuses on online social behavior and using artifacts derived from it for providing recommendations and other useful community knowledge. Unfortunately, some of that behavior and knowledge incur societal costs, particularly with regards to Privacy, which is viewed quite differently by different populations as well as regulated differently in different locales. But clever technical solutions to those challenges may impose additional societal costs, e.g., by consuming substantial resources at odds with Green Computing, another major area of societal concern. We propose a new crosscutting research area, Societal Computing, that focuses on the technical tradeoffs among computational models and application domains that raise significant societal issues. We highlight some of the relevant research topics and open problems that we foresee in Societal Computing. We feel that these topics, and Societal Computing in general, need to gain prominence as they will provide useful avenues of research leading to increasing benefits for society as a whole.
Radiology health services research: from imperative to legislative mandate.

OBJECTIVE. In the era of health care reform, our value-added to patient care, its corresponding level of reimbursement, and the stature of radiology as a specialty will likely be grounded in the scientific evaluation methods of health services research.CONCLUSION. We need to create more opportunities for training, provide resources and incentives for the brightest candidates to enter this field, and cultivate enriching environments for health services research in all academic radiology departments.
On the mechanism of intragenic recombination. II. Neurospora crassa.

Abstract A mechanically simple model of intragenic recombination is described. In the first paper of this set the quantitative expectations of this model were compared with data from phage T4. Here, the model is discussed with respect to the extensive intragenic recombination data available from Neurospora crassa. The following aspects are considered: (a) linearity; (b) additivity; (c) non-reciprocity; (d) high negative interference; (e) the conservativeness of the chromosome replications associated with meiosis; (f) evidence bearing on whether intragenic and intergenic recombination occur by separate mechanisms; (g) chromatid interference; and (h) segregations occurring at divisions subsequent to meiosis. An appendix is included which gives the predictions of the model with respect to three standard types of genetic analysis.
The role of mechanisms, integration, and unification in science and psychology

I assume the importance of unifying theories in science but suggest that psychologists do not understand the concept. To clarify, I distinguish unification from both mechanisms and from integration...
Defence spending and economic growth

In this paper the connection between defence spending and economic growth is investigated. The econometric approach is based on a two sector production function model of the economy. In light of the plausibility of significant cuts in defence spending during the forthcoming years, a quantitative analysis is made assessing the effects of defence spending cuts. The results reveal that there is a positive and significant relation between defence spending and economic growth. But, findings also indicate that the responsiveness of economic growth to changes in defence spending is small. If there are significant cuts in defence spending—except for very large sustained cuts—the adverse effects on the economic growth of the United States should not be large.
Lifetime of microsomal cytochrome P-450 and steroidogenic enzymes in rat testis as influenced by human chorionic gonadotrophin

The lifetime of different microsomal steroidogenic enzymes and the cytochrome components of the NADPH-cytochrome P-450 pathway have been determined in rat testis by measuring their decrease logarithmically after hypophysectomy. Although both cytochrome P-450 and 17α-hydroxylase show biphasic decay curves, the first decay curve contains 89–94% of the cytochrome P-450 and 17α-hydroxylase levels. Steroidogenic enzymes which are located mainly in the leydig cells, decay much faster than microsomal protein, t12 = 12 days, which represents mainly decay of tubular protein. The similarity between the major half-life of cytochrome P-450, t12 = 3.3 days, 17α-hydroxylase, t12 = 2.3 days and the C17–C20 lyase, t12 = 3.4 days and the uniformity of their response to human chorionic gonadotrophin (HCG) provides additional evidence that these two steroidogenic enzymes require cytochrome P-450. Both the 17α-hydroxylase and the C17–C20 lyase were shown to have a constant activity per nmole of cytochrome P-450 during a sixfold change in the level of cytochrome P-450 brought about by HCG treatment of rats with intact pituitaries. The decay of 17β-hydroxysteroid dehydrogenase, t12 = 4.5 days, was slower than P-450 dependent enzymes. Rats with intact pituitaries are not under maximal stimulation by endogenous LH because addition of HCG increases the levels of microsomal and mitochondrial cytochrome P-450 220 and 1620%, respectively. The rates of synthesis during the increase from one cytochrome P-450 level to another was calculated at 0.1182 testes/day for microsomal cytochrome P-450 and 0.10 nmoles/2 testes/day for mitochondrial cytochrome P-450. Treatment of hypophysectomized rats with HCG results in large increases of cytochrome P-450, 17α-hydroxylase, C17–C20 lyase and 5α-reductase, but not cytochrome b5, microsomal protein, 7α-hydroxylase, or the 17β-hydroxysteroid dehydrogenase. While it is clear that the two cytochrome P-450 dependent hydroxylases involved in steroidogenesis and the 5α-reductase are under the control of gonadotrophin, it is not clear how 17β-hydroxysteroid dehydrogenase levels are maintained or in what manner the 5α-reductase level is controlled in mature animals.
EVIDENCE FOR QUANTIZED VORTICES IN A SUPERCONDUCTING STRIP

