cssi/SciSciGPT-SciSciNet huggingface dataset:
A constitutively active form of CREB can activate expression of the rat prolactin promoter in non-pituitary cells

Abstract The pituitary cell-specific transcription factor Pit-1 has been show to trans-activate expression of the prolactin (PRL) promoter in non-pituitary cells. However, the cyclic AMP response element (CRE)-binding protein CREB is known to play a major role in cell-specific expression of hepatocyte-specific genes. Since the PRL promoter contains an asymmetrical form of a cyclic AMP response element (termed the CLE), we investigated whether CREB could also induce PRL promoter activity in non-pituitary cells. Transient expression in rat glial C6 cells of a constitutively active CREB-VP16 fusion protein strongly trans-activated expression of a co-transfected rat PRL promoter construct, ( −187)PRL-CAT. Analysis by 5'-deletion showed that this response requires PRL promoter sequences between positions −113/ −75. CREB-VP16 did not stimulate expression in C6 cells of any of three control promoter-CAT constructs, implying that the strong response of the PRL promoter to activated CREB is both promoter-specific, and is not due to non-specific transcriptional effects of the potent VP16 moiety of CREB-VP16. Surprisingly, mutations in the CLE only slightly reduced activation by CREB-VP16 of construct (−204)PRL-CAT, implying that the major action of CREB-VP16 on the PRL promoter does not involve a direct interaction with the CLE. CREB-VP16 stimulated PRL-CAT activity in C6 cells as strongly as, and synergistically with, Pit-1. These results imply that CREB can strongly and specifically activate expression of the PRL promoter in non-pituitary cells, via a mechanism different from that employed by Pit-1.
Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer

Abstract Background . Initiation of sun protection strategies can be promoted, to some extent, by educational efforts, but little is known about the merit of continuing education interventions in sustaining the desired behaviors or adding new behaviors. This prospective study clarifies the choices individuals make among the four strategies that allow them to maintain lifestyle changes. Methods . From 1983 to 1987, the population received education about sun protection coupled with the removal of a nonmelanoma skin cancer. One year later, their choice of sun protection methods was determined. Then annually from 1985 to 1989, they received written recommendations about sun protection for a period of 2–6 years after the initial education. The maintenance, cessation, and addition to the initial sun protection behaviors were ascertained by a questionnaire, as was the intention to change. Frequency of physician visits and development of subsequent nonmelanoma skin cancer were evaluated by medical chart review for the 2–6 year phase of continued education. Results . One percent of the population consisting mostly of women described ceasing tanning after 2–6 years of education. The population related a greater use of protective clothing and/or sunscreen with an SPF of 15 or greater as their reported restrictions on outdoor activities ceased. An emerging new strategy of some of the population ( n = 185) was the use of sunscreens with an SPF less than 15 in association with attempts to deliberately tan and longer daily outdoor exposure. Neither frequency of physician visits nor numbers of subsequent nonmelanoma skin cancers influenced continuation or addition of sun protection behaviors. Conclusions . While the greatest reported change in behavior was temporarily associated with educational intervention linked to removal of the skin cancer, continued educational efforts may have recruited some individuals to cease tanning and encouraged others to adopt the use of protective clothing or more frequent sunscreen use as they were unable to maintain the limitations on outdoor activities. It is not possible to structure a control group restricted from mass media education; therefore, the effectiveness of specific behavior-directed education cannot be precisely determined. Nonetheless, the population described using knowledge to develop compensation sun protection strategies that preserved lifestyle.
The Impact of Cost Displays on Ordering

To the Editor: Horn et al. demonstrate that a price tag affixed to a diagnostic test can influence physician behavior.1 This is not surprising, since physicians are, like anyone else, aware of the value of a dollar. The Medicare reimbursement rate for a given test was a reasonable choice for this price tag, since this is the “cost” (or “charge”) to the payer. But does awareness of charge (cost-consciousness) translate into the best care for patients? I am concerned that using price tags to change clinical practice is coercive rather than being value-conscious. As physicians, our effort to eliminate waste should be focused on using evidence-based diagnostic testing strategies that provide high-yield clinical data at a cost that patients and payers are willing to accept. One example from the inpatient setting of value-based decision-making is the removal of CK-MB from cardiac biomarker panels, since it adds limited clinical value over troponin.2 Price tags are coercive because physicians might interpret the cost as they would a personal out-of-pocket expense, rather than in relation to a patient or system’s annual healthcare expenditure. Another recent trial showed that a weekly flyer announcing “cost” to residents reduced lab utilization.3 Do residents perceive price tags differently than attending physicians? What if your patient is wealthy and self-pays? How does this influence the provider’s perception of an assay’s value or yield? Too many clinically unimportant factors render price tags on laboratory tests an arbitrary means of rationing. The majority of tests with price tags in the study by Horn et al. (over 80 % in both the high and low cost categories) were not reduced in utilization by the intervention. The authors do not speculate why some tests were affected and others were not. For example, if a patient and doctor in their study agreed to screen for prostate cancer using prostate-specific antigen (PSA) (one test that was not affected by the intervention) despite the controversial evidence that supports not doing this, did the issue of price even enter into their examination room decision? Certain healthcare networks or payers might someday remove PSA from outpatient screening based on the best available evidence, but this would be a rational decision, not individual rationing by price tag. Reducing laboratory utilization might have a role in cost-control, but let’s not confuse the ability to reduce test ordering for evidence that it is the right thing to do.
Third sound and NMR studies of helium mixtures in nuclepore

