cssi/SciSciGPT-SciSciNet huggingface dataset:
Rosiglitazone disrupts endosteal bone formation during distraction osteogenesis by local adipocytic infiltration.

Abstract Rosiglitazone (Rosi) is a drug in the thiazolidinedione class for treatment of type 2 diabetes mellitus (T2DM), which binds and activates PPARγ nuclear receptor in fat cells, sensitizing them to insulin. Despite proven antidiabetic efficacy, Rosi therapy may be associated with trabecular bone loss and an increased risk of fractures. To examine the potential side effects of Rosi treatment on bone formation, we delivered Rosi to mice using a combined model of distraction osteogenesis (DO) and type 2 diabetes mellitus (T2DM). DO provides a unique method to isolate the sequence of intramembranous bone formation, an important component of both fracture healing and bone homeostasis. Four groups of n = 6 mice were used to compare the effects of Rosi on bone formation and cellular composition in both diabetic (Avy/a strain) and non-diabetic mice (a/a strain). New bone formation was examined by high resolution radiographs, micro-computed tomography, and histology. Precursor cells in the distraction gap were quantitated using immunohistochemical stains for proliferating cell nuclear antigen. Committed osteoblasts and adipocytes in the gap were identified and quantitated by immunostaining for osteocalcin and FABP4/aP2, respectively. The diabetic model developed obesity, hyperglycemia, hyperinsulinemia and insulin resistance, while the control littermates remained lean, normoglycemic and insulin sensitive. Rosi treatment decreased levels of non-fasted glucose and insulin and improved insulin sensitivity in the Avy/a mice, but had no effect in a/a mice, indicating antidiabetic efficacy of Rosi at the tested dose. Despite the diabetic, obese mice having twice the number of fat cells in their marrow than the non-diabetic mice, bone formation using DO was not adversely affected by the diabetes itself. However, Rosi treatment significantly diminished intramembranous endosteal bone formation, while increasing adipogenesis in and adjacent to the distraction gap up to 3.5- to 3.8-fold in both diabetic and non-diabetic models. This effect was independent of the anti-diabetic therapeutic response. These results raise the question of whether osteoblast precursors are inhibited in their development or actually converted to adipocytic phenotypes, possibly via marrow fat PPARγ nuclear receptor.
Feedback Inhibition and Product Complexes of Recombinant Mouse Muscle Adenylosuccinate Synthetase

Adenylosuccinate synthetase governs the committed step of AMP biosynthesis, the generation of 6-phosphoryl-IMP from GTP and IMP followed by the formation of adenylosuccinate from 6-phosphoryl-IMP and l-aspartate. The enzyme is subject to feedback inhibition by AMP and adenylosuccinate, but crystallographic complexes of the mouse muscle synthetase presented here infer mechanisms of inhibition that involve potentially synergistic ligand combinations. AMP alone adopts the productive binding mode of IMP and yet stabilizes the active site in a conformation that favors the binding of Mg(2+)-IMP to the GTP pocket. On the other hand, AMP, in the presence of GDP, orthophosphate, and Mg(2+), adopts the binding mode of adenylosuccinate. Depending on circumstances then, AMP behaves as an analogue of IMP or as an analogue of adenylosuccinate. The complex of adenylosuccinate.GDP.Mg(2+).sulfate, the first structure of an adenylosuccinate-bound synthetase, reveals significant geometric distortions and tight nonbonded contacts relevant to the proposed catalytic mechanism. Adenylosuccinate forms from 6-phosphoryl-IMP and l-aspartate by the movement of the purine ring into the alpha-amino group of l-aspartate.
Characterizing small fatigue cracks in metallic alloys