Results of a study of the properties of extremely narrow superconducting film strips in a perpendicular magnetic field are reported. Resistivity vs magnetic field curves obtained in the intermediate state at the transition temperature indicate that quantized current vortices are present, and that in the limit of very narrow strips, their size depends upon the width of the strip. (C.E.S.)
Rapid Filamentation Zone in a Numerically Simulated Tropical Cyclone

Abstract In a recent study, Rozoff et al. proposed a possible mechanism to explain the formation and maintenance of the weak-echo annulus (or moat) outside of the primary eyewall of a tropical cyclone observed in radar images. By this mechanism, the moat is determined to be a region of the strain-dominated flow outside of the radius of maximum wind in which essentially all fields are filamented and deep convection is hypothesized to be highly distorted and even suppressed. This strain-dominated region is defined as the rapid filamentation zone wherein the filamentation time is shorter than the overturning time of deep convection. An attempt has been made in this study to test the hypothesis in a full-physics tropical cyclone model under idealized conditions and to extend the concept to the study of the inner-core dynamics of tropical cyclones. The foci of this paper are the evolution of the rapid filamentation zone during the storm intensification, the potential roles of rapid filamentation in the organiz...
History of neuroaugmentative procedures

Neuroaugmentation, the use of chronic stimulation of the brain and spinal cord for pain management, developed during the past 30 years. It evolved, however, from concepts of pain treatment that were based on observations and clinical experience dating back an additional two decades or more. The appreciation of the role of the extralemniscal system and descending influences from the brain in modulation of pain perception led to the Melzack-Wall gate theory. The concept proposed in that theory, that pain perception could be lessened by increasing activity in neural structures not associated with pain, led to chronic stimulation of deep brain and spinal cord as a modality for the management of chronic pain. Both brain and spinal structures emerged as targets for neuroaugmentation.
Interfacial Mixing in Epitaxial Co/Pt Superlattices: a Source of Magnetocrystalline Anisotropy

We report the results of photoelectron forward scattering studies of Co-Pt interfaces during the growth of epitaxial superlattices by MBE. These studies reveal that the interfaces are not atomically abrupt but exhibit limited interdiffusion. The dependence of magnetic anisotropy on growth axis and the strong 2-fold in-plane anisotropy for [110] oriented superlattices suggests that magnetocrystalline anisotropy is a major factor in determining the anisotropy in Co/Pt superlatticcs. The possibility that this anisotropy may arise from a combination of structural defects and local ordering is discussed.
Increased testosterone in type I diabetic subjects with severe retinopathy.