We report measurements of the third sound properties of3He–4He mixture films on Nuclepore. Using third sound resonance techniques, we measure the frequency, damping, amplitude and phase of third sound modes on a mixture film with a fixed coverage of4He, n4 = 0.39A−2, as a function of drive power, Pdr, 0.044 ≤ Pdr ≤ 440 nW, temperature, 40 ≤T ≤ 500 mK, and3He coverage, 0.01 ≤n3 ≤ 0.06A−2.Near T = 200 mK there is a sharp shift in the difference in phase, δΦ, between the drive voltage fluctuation and the film thickness fluctuation.
Positive and negative transfer in analogical problem solving by 6-year-old children

This study examined the relation between level of story representation (specific or abstract schema) and positive and negative analogical transfer and the effects of abstract schema training on problem solving in 6-year-olds. Subjects spontaneously transferred analogous solutions even when base and target problems shared few surface similarities. Abstract representation of the source analog was an important determinant of positive transfer; specific representations were not sufficient to facilitate generalization. Negative transfer occurred when the target problem involved a solution principle different from the base problems. Schema training markedly improved positive transfer; however, such training did not improve ability to discriminate the appropriateness of a solution principle in the negative training condition. The results indicate that both abstract representation of a solution principle and ability to determine when it should be applied are important aspects of effective transfer in problem solving.
Crystallographically Oriented Thin-Film Nanocrystalline Cathode Layers Prepared Without Exceeding 300°C

The highest capacity rf sputtered cathode layers created for use in thin-film solid-state batteries have been found to require an annealing step with temperatures in excess of 700°C. Since this high-temperature process step is incompatible with silicon device technology and flexible polymer substrates, the development of a low-process temperature (less than or equal to 300°C) cathode layer has been undertaken. Thin-film cathode layers consisting of LiCoO 2 were deposited using planar magnetron rf sputtering and subsequently incorporated into thin-film solid-state cells comprised of a LiPON electrolyte and lithium metal anode. Film composition was examined using Rutherford backscattering spectrometry and inductively coupled plasma mass spectroscopy, while phase content and crystal structure were studied through X-ray diffraction experiments conducted at the Stanford Synchrotron Radiation Laboratory. Microstructure and morphology were examined using transmission and scanning electron microscopy. It was found that LiCoO 2 could be deposited at room temperature in a nanocrystalline state with a defined (104) out of plane texture and a high degree of lattice distortion. By heating these layers to 300°C, the average grain size was increased while lattice distortion was minimized. Electrochemical cycling data revealed that the low temperature annealing step increases cell capacity to near theoretical values while significantly improving both the rate capability and discharge voltage. Impedance analysis on test cells showed that the electronic resistance of the cells is decreased after heating to 300°C.
Adaptive image sharpening using multiresolution representations

Image sharpening is defined as a process in which high-resolution information from one image is used to increase the spatial resolution of a second coregistered image of lower resolution. Image sharpening is of interest for applicaiton to multispectral and multisensor imagery. We present an adaptive technique to perform image sharpening based on the use of multiresolution image representations and neural networks. This technique is easily applied to provide resolution enhancement by powers of two and promises to accurately maintain the spectral characteristics of the original low-resolution image.
Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC.