Small fatigue cracks grow faster than large fatigue cracks and below the large-crack threshold, and it is necessary to include these characteristics in many life-prediction models. Numerous micromechanics experimental measurements have been made to determine the origin of this anomalous small-crack behavior and to unify and predict small- and large-crack growth-rate behavior. Micromechanics showed that a stress-intensity factor described the crack-opening displacement (COD). Four methods for characterizing small-fatigue-crack behavior are reviewed: three based on fracture mechanics and one empirical. The three fracture mechanics-based methods are essentially complementary to each other and allow prediction of small-crack growth-rate behavior.
Antitrust and Liberalization in developing countries

A number of developing countries around the world have recently liberalized once highly protected regimes through privatization programs and by reducing impediments to market trade. Many of these countries have adopted an antitrust policy as an integral component of their market reforms. Recent assessments of trade liberalization programs show disappointing results. Such outcomes contradict long-held beliefs that free trade is sufficient to generate competitive outcomes in small economies. Antitrust advocates view these underwhelming achievements as further justification for extensive antitrust enforcement. We argue instead that the failure of liberalization suggests not the correctness but the inappropriateness of the enactment of antitrust policies. The continuance of market power after liberalization is due primarily to lobbying activities by producer interest groups to establish nontariff barriers rather than to collusive practices among producers. Interest groups find cartelization and rent seeking a...
Global Pressures, National Policies, and Labor Rights in Latin America

This paper examines the impact of countervailing external pressures on labor rights in 17 Latin American countries. On the one hand, these countries have been urged to reform their labor laws and practices to comply with international labor standards, including protections for the collective rights of workers. On the other hand, they have been pressured to adopt more flexible labor markets, which often undermine collective labor organization. After dividing the countries by the type of political regime that prevailed when the pattern of relations between labor and the state was being established, the paper presents and explains the results of indices created to measure two outcomes: labor standards and labor market flexibility. It then analyzes the impact of four types of external actors (the ILO, national governments pursuing trade agreements, multinational corporations, and international financial institutions) on these outcomes, both de jure and de facto. The paper's main finding is that these actors have had an impact on labor outcomes in the region, but that their influence is heavily mediated by domestic factors, particularly historical legacies of state-labor relations.
Comparison of echo state network and extreme learning machine for PV power prediction

The increasing use of solar power as a source of electricity has introduced various challenges to the grid operator due to the high PV power variability. The energy management systems in electric utility control centers make several decisions at different time scales. In this paper, power output predictions of a large photovoltaic (PV) plant at eight different time instances, ranging from few seconds to a minute plus, is presented. The predictions are provided by two learning networks: an echo state network (ESN) and an extreme learning machine (ELM). The predictions are based on current solar irradiance, temperature and PV plant power output. A real-time study is performed using a real-time and actual weather profiles and a real-time simulation of a large PV plant. Typical ESN and ELM prediction results are compared under varying weather conditions.
RADIATION AND VELOCITY FIELDS INDUCED BY LOCALIZED TEMPERATURE FLUCTUATIONS

A theory describing the coupling between radiative transport, thermal conduction, and velocity fluctuations in postcombustion gases is described. The emission and absorption of radiant energy are taken to be dominated by soot, distributed uniformly in space. The theory is local in the sense that the gas is assumed to be unbounded. However, the temperature, velocity, and radiation fields can be both three-dimensional and time-dependent. Moreover, the model can be thought of as describing any postcombustion scenario in which the absorption coefficient is spatially uniform. Within the framework of the low Mach number combustion equations, an exact representation of the velocity and radiation fields instantaneously induced by fluctuations of any magnitude in the temperature is presented. This result is used to derive a single scalar integro-differential equation for the temperature that incorporates the conservation of mass and energy, together with an exact solution of the radiative transport equation. Some consequences of the theory are illustrated by studying the response generated by a spherically burning fuel mass.
The effect of perceived distance on induced movement