Abstract Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured serum testosterone, estradiol, DHEA-S, and sex hormone binding globulin levels in 26 men and 22 women with type I diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a populationbased study of diabetic complications. The mean age was 23 years and the mean duration of diabetes was 14 years. Subjects with proliferative or preproliferative retinopathy (≥ retinopathy level 51-80) were matched by duration of diabetes (±2 years) and sex to subjects with minimal or no retinopathy (≥ retinopathy level 21). Seven stereoscopic retinal photographs of each eye were obtained and photographs were read by the University of Wisconsin Reading Center. Serum testosterone concentrations were significantly higher in male diabetic subjects with proliferative retinopathy (648 ± 36 ng/dl) than in male diabetic subjects with minimal or no retinopathy (512 ± 43 ng/dl) ( P = 0.017). No other statistically significant differences in sex hormones between subjects with and without proliferative retinopathy were observed. Although these results should be regarded as preliminary because of the small number of subjects, they support the hypothesis that testosterone concentrations may be associated with the development of retinopathy in type I diabetic patients.
Amplification of the biotin-avidin immunofluorescence technique

An amplification of the immunofluorescence technique which uses biotinylated antibody and fluoresceinated avidin is described. By introducing a sandwich technique using fluorescein-conjugated goat anti-avidin, a 5-fold enhancement of staining over the conventional immunofluorescence method is achieved, and the brightness is more than twice that achieved with the simple biotin-fluoresceinated avidin reaction.
On the control of linear systems whose coefficients are functions of parameters

The stabilization and regulation of linear discrete-time systems whose coefficients depend on one or more parameters is studied. For linear systems whose coefficients are continuous functions of real or complex parameters (respectively, analytic or rational functions of real parameters), it is shown that reachability of the system for all values of the parameters implies that the system can be stabilized using gains that are also continuous (analytic, rational) functions of the parameters. Closed-form expressions for a collection of stabilizing gains are given in terms of the reachability Gramian. For systems which are stabilizable for all values of the parameters, it is shown that continuous (analytic, rational) stabilizing gains can be computed from a finite-time solution to a Riccati difference equation whose coefficients are functions of the parameters. These results are then applied to the problem of tracking and disturbance rejection in the case when both the plant and the exogenous signals contain parameters.
Palladium-catalyzed synthesis of fused indoles

Abstract A novel route to fused indoles via two consecutive palladium catalyzed reactions, an intramolecular Heck reaction followed by a reductive N-heteroannulation, has been developed. For example, reaction of 2-bromo-3-nitro-1-(3-butenyloxy)benzene with palladium diacetate, and tri(o-tolyl)phosphine in the presence of triethylamine gave a readily separable mixture (18:4:1) of dihydro-4-methylene-5-nitro-2H-1-benzopyran, 4-methyl-5-nitro-2H-1-benzopyran, and 4-methyl-5-nitro-4H-1-benzopyran. Reaction of pure dihydro-4-methylene-5-nitro-2H-1-benzopyran with palladium diacetate, 1,3-bis(diphenylphosphino)propane, and carbon monoxide in DMF (120 °C, 70 h, 60 psi CO) gave 3,5-dihydro-2H-pyrano[4,3,2-cd]indole in 63% yield.
Application of the NT Solvent Nucleophilicity Scale to Attack at Sulfur: Solvolyses of Benzenesulfonyl Chlorides

The specific rates of solvolysis of benzenesulfonyl chloride and three 4-substituted derivatives can be very well correlated using the extended Grunwald-Winstein equation, with incorporation of NT solvent nucleophilicity and YCl solvent ionizing power values. In two instances, it was shown that almost identical correlations were obtained after the incorporation of methyl groups into the 2- and 6-positions of the benzene ring. No evidence was found for a dissociative (SN1) mechanism or for a duality of mechanism. All of the results can be rationalized in terms of a concerted bimolecular displacement (SN2) mechanism, involving attack by solvent at sulfur.
Dermatoses among housekeeping personnel.