Abstract The first committed step in lipid A biosynthesis is catalyzed by uridine diphosphate-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase, and inhibitors of LpxC may be useful in the development of antibacterial agents targeting a broad spectrum of Gram-negative bacteria. Here, we report the design of amphipathic benzoic acid derivatives that bind in the hydrophobic tunnel in the active site of LpxC. The hydrophobic tunnel accounts for the specificity of LpxC toward substrates and substrate analogues bearing a 3-O-myristoyl substituent. Simple benzoic acid derivatives bearing an aliphatic ‘tail’ bind in the hydrophobic tunnel with micromolar affinity despite the lack of a glucosamine ring like that of the substrate. However, although these benzoic acid derivatives each contain a negatively charged carboxylate ‘warhead’ intended to coordinate to the active site zinc ion, the 2.25 A resolution X-ray crystal structure of LpxC complexed with 3-(heptyloxy)benzoate reveals ‘backward’ binding in the hydrophobic tunnel, such that the benzoate moiety does not coordinate to zinc. Instead, it binds at the outer end of the hydrophobic tunnel. Interestingly, these ligands bind with affinities comparable to those measured for more complicated substrate analogue inhibitors containing glucosamine ring analogues and hydroxamate ‘warheads’ that coordinate to the active site zinc ion. We conclude that the intermolecular interactions in the hydrophobic tunnel dominate enzyme affinity in this series of benzoic acid derivatives.
Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD.

Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35–63). The conditioning regimen was myeloablative in 13 and non-myeloablative in 4 cases. GVHD occurred at a median of 49 days after transplant in 12 patients (range 21–231 days) and at a median of 46 days (range 25–119 days) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1–2 mg/kg/day of corticosteroids for a median of 7 days (range 2–26 days). They received a combination of daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). Of the 17 patients analyzed, 47% responded to treatment, 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all the patients died a median of 6.7 months (range 1.6–26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.
Bacterial expression, purification, and partial characterization of amino acids 94-155 of human tissue factor pathway inhibitor (TFPI) as an inhibitor of blood coagulation factor Xa.

Abstract Tissue factor pathway inhibitor (TFPI) is a plasma-derived protein which inhibits two of the active serine proteases present during normal blood coagulation. Inhibition of both of these proteases, factors VIIa and Xa, is thought to require a factor Xa-TFPI complex. To begin to investigate the interactions between factor Xa and TFPI, amino acids 94–155, which encode for the second Kunitz domain (K2) of TFPI, were expressed, purified, and partially characterized. Expression of the recombinant peptide was accomplished using an E. coli expression system which produced the peptide at an expression level of approximately 2–5% of total cell protein. The peptide was localized to disulfide-linked refractile bodies which were solubilized by reduction in the presence of denaturant and the soluble protein refolded. Oxidized K2 was purified from the refold mixture using a two-step procedure employing gel filtration chromatography and reverse-phase HPLC. The unprocessed form of the recombinant peptide, Met-Ala-K2 (rMA-K2), was characterized. This peptide was purified to apparent homogeneity as determined by SDS-PAGE, quantitative amino acid, Edman degradation, and electrospray mass spectrometry analyses (> 95% pure). The product bound to factor Xa covalently coupled to a solid support in the presence of 2M sodium chloride demonstrating its affinity for this enzyme. Preincubation of rMA-K2 peptide with factor Xa neutralized, with 1.1:1 stoichiometry, the ability of factor Xa to hydrolyze a small chromogenic substrate. Additionally, rMA-K2 prolonged the time to clot formation in a plasma-based assay dependent on factor Xa concentration. Finally, this peptide mildly prolonged the prothrombin and modified prothrombin times of normal pooled plasma. Taken together this data demonstrates that this region of TFPI inhibits factor Xa activity and allows for further characterization of this enzyme-inhibitor complex.
Density‐dependent mating tactics in the Grey hairstreak, Strymon melinus (Lepidoptera: Lycaenidae)

Male Grey hairstreak butterflies employed two different tactics, centred on palo verde trees growing on hilltops in central Arizona. During much of the spring flight season of about four months single males repelled all others from a perch tree. Interactions between the territorial resident in a tree and visiting intruder males were frequent but usually brief. One male retained possession of his perch for two weeks, although changes in ownership were generally much more frequent. But territorial behaviour was abandoned during periods when the number of intruders increased sharply, at which time perched males switched to non-aggressive patrolling about the preferred palo verdes. Females occasionally visited the palo verdes and interacted with males but no matings were observed. The mating system of the Grey hairstreak, like that of other similar landmark-defending insects, appears to have evolved in response to a diffusely distributed population of receptive females.
Capital budgeting with continuous cash flows: An application of calculus to managerial accounting

Abstract Project valuation in managerial accounting often involves discounting approximately continuous cash flows. Calculus is the natural mathematical tool for dealing with continuous flows and is a required part of the business curriculum in most major universities. Typical managerial accounting textbooks provide students with little opportunity to use calculus in solving accounting problems. Discounting continuous flows is a natural medium for introducing calculus into managerial accounting courses. This article illustrates the application of calculus to capital budgeting. Explicit but simplified consideration of inflation and taxation leads to interesting conclusions while maintaining enough simplicity for upper-division managerial accounting presentation
The Multiscale Modeling of Plastic Deformation in Metallic Nanolayered Composites