The magnitude of induced movement was measured as a function of the perceived depth between the test object and the plane of the induction object, with this perceived depth produced by stereoscopic cues. Three experiments were conducted. In each experiment, the induction object (a frame of constant physical size) was positioned at one of three distances with the test object (a point of light) placed successively at each of the three distances. Predictions of the magnitude of induction as a function of the depth separation of the test and induction object were made from the subject-relative and object-relative hypotheses of induced motion. It was expected, however, that neither of these hypotheses would predict the results independently of a factor described in the adjacency principle. This principle states that the effectiveness of whatever cues or processes determine the induced movement will decrease with increased depth between the test and induction object. The data indicate that the adjacency principle must be considered in explaining the results. The subject-relative rather than object-relative hypothesis as modified by the adjacency principle was most successful in predicting the results. Control conditions in which the frame was stationary and the point of light was physically moving were also used. Despite the fact that the relative displacement of the objects on the eye in the experimental and control conditions were the same, the results indicate that O could distinguish between these two kinds of conditions. Although the apparent movement was greater in the control conditions than in the experimental conditions, the reverse is true if the total perceived movement of the test and induction object are considered together.
FATTY ACID DISCRIMINATION AND OMEGA -HYDROXYLATION BY CYTOCHROME P450 4A1 AND A CYTOCHROME P4504A1/NADPH-P450 REDUCTASE FUSION PROTEIN

The omega-hydroxylation of fatty acids by certain cytochrome P450 enzymes shows a degree of chain-length and regionspecificity which is remarkable in view of the conformational flexibility of these substrates, the strong similarity in properties among homologs, and the lack of polar groups (other than the carboxy terminus) with which to guide and strength enzyme-substrate interactions. To investigate the chemical basis for these features of omega-hydroxylation we designed and synthesized a series of lauric acid analogs and evaluated them as substrates and inhibitors of omega-hydroxylation catalyzed by cytochrome P4504A1 and a cytochrome P450 4A1/NADPH-P450 reductase fusion protein. Among n-alkanoic acids, lauric acid was found to have the optimum chain length for the fusion protein, as it does for native cytochrome P450 4A1. With both enzymes, chain shortening caused a precipitous drop in turnover while chain lengthening caused a gradual drop in turnover. The fusion protein omega-hydroxylated methyl laurate and lauryl alcohol about 1/10th as efficiently as lauric acid, but it did not hydroxylate lauramide. 10-Methoxydecanoic acid underwent O-demethylation (via omega-hydroxylation). The branched substrate 11-methyllauric acid was hydroxylated efficiently and selectively at the omega-position. In contrast, the cyclopropyl analog 11,12-methanolauric acid was not detectably hydroxylated, although it induced Type I binding spectrum and inhibited lauric acid omega-hydroxylation by 43% at equimolar concentrations. omega-(Imidazolyl)-decanoic acid induced a Type II heme-binding spectrum and was an especially potent inhibitor of lauric acid hydroxylation. Collectively these data suggest that the active site of cytochrome P450 4A1 has an elongated tubular shape of definite length (ca. 14 A) with a recognition site for polar groups (including but not limited to carboxyl) at its entrance and the (oxo)heme group at its terminus.
Therapy with TLR7 agonists induces lymphopenia: correlating pharmacology to mechanism in a mouse model.

Synthetic TLR7 agonists have been proposed as oral replacements for interferonα (IFNα) therapy in the treatment of hepatitis C virus infection. However, adverse effects, such as lymphopenia and cardiovascular irregularities, have been observed in the clinical following treatment with TLR7 agonists. We wished to understand and characterise the relationship between TLR7 agonism and adverse effects. We compared responses to two prototypic TLR7 agonists (Resiquimod: R-848; and PF-04878691) in a mouse model and compared the responses to treatment with IFNα. We measured clinically relevant adverse effects such as lymphopenia and cardiovascular irregularities and related them to plasma drug levels and clinically relevant efficacy biomarkers such as the pro-inflammatory cytokine IP-10, 2’5’OAS and TLR7 receptor expression. By 2 h post dose all agents had induced a dose-dependent transient lymphopenia. IFNα increased heart rate immediately following dosing, persisting for 5 h, whilst PF-04878691 induced significant reductions in blood pressure. Lymphopenia co-incided with maximum plasma drug levels, raised levels of IP-10 and the auto-induction of TLR7 expression in the blood and lymph nodes. Peak levels of 2’5’OAS occurred at 24 h post-dose and only at doses which also induced lymphopenia. We conclude that systemic delivery of TLR7 agonists or IFNα induces similar exaggerated pharmacology, consistent with there being a narrow therapeutic window between efficacy and safety. This clinically validated mouse model will help to investigate whether more potent agonists or optimised dosing schedules, will be successful strategies for targeting TLR7 in patients.
The effects of massage therapy alone and in combination with other complementary therapies on immune system measures and quality of life in human immunodeficiency virus.