Abstract Background: Housekeepers are exposed to irritants and allergens in their work and are at significant risk for developing occupationally induced contact dermatitis. Objective: We studied housekeepers at the Hershey Medical Center to determine the cause and frequency of contact dermatitis and contact urticaria in these workers. Methods: All housekeepers were examined. Those with hand dermatitis had an extensive history, patch testing, and latex RAST testing. Results: Eight of 130 had hand dermatitis. None had a relevant positive patch test or positive RAST test. Conclusions: Of our housekeepers, 6.2% had occupationally induced irritant contact dermatitis. None had allergic contact dermatitis or contact urticaria to latex.
Selectively enriched [γ-13C]-histidine as a nuclear magnetic resonance probe of enzyme structure and function. Synthesis and incorporation into E.coli alkaline phosphatase

Summary The 13 C nmr spectrum of E. coli alkaline phosphatase in which the γ positions of the histidine residues are enriched in 13 C is reported. The labelled enzyme samples were prepared by in vivo incorporation of [γ- 13 C]-histidine, or [γ- 13 C]-β,β-dideuteriohistidine. Eight clearly resolved 13 C nmr signals were observed, corresponding to the eight or nine histidine residues per subunit. The observed narrow linewidths and sensitivity to environment of histidine C γ resonances in alkaline phosphatase suggest that 13 C enrichment at this quaternary carbon position will prove useful in determining details of enzyme structure and mechanism by means of 13 C nmr measurements.
Long‐term weight control study II (weeks 34 to 104)

Between weeks 34 and 104, we explored different schema for administering fenfluramine plus phentermine in open-label fashion. At week 34, the original placebo group participants began taking fenfluramine plus phentermine (placebo-to-active group). Those receiving fenfluramine plus phentermine between weeks 6 and 34 either continued to receive medication or began targeted intermittent therapy. Participants who did not lose 10% of initial weight received an augmented dose (60 mg fenfluramine plus 30 mg phentermine. The placebo-to-active group lost an additional 9.1 +/- 0.8 kg (mean +/- SEM) in the period from week 34 to week 60. At week 60, they were assigned to either continue medication, intermittent therapy, or augmented therapy. More than 68% (83) of the original participants completed up to study week 104. At that point, overall weight loss was 10.8 +/- 0.7 kg (11.6 +/- 0.8% of initial weight); participants who continued to receive fenfluramine plus phentermine lost 11.6 +/- 0.8 kg, participants receiving intermittent therapy lost 11.6 +/- 1.3 kg, and participants receiving augmented therapy lost 6.5 +/- 1.5 kg. Although 41% of the participants complained of dry mouth, neither serious adverse effects nor evidence of medication abuse appeared. There were 29 dropouts in the period from weeks 34 to 104. Sixteen of those were related to medication (adverse effects, lack of efficacy, and fear of medication). Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise continued to be efficacious for up to 2 years.
Heterotrophic microbial activities and nutritional status of microbial communities in tropical marsh sediments of different salinities: the effects of phosphorus addition and plant species

Oligotrophic, phosphorus (P) limited herbaceous wetlands of northern Belize are being impacted by P loading from fertilizer runoff. P enrichment causes a shift in autotroph communities from a microphyte (cyanobacterial mats, CBM) to macrophyte (Eleocharis spp., Typha domingensis) dominated system. To document potential effects of P, salinity, and macrophyte species on the heterotrophic microbial community nutritional status (represented especially by specific phospholipids fatty acids and specific respiration rate), biomass and activities, we took soil samples from established P enrichment plots in replicated marshes of two salinity levels. P addition increased microbial biomass carbon (C), nitrogen (N) and P, as well as soil nutrient transformation rates (nitrogenase activity, N mineralization and immobilization, methanogenesis). The effect of plant species (Eleocharis vs Typha sites) was generally lower than the effect of P addition (CBM vs Eleocharis sites) and was most evident at the low salinity sites, where Eleocharis dominated plots had enhanced nitrogenase activity and P microbial immobilization. Salinity reduced the overall rates of microbial processes; it also weakened the positive effect of both P addition and plant species on microbial activities. Lastly, the amount of N stored in microbial cells, likely in form of osmoprotective compounds, was enhanced by salinity.
Implementing a high-performance multithreaded microprocessor: a case study in high-level design and validation