Metallic nanolayered composites exhibit very high flow strength and stable plastic flow to large strains. The explanation of the unusual mechanical behavior of these materials in terms of the atomic structures of the interfaces and layer thickness ranging from nanometers to micrometers requires atomistic simulations, dislocation theory, and crystal plasticity modeling across length scales.
Abstract 1269: Identifying Pten-sensitive drug therapy through metabolic phenotype-arrays

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The loss or mutation of tumor suppressor genes is a predominant event in the initiation, progression and metastatic development of cancer. PTEN and p53 are frequently inactivated in lethal metastatic prostate cancer, as they provide a critical growth, proliferation and anti-apoptotic advantage to cells in which their activity is diminished. In mouse prostate cancer models, loss of p53 alone in the prostate does not result in noticeable neoplasia. However, subsequent additional deletion of Pten causes lethal prostatic adenocarcinoma within 6 months, illustrating the need to combat the cooperative power of these two genetic lesions. Although inactivation of these tumor suppressor genes has been widely described at the level of their cancer phenotype, it has recently emerged that one understudied route to combat lesions harboring these alterations is to understand and exploit critical underlying changes in their metabolic makeup. In the present study, we used an array platform to determine the growth phenotype of p53 null Mouse Embryonic Fibroblast (MEFs) under close to 1200 conditions involving different sources of energy, amino acids, hormones, growth factors, chemical ions and responses to chemotherapy agents. with subsequent comparison to the response in p53/Pten double-null MEFs. Our analysis showed that loss of Pten critically altered response, utilization and sensitivity especially to specific hormones, ions and chemotherapy agents. Since this approach revealed Pten-status specific cell sensitivities, we are utilizing this information to establish selective targeting of cells as a precursor to therapeutic intervention in our genetically engineered mouse models of prostate cancer, which harbor the identical tumor suppressor lesions. Collectively, our results establish a rapid screening platform for identification of genotype-specific anti-cancer agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1269. doi:10.1158/1538-7445.AM2011-1269
Socioeconomic Position and Inflammatory and Immune Biomarkers of Cardiovascular Disease: Applications to the Panel Study of Income Dynamics

Biomarkers are an important aspect of research linking psychosocial stress and health. This article aims to characterize the biological pathways that may mediate the relationship between socioeconomic position (SEP) and cardiovascular disease (CVD) and address opportunities for further research within the Panel Study of Income Dynamics (PSID), with a focus on psychosocial stressors related to SEP. We review the literature on CVD biomarkers, including adhesion and proinflammatory molecules (interleukin-6, other cytokines, C-reactive proteins, fibrinogen, etc.) and microbial pathogens. The impact of socioeconomic determinants and related psychosocial stressors on CVD biomarkers mediated by behavioral and central nervous system pathways are described. We also address measurement and feasibility issues, including specimen collection methods, processing and storage procedures, laboratory error, and within-person variability. In conclusion, we suggest that PSID consider adding important assessments of specific ...
A pharmacokinetic evaluation of HIV protease inhibitors, cyclic ureas, in rats and dogs

The pharmacokinetics of a series of novel cyclic, non-peptide inhibitors of HIV protease were studied in rats or dogs after intravenous and oral administration. Six symmetrically substituted cyclic urea compounds (XK234, XM311, XM320, XM321, XM323, and XM412), which effectively inhibited HIV virus replication, with IC90 values of 0.03-1.0 microM (0.017-0.76 microgram mL-1), were evaluated. Plasma concentrations were measured in rats and dogs using specific and sensitive HPLC methods. In rats, the maximum plasma concentrations of 0.21-1.88 micrograms mL-1 were detected within 1 h of oral administration of 10 mg kg-1 of the compounds. The elimination half-lives ranged from 1.25 to 3.3 h in rats and the absolute oral bioavailability ranged from 18 to 100%. In dogs, the maximum plasma concentration and absolute oral bioavailability were 4.37 micrograms mL-1 and 48%, 1.07 micrograms mL-1 and 16%, and 1.48 mg ML-1 and 38% for XK234, XM311, and XM323, respectively. The data demonstrated that the maximum plasma concentrations of these cyclic ureas were several times higher than the IC90 for inhibition of viral replication after single doses of 10 mg kg-1 in rats and dogs. With this combination of high potency against virus replication and good oral bioavailability, these cyclic ureas represent a new class of compounds that are suitable for development as therapeutic agents for the treatment of HIV-associated diseases.
Burge on perception and sensation