Objectives: Determine effects of massage therapy alone and in combination with exercise or stress management-biofeedback treatment on enumerative immune measures, and quality of life in moderately ...
Mechanical injury to neuronal/glial cultures in microplates: Role of NMDA receptors and pH in secondary neuronal cell death

In vitro models of traumatic injury are useful adjuncts to animal models for studying mechanisms of post-traumatic cell death. Here we describe a new in vitro model in which reproducible levels of injury are delivered by a punch device that produces 28 parallel cuts in individual wells of 96-well microplates. Cell loss is measured by LDH assay or quantitative fluorometric assay for ethidium homodimer staining. Glial cultures show cell death restricted to the initial injury site, whereas neuronal/glial cultures demonstrate substantial spread of cell loss over time. We used this model to examine the role of pH and NMDA receptors in delayed post-traumatic injury. NMDA receptor blockade by dizocilpine (MK-801) or treatment with antisense oligodeoxynucleotides directed against NMDAR1 was neuroprotective. Decreased cell death was observed under acidic conditions whereas increased extracellular pH was associated with increased, MK-801 sensitive cell loss. Advantages of our model include: reproducible trauma induction; rapid measurements of cell injury; and use of 96-well microplates which reduce time and cost. This model appears to be well-suited for the study of selected mechanisms of post-traumatic neuronal injury as well as for screening potential neuroprotective agents.
One-electron oxidation of L2PdII(CH3)2 complexes: Ligand effects on production of ethane vs. Pd–C bond homolysis

Abstract Dimethyl palladium(II) complexes with various bi- and tri-dentate ligands, (L2)PdII(CH3)2, react readily with the one-electron oxidant ferrocenium hexafluorophosphate (Fc+) in acetone-d6. These oxidations typically proceed by one of two pathways. Oxidatively-induced methyl transfer forms trimethyl palladium(IV) intermediates which usually undergo reductive C−C coupling and form ethane. Alternatively, oxidation can cause Pd–C bond homolysis, which yields predominantly methane and methylferrocene, a product of methyl radical trapping. The reaction selectivity is dependent on ligand identity and likely due to the ability of different classes of ligands to stabilize intermediates in the PdIV oxidation state. Complexes containing the bidentate diimine ligands 1,10-phenanthroline (phen) or 2,3-dimethyl-1,4-di-4-tolyl-1,4-diazabuta-1,3-diene (Tol2DAB) adhere to the ethane producing pathway previously reported for (tBu2bpy)Pd(CH3)2 (tBu2bpy = 4,4′-bis(tert-butyl)-2,2′-bipyridine), as does the complex of the potentially tridentate 6-methyl-N,N′-bis-2-pyridinyl-2-pyridinamine ligand. In contrast, Fc+ oxidations of complexes with bis-carbene (1,1′-methylene-3,3′-tert-butyldiimidazole-2,2′-diylidene, tBuCCtBu), bis-phosphine (tert-butyl-bis(diphenylphosphinomethyl)amine (tBuN(CH2PPh2)2, PCNCP), or tris(pyrazolyl)methane ligands resulted in little or no ethane production. These reactions likely involve either methyl radicals or trimethyl PdIV complexes that are stable towards C−C reductive elimination. Oxidation of (TMEDA)Pd(CH3)2 (TMEDA = (N,N,N′,N′-tetramethylethylenediamine) yields both methane and ethane, suggesting that both Pd–C bond homolysis and oxidative methyl transfer are competitive in this case.
Fragmentation and Sprawl: Evidence from Interregional Analysis