We have developed a 16-way multithreaded microprocessor called BlueSPARC. This in-order, high-throughput processor incorporates complex features such as privileged operations, memory management, and a non-blocking cache subsystem. When supported by a hybrid simulation technique that handles rare, unimplemented behaviors in a software host, the BlueSPARC microprocessor runs unmodified UltraSPARC III-based commercial applications on Solaris 8 while hosted on a single Xilinx XCV2P70 FPGA clocked at 90MHz. This significant effort was achieved in under one man-year using a high-level language and a high-level validation approach. In the first part of the paper, we describe our experience in applying the Bluespec SystemVerilog (BSV) language to develop a large hardware design that must meet specific area and performance requirements. In the second part of the paper, we present the FPGA-accelerated validation approach we employed to check the correct execution of real multithreaded programs running on the BlueSPARC processor. We discuss the challenges and our solutions to validation in the presence of full-system interactions and microarchitectural nondeterminism.
Sodium Intake and Blood Pressure Among US Children and Adolescents

associated with early development of cardiovascular disease and risk for premature death. High sodium intake and overweight/ obesity are recognized as risk factors for hypertension in children. WHAT THIS STUDY ADDS: These results show that usual sodium intake was positively associated with systolic blood pressure and risk for pre-high blood pressure and high blood pressure among US children. The data indicate a synergistic interaction between sodium intake and weight status on risk for high blood pressure. abstract To assess the association between usual dietary sodium intake and blood pressure among US children and adolescents, over- all and by weight status. METHODS: Children and adolescents aged 8 to 18 years (n = 6235) who participated in NHANES 2003-2008 comprised the sample. Subjects' usual sodium intake was estimated by using multiple 24-hour dietary recalls. Linear or logistic regression was used to examine association between sodium intake and blood pressure or risk for pre-high blood pressure and high blood pressure (pre-HBP/HPB). RESULTS: Study subjects consumed an average of 3387 mg/day of sodium, and 37% were overweight/obese. Each 1000 mg per day sodium intake was associated with an increased SD score of 0.097 (95% confidence interval (CI) 0.006-0.188, ∼1.0 mmHg) in systolic blood pressure (SBP) among all subjects and 0.141 (95% CI: -0.010 to 0.298, ∼1.5 mm Hg) increase among overweight/obese subjects. Mean adjusted SBP increased progressively with sodium intake quartile, from 106.2 mm Hg (95% CI: 105.1-107.3) to 108.8 mm Hg (95% CI: 107.5-110.1) overall (P = .010) and from 109.0 mm Hg (95% CI: 107.2-110.8) to 112.8 mm Hg (95% CI: 110.7-114.9; P = .037) among those overweight/obese. Adjusted odds ratios comparing risk for pre-HBP/HPB among subjects in the highest versus lowest sodium intake quartile were 2.0 (95% CI: 0.95-4.1, P = .062) overall and 3.5 (95% CI: 1.3-9.2, P = .013) among those overweight/obese. Sodium intake and weight status appeared to have synergistic effects on risk for pre-HBP/HPB (relative excess risk for interaction = 0.29 (95% CI: 0.01-0.90, P , .05). CONCLUSIONS: Sodium intake is positively associated with SBP and risk for pre-HBP/HPB among US children and adolescents, and this as- sociation may be stronger among those who are overweight/obese. Pediatrics 2012;130:611-619
The Impact of State Capacity on Enforcement of Environmental Policies: The Case of China