In Origins of Objectivity Burge advances a theory of perception according to which perceptions are, themselves, objective representations. The possession of veridicality conditions by perceptual states—roughly, non-propositional analogues of truth-conditions—is central to Burge’s account of how perceptual states differ, empirically and metaphysically, from sensory states. Despite an impressive examination of the relevant empirical literatures, I argue here that Burge has not succeeded in securing a distinction between perception and “mere” sensation.
12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced c-Jun N-terminal Kinase (JNK) Phosphatase Renders Immortalized or Transformed Epithelial Cells Refractory to TPA-inducible JNK Activity *

c-Jun N-terminal kinase (JNK) regulates gene expression in response to various extracellular stimuli. JNK can be activated by the tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human oral keratinocytes but not in human keratinocytes that have been immortalized (HOK-16B and HaCaT) or transformed (HOK-16B-Bap-T) nor in a cervical carcinoma cell line (HeLa). The refractory JNK activation response to TPA is not due a defect in the JNK pathway, because JNK can be activated by other stimuli, e.g. UV irradiation and an alkylating agent N-methyl-N′-nitrosoguanidine in these immortalized or transformed cells. More importantly, the refractory JNK and JNKK activation response to TPA can be restored by treatment of the cells with a combination of TPA and a protein-tyrosine phosphatase inhibitor, sodium orthovanadate. Furthermore, pretreatment of cells with TPA partially inhibited UV- orN-methyl-N′-nitrosoguanidine-induced JNK activity. These results suggest that a TPA-inducible, orthovanadate-sensitive protein-tyrosine phosphatase may specifically down-regulate JNK signaling pathway in these immortalized/transformed epithelial cells. In contrast, ERK and p38/Mpk2 are not regulated by this TPA-induced phosphatase. This putative protein-tyrosine phosphatase appears to be JNK pathway-specific.
Complete correction of acid alpha-glucosidase deficiency in Pompe disease fibroblasts in vitro, and lysosomally targeted expression in neonatal rat cardiac and skeletal muscle.

The enzyme acid alpha-glucosidase catalyzes the breakdown of lysosomal glycogen. Absence of this enzyme results in infantile Pompe disease, characterized by hypertrophic cardiomyopathy, skeletal muscle weakness and fatal heart failure by 2 years of age. We have examined the possibility of gene replacement therapy for this disease, by constructing an E1-deleted recombinant adenovirus encoding human acid alpha-glucosidase (Ad-GAA). The dose-response in fibroblasts from patients with Pompe disease transduced with this vector is linear over the range tested (one to 2000 plaque forming units (p.f.u.) of Ad-GAA per cell), and acid alpha-glucosidase activity comparable to that of normal fibroblasts is achieved at 100 p.f.u. per cell. Targeting of the recombinant protein to the lysosomal compartment was confirmed by immunocytochemistry. In vivo expression was examined by injecting Ad-GAA into newborn rats; intracardiac administration produced 10 times the normal level of acid alpha-glucosidase activity in whole heart lysates, while a hind-limb i.m. injection increased activity in that muscle to six times the normal level. Western blotting of these tissues defected species at 76 kDa consistent with the size of processed lysosomal enzyme, and levels of expression as high as 1.0 mg recombinant protein per gram of tissue wet weight were produced. These data demonstrate high-level, lysosomal expression of recombinant acid alpha-glucosidase in treated target tissues and support the feasibility of gene replacement strategies for Pompe disease.
Low-affinity p75 nerve growth factor receptor expression in the embryonic monkey telencephalon: timing and localization in diverse cellular elements.

Abstract Monoclonal antibodies against the low-affinity (p75) subunit of the human nerve growth factor receptor have been used to determine the temporal appearance of this receptor and to identify the associated cellular elements in the developing occipital cortex of rhesus monkeys. Adult and fetal brains from embryos at embryonic days 45–121 were used. This embryonic time span includes periods of active neurogenesis, cell migration and initial formation of axonal connections in the cerebral cortex. The first immunolabeling in the developing cerebral wall was seen between embryonic days 56 and 64. The labeling was present in the transient subplate neurons, a small number of axonal processes and pericytes associated with blood vessels. By birth, labeled neurons of the subplate zone disappeared, but immunolabeled axonal processes could now be seen in large numbers in the cortex. These findings are consistent with the role of nerve growth factor in the coordination of cortical differentiation, but not with the initiation of neuronal proliferation, since the emergence of nerve growth factor receptor-labeled elements in the cortex occurs two to three weeks after the onset of neurogenesis in this species. Further, the diverse cellular elements labeled in the fetal cerebrum with the antibodies to the low-affinity nerve growth factor receptor suggests that a receptor or receptors associated with growth factor signaling for more than one growth factor family are recognized by these antibodies. Differential timing in the expression of families of growth factor receptors may be one mechanism by which developing neurons in the cerebral cortex could respond to the different signals which guide such processes as synaptogenesis and morphogenesis.
Rheological and Thermal Behavior of Gelled Hydrocarbon Fuels