Recent years have witnessed widespread expansion of state and regional planning programs in the United States. A major purpose of these efforts is to reduce urban sprawl—low density, discontinuous, suburban–style development, often characterized as the result of rapid, unplanned, and/or uncoordinated growth— by promoting jurisdictional cooperation and regulatory consistency across metropolitan areas. This paper evaluates the efficacy of this approach by examining the relationship between governmental fragmentation and several measurable outcomes of urban development: density, urbanized land area, property value, and public expenditures on infrastructure. The four dimensions are modeled in a simultaneous equations framework, providing substantive evidence on how fragmentation and other exogenous factors affect metropolitan growth patterns. Fragmentation is associated with lower densities and higher property values, but has no direct effect on public service expenditures; less fragmented metropolitan areas occupy greater amounts of land due to the extensive annexation needed to bring new development under the control of a central municipality. The findings of the analysis lend support to state and regional planning efforts aimed at increasing cooperation among local governments, but also suggest that further research is needed in order to evaluate whether or not they produce their intended effects.
Experimental bias: Task, tools, and time

In any experiment, control over all possible variables affecting the response is rarely, if ever, possible. Even in a laboratory setting it is difficult to control all variables which might conceivably affect the outcome. This study identifies three variables—task relevancy, tool availability, and time allocation as variables which have potentially reactive effects in laboratory experiments.
Finite Instantiations for Integer Difference Logic

The last few years have seen the advent of a new breed of decision procedures for various fragments of first-order logic based on propositional abstraction. A lazy satisfiability checker for a given fragment of first-order logic invokes a theory-specific decision procedure (a theory solver) on (partial) satisfying assignments for the abstraction. If the assignment is found to be consistent in the given theory, then a model for the original formula has been found. Otherwise, a refinement of the propositional abstraction is extracted from the proof of inconsistency and the search is resumed. We describe a theory solver for integer difference logic that is effective when the formula to be decided contains equality and disequality (negated equality) constraints so that the decision problem partakes of the nature of the pigeonhole problem. We propose a reduction of the problem to propositional satisfiability by computing bounds on a sufficient subset of solutions, and present experimental evidence for the efficiency of this approach.
Changes in nucleic acid content and distribution during cotton embryogenesis

Abstract Quantitative estimation of RNA and DNA content per cell of the developing cotton embryo was made. Both DNA and RNA content per embryo increased with increase in embryo size. However, the DNA and RNA content per cell decreased as embryogenesis proceeded. Evidence for the presence of cytoplasmic DNA was presented from two different methods, i.e., chemical analysis and autoradiography. As the embryo became mature the localization of DNA became exclusively nuclear. Exogenous uridine and thymidine were incorporated by embryos of all stages of development. Osmotic concentration appeared to be the single physical factor limiting the incorporation of uridine and thymidine. The effect of different concentrations of mannitol was studied. Actinomycin D completely blocked the uridine incorporation and increased the stainability of nuclei by Azure B. The inhibitory effect of IUDR on thymidine incorporation was also examined.
Gonadal hormones modulate sex differences in judgments of relative numerousness in meadow voles, Microtus pennsylvanicus