Does variation in state capacity predict compliance with government policies? This article tests the usefulness of state capacity as an analytic tool to evaluate environmental policy enforcement in China. The study employs two methodological approaches: first, a quantitative evaluation of capacity among 10 representative Chinese provinces and their compliance with environmental policies dictated by the Chinese central government and second, a qualitative evaluation of the potential causal relationship between state capacity and compliance. The results of these analyses illustrate the central role of state capacity in environmental policy compliance. The results also point to the importance of non-state-capacity factors. The accuracy of analyses relying on the state capacity model is improved if combined with assessments of the policies to be enforced and the commitment of the government responsible for their enforcement.
Monitoring Losses in Menu Items During Foodservice Processing

Methods to monitor losses in menu items are becoming increasingly more important to all foodservice managers. A mathematical model was developed that uses matrices to describe amounts of product losses for a single step or a sequence of steps in foodservice processing. This paper reports a pilot study undertaken to apply the mathematical model to monitor losses of whipped potatoes throughout all stages (heating, mixing, transfer of product and pre-service holding for a 1 hr. period) of food product flow as would occur in a conventional foodservice system. The model was used to estimate losses of water, solids and vitamin C. Losses in the ex perimental product were greatest for the third process step-tranfer of product, and least following pre-service holding. Such a managerial approach would be useful to the foodservice industry in documenting and minimizing losses.
Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke

Lung cancer in lifetime never smokers is distinct from that in smokers, but the role of separate or overlapping carcinogenic pathways has not been explored. We therefore evaluated a comprehensive panel of 11,737 single-nucleotide polymorphisms (SNP) in inflammatory-pathway genes in a discovery phase (451 lung cancer cases, 508 controls from Texas). SNPs that were significant were evaluated in a second external population (303 cases, 311 controls from the Mayo Clinic). An intronic SNP in the ACVR1B gene, rs12809597, was replicated with significance and restricted to those reporting adult exposure to environmental tobacco smoke. Another promising candidate was an SNP in NR4A1, although the replication OR did not achieve statistical significance. ACVR1B belongs to the TGFR-β superfamily, contributing to resolution of inflammation and initiation of airway remodeling. An inflammatory microenvironment (second-hand smoking, asthma, or hay fever) is necessary for risk from these gene variants to be expressed. These findings require further replication, followed by targeted resequencing, and functional validation.
Client Characteristics and the Negotiation Tactics of Auditors: Implications for Financial Reporting

Although the financial statements of an organization are considered a product of management, prior research suggests that a company's financial statements may be affected by the negotiation strategy employed by the auditor when resolving audit differences with management. However, little subsequent research discusses the potential strategies that auditors may employ during the negotiation process. Our study extends the literature by investigating, in a post–Sarbanes-Oxley environment, whether auditors will employ a reciprocity-based strategy for the resolution of audit differences and what client characteristics (client management's negotiating style and client retention risk) increase the extent to which it is utilized. Further, we explore the potential effect of a reciprocity-based strategy on the quality of the financial statements. Such a strategy involves bringing inconsequential items to management and subsequently waiving these items in an effort to encourage management to be more cooperative in the posting of significant income-decreasing adjustments. The results of experiment 1 indicate that client management's negotiating style and retention risk have an interactive effect on auditors' use of a reciprocity-based strategy. Specifically, auditors are more likely to utilize a reciprocity-based strategy when management's negotiating style is competitive and client retention risk is high. Experiment 2 findings suggest that the auditor's use of reciprocity during negotiation can actually result in more conservative financial statements by helping the auditor manage perceived client pressures to waive or reduce proposed adjustments.
Behavioral Geography and the Theoretical/Quantitative Revolution

Beginning with a position statement about the serendipitous nature of the emergence of both normative theory and quantitative methods in Geography, this chapter details the nature of the various contributions to both areas by Behavioral Geographers. Contributions to data collection and both qualitative and quantitative analysis are reviewed for the periods 1960 to the present. Particular emphasis is placed on contributions made by those interested in decision making and choice behavior, particularly in terms of the role of Spatial Cognition (theory and methods) in fostering and extending those dual “revolutions.” Other themes emphasize the development of avenues of publication from the “gray literature” of Department Discussion Papers to the emergence of the journal Geographical Analysis and support by geographers for a variety of interdisciplinary journals. A final focus is on the great variety of themes pursued by the Behavioral Geographer of today, and some suggestions are made regarding possible avenues for future research.
Gross substitutability and the weak axiom of revealed preference