Rocket propulsion systems are bound to energetic propellant combinations to provide the best performance in conjunction with smallest possible storage volume. The application of a gelled fuel and a gelled oxidizer potentially combines the advantages of conventional solid and liquid propellants without some specific disadvantages of both individual systems. Gelled JP-8 and RP-1 fuels have been used to study the rheological behavior of gelled hydrocarbons. For all investigations fumed silica was used as a gelling agentwith 4 to 7wt%.Alongside a description of the gel mixing process, the paper discusses viscosity, stability, thixotropic behavior, and the viscoelastic properties of the gels through their storage and loss moduli as a function of gelling-agent amount. An extended Herschel– Bulkley model was applied to describe the viscosity characteristics of the hydrocarbon gels. Differential scanning calorimetry measurements showed only a slight influence of the gelling-agent amount on the heat of vaporization of the gels. The ungelled hydrocarbons featured a higher heat of vaporization than the gels.
Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11β-hydroxysteroid dehydrogenase

The in vivo effect(s) of carbenoxolone (CS) on renal 11β-hydroxysteroid dehydrogenase (11β-OHSD), hepatic 11β-OHSD, and 5β-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11β-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11β-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11β-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11β-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 μM and 50 μM corticosterone, as was 5β-reductase (P < 0.05) using 4 μM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11β-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11β-OHSD and 5β-reductase with no inhibition of renal 11β-OHSD. We conclude that further experiments are necessary to determine whether CS truly inhibits renal 11β-OHSD in vivo, and whether hepatic handling of corticosterone also plays an important role in regulating its MC-like activity.
Activities of the oxide components in NioMnOMgO solid solutions

Abstract Activities of NiO in ternary NiOMnOMgO solid solutions have been determined experimentally at 1100 and 1300°C by equilibrating oxide samples with metallic Ni at controlled oxygen pressures of the atmosphere. Compositions of the oxide phase after equilibration were determined by X-ray d-spacing measurements. Activities of the two other components, MnO and NiO, were determined by ternary Gibbs-Duhem integrations.
The Wisconsin system for determining supplemental payments in foster care: A reliability study

Abstract In July of 1978 the State of Wisconsin implemented a new procedure for the determination of uniform foster care rates. The definitions and procedures used under the new policy are summarized in this brief note. Further, the findings of a study of the interrater reliability of the determination of the supplemental payment portion of the foster care rates are reported. The study found there was generally high accuracy and high interrater agreement among the rate-setters in determining the level of supplemental payment.
Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver.

1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4′-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4′-hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy.2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnit...
Methodological Issues in Research With Groups at High Risk for the Development of Schizophrenia

Research in schizophrenia has long been plagued by a major methodologic problem: Although countless studies have demonstrated differences between normal and schizophrenic subjects, it has not been possible to determine unequivocally whether these findings are the cause or the result of schizophrenia—a criticism that can be leveled at any study of the already manifest and diagnosed schizophrenic, whatever the research approach. This methodologic problem and a felt need to develop preventive techniques have led to a gradually increasing interest in the identification and study of persons who are at relatively high risk for the development of this disorder. The high-risk method circumvents many difficulties. In studying individuals prior to the development of manifest disorder, investigators can observe preexisting characteristics, making more possible the attribution of etiologic significance to abnormalities found in those individuals who subsequently develop schizophrenia. Even more importantly, this method, by making planned intervention feasible, may aid in the prevention of schizophrenia. Recognizing the potential importance of high-risk studies, the Center for Studies of Schizophrenia and the Adult Psychiatry Branch, both of NIMH, held a workshop in June 1969 to focus on the methodologic problems in research with groups at high risk for the development of schizophrenia. During the 2-day conference, 15 position papers were delivered and then discussed by 20 participants and 20 guests. This report is a brief summary of that conference. Attention was directed to three major areas: sampling and controls, measures, and research design and data analysis. Sampling and controls: At this writing, most investigators have focused on the offspring of a schizophrenic parent or parents in studies of groups at high risk. Whether such studies—with all the problems inherent in studying the offspring of psychotic parents (such as the effects of hospitalization, drugs, and foster care)— are the best approach to the problem is debatable, particularly in view of the probability that only 10-15 percent of the offspring will manifest schizophrenia in adulthood. Several alternative
Diagnosis by comparison with faulty comparators