Animals in a variety of taxa discriminate between a greater quantity and a lesser quantity of the same object, an ability that is referred to as relative numerousness judgment. For example, meadow voles can distinguish between areas containing more over-marks by one opposite-sex scent donor and fewer over-marks by another opposite-sex scent donor. Females appear to be able to make better discriminations between more or less over-marks than do males. In that gonadal hormones have been implicated in modulating cognitive function associated with spatial tasks, we tested the hypothesis that high titers of testosterone and estradiol are necessary for male and female voles, respectively, to distinguish between the top- and bottom-scent donors in an area containing mixed over-marks. We gonadectomized voles, giving them either gonadal hormone replacement (testosterone for males and estradiol for females) or no hormone replacement, and tested their spontaneous judgments of distinguishing between the top- and bottom-scent donors in an area containing mixed over-marks; a task involving judgments of relative numerousness. Female voles given replacement estradiol performed better than did female voles not given replacement estradiol in determining the top-scent and bottom-scent males in areas containing mixed over-marks. In contrast, males not treated with replacement testosterone performed better than did males treated with testosterone in determining the top-scent and bottom-scent males in areas containing mixed over-marks. Thus, high titers of estradiol and low titers of testosterone are associated with better performance on tasks involving relative numerousness in female and male voles, respectively. The results of this task on relative numerousness judgments are discussed in relation to the effects of gonadal steroid hormone on spatial ability, a closely related cognitive domain, and the social biology of meadow voles.
What is Real in the Age of Virtual Reality?“Retraining” Frame Analysis for a Technological World

How do social actors determine what is really happening and what is not? This distinction, analyzed in such depth by Erving Goffman in Frame Analysis, now requires further analysis as technologies such as virtual reality become ever more affordable and available, transforming many aspects of everyday life and, inevitably, the definition of the “real” experience itself. This article considers the ways that experience is generated and organized in modern social life, arguing that a “refraining” of frame analysis and a “reconceptualization” of reality itself is necessary to help us understand the ways in which social worlds involving highly sophisticated technologies are created and endowed with meaning by actors, as well as the subtle, long-term effects of such technologies.
Applied mathematics: How chaos forgets and remembers

“It is difficult to make predictions, especially about the future,” goes the proverb. A study of the dynamics of chaotic systems in the context of information theory adds a twist to this saying.
Intelligent home risk assessment systems and integration with biometric identification

An overview is given of the Home of the 21 st Century Laboratory. The laboratory is operated as a joint program with America-On-Line and George Washington University. The program is described with illustrations and discussion of the systems that are part of the laboratory. The concept of application for face recognition systems in the intelligent home of the future is presented and some initial approaches in using biometrics are shown. Issues of privacy and sharing of information within and outside the home are addressed. Issues include safety and security concerns vs. inappropriate observations of activities in and outside the home. Technology options currently available for application in the home are described and assessed.
Local superconducting coupling in the strong-localization limit of ultrathin granular metal films

The onset of fluctuations into the superconducting state, as identified bythe appearance of a local minimum in the resistance versus temperature, isfound to be coincident with the characteristic activation energy ofnormal-state conduction falling to a value of the order of the superconductingenergy gap of the material at /ital T/=0. The model of conduction used isvariable-range hopping with a Coulomb gap, appropriate to granular metals.
Microbial contributions to the evolution of the 'steady state' carbon dioxide system.

Various processes for the production of carbon dioxide by microorganisms are presented. It is postulated that a ‘microniche’ developed in a reducing environment; a symbiotic relationship between alga-like organisms and bacterium-like organisms in the ‘microniche’ governed the production of carbon dioxide resulting in the establishment of the steady state carbon dioxide system in the sea.
Experimental Study on Bearing Characteristics of the Pad and Chimney Foundation in Salt Lake Area

Transmission line foundation engineering inevitably encounters the special geological conditions in salt lake area, such as strong corrosion of saline soil, weakness of foundation soil and high water table of groundwater. In-situ tests on bearing characteristics of the selected pad and chimney foundation were conducted. Ultimate uplift bearing capacity and ultimate compressive bearing capacity of the pad and chimney foundation in salt lake are obtained, which can verify the rationality and reliability for its engineering popularization.
Limit Distributions of Directionally Reinforced Random Walks