Abstract This paper investigates the relationship between gross substitutability and the weak axiom of revealed preference in excess demand functions. Gross substitutability implies the weak axiom when the number of goods, n , is less than four. There are robust counterexamples to this proposition when n ≧4. Nonetheless, Monte Carlo experiments indicate that violations of the weak axiom are extremely rare in functions that satisfy gross substitutability. They also reveal, however, a new class of demand function that violates the weak axiom. These results are of interest because of the close relationship of the weak axiom to uniqueness of equilibrium in production economies.
The promiscuous protein binding ability of erythrosine B studied by metachromasy (metachromasia)

The present study aims to elucidate aspects of the protein binding ability of erythrosine B (ErB), a poly-iodinated xanthene dye and an FDA-approved food colorant (FD&C Red No. 3), which we have identified recently as a promiscuous inhibitor of protein–protein interactions (PPI) with a remarkably consistent median inhibitory concentration (IC50) in the 5–30 µM range. Because ErB exhibits metachromasy, i.e., color change upon binding to several proteins, we exploited this property to quantify its binding to proteins such as bovine serum albumin (BSA) and CD40L (CD154) and to determine the corresponding binding constants (Kd) and stoichiometry (nb) using spectrophotometric methods. Binding was reversible and the estimated affinities for both protein targets obtained here (Kd values of 14 and 20 µM for BSA and CD40L, respectively) were in good agreement with that expected from the protein–protein interaction (PPI) inhibitory activity of ErB. A stoichiometry greater than one was observed both for CD40L and BSA binding (nb of 5–6 and 8–9 for BSA and CD40L, respectively) indicating the possibility of nonspecific binding of the flat an rigid ErB molecule at multiple sites, which could explain the promiscuous PPI inhibitory activity if some of these overlap with the binding site of the protein partner and interfere with the binding.
The Ecology of the Gym: Reconceptualized and Extended

The ecological paradigm has become a powerful framework for understanding how teachers and students negotiate the learning environment. This article articulates the ecological paradigm into a more cohesive framework and expands it using influential work from the sociology of physical education. First, we explain several core concepts of ecological theory and explain how they fit together. Next, we overview past ecological work in each of the three main task systems, while integrating literature from outside traditional ecological theory to show how it better enhances the paradigm's usefulness. We show how culturally relevant content, student ownership/control, and cooperation/competition provide richness in further explaining the instructional task system. Similarly, we broaden the student social system into a social task system with three dimensions: relationships between teachers and students, relationships among students, and the social climate of the school.
Constraining Nitrogen Inputs to Urban Streams from Leaking Sewers Using Inverse Modeling: Implications for Dissolved Inorganic Nitrogen (DIN) Retention in Urban Environments

Leaking sewer infrastructure contributes nonpoint nitrogen pollution to groundwater and surface water in urban watersheds. However, these inputs are poorly quantified in watershed budgets, potentially underestimating pollutant loadings. In this study, we used inverse methods to constrain dissolved inorganic nitrogen (DIN) inputs from sewage to Nine Mile Run (NMR), an urban watershed (1570 ha) in Pittsburgh, Pennsylvania (USA) characterized by extensive impervious surface cover (38%). Water samples were collected biweekly over two years and intensive sampling was conducted during one summer storm. A nitrogen budget for the NMR watershed was constructed, ultimately inverted, and sewage DIN inputs constrained using Monte Carlo simulation. Results reveal substantial DIN contributions from sewage ranging from 6 to 14 kg ha–1 yr–1. When conservative estimates of DIN from sewage are included in input calculations, DIN retention in NMR is comparable to high rates observed in other suburban/urban nutrient budgets ...