Abstract This paper deals with a new approach to diagnosis by comparison. A new class of diagnosable systems is introduced: in these system, units and comparators used in the diagnostic process may fail. Failure of comparators introduces a new condition of test invalidation for a comparison operation. Characterization theorems and fault, identification similarities between different comparison models are presented.
Synthesis of an insulin analogue embodying a strongly fluorescent moiety, [19-Tryptophan-A] insulin

As part of our aim to study the conformation of insulin in solution by time-resolved fluorescence spectroscopy, we have synthesized the analogue [19-Tryptophan-A]insulin. In this compound, the tyrosine residue at position 19 of the A-chain of insulin, one of the most strongly conserved residues in insulins from various species, is substituted with the strongly fluorescent tryptophan residue. [19-Tryptophan-A]insulin displays 4.1 +/- 1.9% of the potency of natural insulin in binding to the insulin receptor from rat liver plasma membranes, 5.0 +/- 2.3% in stimulating lipogenesis in rat adipocytes, and 75.7 +/- 4% of the potency of insulin in radioimmunoassay. In connection with our previous work, these data indicate that an aromatic side chain at position A19 of insulin seems necessary but not sufficient for high biological activity. We further conclude that in regard to the immunogenic determinants of insulin, tryptophan in position A19 is an essentially neutral substitution for tyrosine in that position, in sharp contrast to the situation with regard to biological activity.
An A Priori Error Analysis of the hp-Version of the Continuous Galerkin FEM for Nonlinear Initial Value Problems

A continuous Galerkin finite element time-stepping method for the approximation of nonlinear initial value problems is analyzed within an hp-context. We derive a priori error bounds in the L2- and H1-norm that are explicit with respect to the time steps and the approximation orders. In particular, it is shown that, for analytic solutions (with certain possible start-up singularities) exponential convergence rates can be achieved. Moreover, we prove that the scheme superconverges at the nodal points of the time partition. Numerical experiments illustrate the performance of the method.
Apparent Survival Rates of Forest Birds in Eastern Ecuador Revisited: Improvement in Precision but No Change in Estimates

Knowledge of survival rates of Neotropical landbirds remains limited, with estimates of apparent survival available from relatively few sites and species. Previously, capture-mark-recapture models were used to estimate apparent survival of 31 species (30 passerines, 1 Trochilidae) from eastern Ecuador based on data collected from 2001 to 2006. Here, estimates are updated with data from 2001-2012 to determine how additional years of data affect estimates; estimates for six additional species are provided. Models assuming constant survival had highest support for 19 of 31 species when based on 12 years of data compared to 27 when based on six; models incorporating effects of transients had the highest support for 12 of 31 species compared to four when based on 12 and six years, respectively. Average apparent survival based on the most highly-supported model (based on model averaging, when appropriate) was 0.59 (6 0.02 SE) across 30 species of passerines when based on 12 years and 0.57 (6 0.02) when based on six. Standard errors of survival estimates based on 12 years were approximately half those based on six years. Of 31 species in both data sets, estimates of apparent survival were somewhat lower for 13, somewhat higher for 17, and remained unchanged for one; confidence intervals for estimates based on six and 12 years of data overlapped for all species. Results indicate that estimates of apparent survival are comparable but more precise when based on longer-term data sets; standard error of the estimates was negatively correlated with numbers of captures (rs= 20.72) and recaptures (rs= 20.93, P,0.001 in both cases). Thus, reasonable estimates of apparent survival may be obtained with relatively few years of data if sample sizes are sufficient.
Integrating the Crisis Management Perspective into the Strategic Management Process

The fields of strategic management and crisis management have been evolving separately despite their potential for synergistic integration. This paper explicates how adding crisis management's defensive/preventative capability to strategic management's offensive market positioning orientation can yield a more comprehensive approach to the strategic management of organizations. The traditional strategic management process is reviewed first and then analysed with respect to the gap that exists in this orientation. Examining the differences and similarities in perspectives between strategic management and crisis management and then reviewing the crisis management process provides a basis to proceed with a synthesis of the two fields. The paper concludes with the presentation of a new integrated strategic management process model that pushes forward the boundaries of strategic management and internalizes crisis management activities into that process.
A conditional maximized sequential probability ratio test for Pharmacovigilance