Abstract As a mathematical model for time and space correlations in ocean surface wave fields, Mauldin, Monticino, and von Weizsacker (1996,Adv. in Math.117, 239–252), introduced directionally reinforced random walks and analyzed their recurrence properties. This paper develops limiting properties for these random walks inRd. In particular, it is shown that the limit distribution is a Brownian motion if the time between changes of directions has a finite second moment, and is a stable process if the time between changes of directions is in a domain of attraction of a stable law. The latter gives an affirmative answer to an open question posed by Mauldinet al.. The strong law of large numbers and strong approximations are also discussed.
Dynamic meshless method applied to nonlocal crack problems

The dynamic meshless methods for local and nonlocal field theories are formulated in this paper. Application to two crack problems is presented. The meshless method of local theory gives solution that is in good agreement with the classical analytical crack tip solution, while the nonlocal theory yields a solution without stress singularity at the crack tip. The numerical results also show the embedded nonlocal nature of meshless methods.
Long-range correlations in nucleus-nucleus interactions at ultrahigh energies

Results on long-range correlations of the shower particles in the pseudorapidity space are presented for the first time for 124, 191, and 153 nearly central events produced, respectively, by sulphur and oxygen beams at 200 GeV/nucleon and an oxygen beam at 60 GeV/nucleon, in nuclear emulsion.
Total Quality Performance of Design/Build Firms Using Quality Function Deployment

The belief that the design-build (D/B) project delivery system does not lend itself to effective quality assurance and control is quite common in construction circles. Total quality consists of: (1) the corporate quality culture; (2) the quality of the project service; and (3) the quality of the constructed facility. This paper describes a model that was developed to measure the total quality of a D/B firm using quality function deployment (QFD). The first part of this model is described elsewhere and measures the effectiveness of the corporate quality culture and the quality of the service when delivering a project by using QFD. The second part of the model is described in this paper. It makes use of eight building quality factors, three building performance factors, and the relationships between building quality and performance factors (obtained from building users/evaluators) and it measures the quality performance of the constructed facility by using QFD. A total quality performance index is generated by combining the quality performance at the corporate, project, and product levels. The total quality performance measurement model described in this paper can be used by D/B firms to benchmark themselves against their competitors or to monitor their own performance. It can also be used by owners to rank D/B firms relative to their total quality performance.
Metabolism via the pentose phosphate pathway in rat pheochromocytoma PC12 cells: Effects of nerve growth factor and 6-aminonicotinamide

Exposure of rat pheochromocytoma PC12 cells to 0.1 mM 6-aminonicotinamide (6AN) for 24 hours resulted in a 500-fold increase in 6-phosphogluconate indicating active metabolism of glucose via the oxidative enzymes of the pentose phosphate pathway. Amounts of 6-phosphogluconate that accumulated in 6AN-treated cells at 24 hours were significantly increased by treatment of the cells with nerve growth factor (NGF) (100 ng 7S/ml) suggesting that metabolism of glucose via the pentose pathway at this time was enhanced by NGF. This stimulation of metabolism via the pentose pathway is probably a late response to NGF because initial rates of 6-phosphogluconate accumulation in 6AN-treated cells were the same in the presence and absence of NGF. Moreover, amounts of14CO2 generated from 1-[14CO2]glucose during the initial six hour incubation period were the same in control and NGF-treated cells. Specific activities of hexose phosphates labeled from 1-[14CO2]glucose were also the same in control and NGF-treated cells. The observation that 6AN inhibited metabolism via the pentose phosphate pathway but failed to inhibit NGF-stimulated neurite outgrowth suggests that NADPH required for lipid biosynthesis accompanying NGF-stimulated neurite outgrowth from PC12 cells can be derived from sources other than, or in addition to, the oxidative enzymes of the pentose phosphate pathway.
A neutrally buoyant sphere in creeping flow between parallel plates: farfield velocity profiles