The importance of post-marketing surveillance for drug and vaccine safety is well recognized as rare but serious adverse events may not be detected in pre-approval clinical trials. In such surveillance, a sequential test is preferable, in order to detect potential problems as soon as possible. Various sequential probability ratio tests (SPRT) have been applied in near real-time vaccine and drug safety surveillance, including Wald's classical SPRT with a single alternative and the Poisson-based maximized SPRT (MaxSPRT) with a composite alternative. These methods require that the expected number of events under the null hypothesis is known as a function of time t. In practice, the expected counts are usually estimated from historical data. When a large sample size from the historical data is lacking, the SPRTs are biased due to the variance in the estimate of the expected number of events. We present a conditional maximized sequential probability ratio test (CMaxSPRT), which adjusts for the uncertainty in the expected counts. Our test incorporates the randomness and variability from both the historical data and the surveillance population. Evaluations of the statistical power for CMaxSPRT are presented under different scenarios.
Protein Kinase CK1αLS Promotes Vascular Cell Proliferation and Intimal Hyperplasia

Protein kinase CK1α regulates several fundamental cellular processes including proliferation and differentiation. Up to four forms of this kinase are expressed in vertebrates resulting from alternative splicing of exons; these exons encode either the L-insert located within the catalytic domain or the S-insert located at the C terminus of the protein. Whereas the L-insert is known to target the kinase to the nucleus, the functional significance of nuclear CK1αLS has been unclear. Here we demonstrate that selective L-insert-targeted short hairpin small interfering RNA-mediated knockdown of CK1αLS in human vascular endothelial cells and vascular smooth muscle cells impairs proliferation and abolishes hydrogen peroxide-stimulated proliferation of vascular smooth muscle cells, with the cells accumulating in G 0 /G 1 . In addition, selective knockdown of CK1αLS in cultured human arteries inhibits vascular activation, preventing smooth muscle cell proliferation, intimal hyperplasia, and proteoglycan deposition. Knockdown of CK1αLS results in the harmonious down-regulation of its target substrate heterogeneous nuclear ribonucleoprotein C and results in the altered expression or alternative splicing of key genes involved in cellular activation including CXCR4, MMP3, CSF2, and SMURF1. Our results indicate that the nuclear form of CK1α in humans, CK1αLS, plays a critical role in vascular cell proliferation, cellular activation, and hydrogen peroxide-mediated mitogenic signal transduction.
THE OPERATIONS DASHBOARD: A COLLABORATIVE ENVIRONMENT FOR MONITORING VIRTUAL ORGANIZATION-SPECIFIC COMPUTE ELEMENT OPERATIONAL STATUS

Grid computing integrates heterogeneous, geographically distributed, Internet-ready resources that are administered under multiple domains. A key challenge in grid computing is to provide a high quality of service to users in a transparent fashion, hiding issues that include ownership, administration, and geographic location of a wide variety of resources that provide compute cycles, data storage, rendering cycles, imaging devices, and sensors, to name a few. Ensuring the functionality of a wide variety of resources under multiple administrative policies requires tools for discovering, repairing, and publishing information on the services offered by individual sites within a given grid. In this paper, we present the ACDC Operations Dashboard, an interactive, collaborative environment for collecting, addressing, and publishing operational service information for resources across a computational grid.
Killing Time: The World Politics of Civil War Duration, 1820–1992

Policymakers often trumpet the potential for third parties to stop the killing associated with civil wars, yet third parties as strategic actors also have incentives to encourage longer civil wars. We argue that in order to assess the influence of third parties on civil war duration, it is necessary to consider the interdependent nature of third party interventions as they are distributed across the set of civil war combatants. We also argue that it is important to consider the geopolitical context in which civil wars occur, rather than focusing solely on characteristics internal to these conflicts. To test our hypotheses about the impact of third parties and geopolitical factors on civil war duration, we rely on event history analysis and a sample of 152 civil wars for the period 1820–1992. We find empirical support for the idea that extremely long civil wars correspond to the equitable distribution of third party interventions—stalemates prolong wars. The analysis also indicates that separatist civil wars and ongoing civil wars in states proximate to the civil war state result in civil wars of longer duration. Finally, we find that when third parties raise the stakes of the conflict by engaging in the use of militarized force against the civil war state, the duration of these conflicts is reduced. In general, our analysis underscores the importance of modeling the interdependent and dynamic aspects of third party intervention as well as the world politics of civil wars when forecasting their duration and formulating policy.
Developing Effective Leadership Skills

This review examines two practice-oriented collections of articles on how civil servants can develop effective leadership skills In the past decade, the nature of public leadership has changed dramatically, a shift recently analyzed in the book Transforming Public Leadership in the 21st Century (Morse, Buss, and Kinghorn 2007) The two books under review focus on how public sector managers can harness these changes to become better leaders This review examines the advice that each set of contributors offers