Abstract The farfield creeping flow around a sphere suspended in Poiseuille flow between parallel plates is studied using the method of reflections and the boundary integral method. A sample calculation was performed for the case of a sphere located 40% of the channel width from one of the walls. The walls induce crescent-shaped vortices comparatively near but not attached to the sphere, which travel with the sphere. The walls aslo induce a curious viscous lateral migration totally unlike that observed in Couette flow. In the calculation, the walls diminish the evasive motion of the fluid around the sphere, asymmetrically. That is, the motion on the side of the sphere nearest to a wall is comparatively flattened.
α transducin is present in blue-, green-, and red-sensitive cone photoreceptors in the human retina

Phototransduction in vertebrate rod and cone photoreceptor cells involves G protein-mediated light stimulation of cGMP hydrolysis. Enzymes of the cGMP hydrolysis cascades of rods and cones are products of different genes. Three different classes of cones in the human retina are maximally sensitive to either blue, green, or red light. Distinct opsin genes are expressed in each type of cone. The distribution of cone types in human retina was determined using anti-peptide antibodies that recognize specific amino acid sequences in green/red opsin and blue opsin. These antibodies together with an anti-peptide antibody against Tc alpha were used in double labeling experiments to demonstrate the presence of the Tc alpha peptide in all types of cones. cDNA clones corresponding to human rod and cone transducin alpha subunit (Tr alpha and Tc alpha) genes were isolated. Southern blot analyses of human genomic DNA suggest that there is only one rod T alpha gene but more than one cone T alpha gene. The multiple Tc alpha genes could be closely related genes or different Tc alpha alleles, or one could be a pseudogene.
Array-based sensing using nanoparticles: an alternative approach for cancer diagnostics.

Array-based sensing using nanoparticles (NPs) provides an attractive alternative to specific biomarker-focused strategies for cancer diagnosis. The physical and chemical properties of NPs provide both the recognition and transduction capabilities required for biosensing. Array-based sensors utilize a combined response from the interactions between sensors and analytes to generate a distinct pattern (fingerprint) for each analyte. These interactions can be the result of either the combination of multiple specific biomarker recognition (specific binding) or multiple selective binding responses, known as chemical nose sensing. The versatility of the latter array-based sensing using NPs can facilitate the development of new personalized diagnostic methodologies in cancer diagnostics, a necessary evolution in the current healthcare system to better provide personalized treatments. This review will describe the basic principle of array-based sensors, along with providing examples of both invasive and noninvasiv...
Integration of LIGA structures with CMOS circuitary

Successful direct integration of a mechanical structure fabricated by LIGA on a Si chip containing CMOS circuitry has been achieved in this work. A 1D cantilever accelerometer is chosen as a vehicle to demonstrate this integration process. The capacitive sensor element employs one electrode formed in the Si substrate during the integrated circuit fabrication. The other electrode is fabricated using the LIGA technique with sacrificial layer etching. Details of the fabrication process to achieve this integration are given. Need for careful control of stress in the deposited layers and achieving appropriate contrast in the X-ray mask are delineated.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Prostaglandin E2 Stimulates the β-Catenin/T Cell Factor-dependent Transcription in Colon Cancer

Cyclooxygenase and its derived prostaglandin E2 (PGE2) have been shown to stimulate the growth of cancer cells and promote tumor angiogenesis. Here, we show that PGE2 activated the β-catenin/T cell factor-dependent transcription in colon cancer cells through the cAMP/protein kinase A pathway. The expression of cyclin D1 and vascular endothelial growth factor was induced by PGE2 in LS-174T cells. Moreover, PGE2 and mutated β-catenin stimulated the transcription of cyclin D1 and vascular endothelial growth factor in a synergistic fashion. Mechanistically, PGE2 increased the phosphorylation of glycogen synthase kinase-3 and consequently accumulated β-catenin. In addition, PGE2 induced the expression of T cell factor-4 transcription factor, which formed transcriptionally active complex with β-catenin. In animal experiments, administration of 16,16-dimethyl PGE2 strongly increased the expression of cyclin D1 and vascular endothelial growth factor in APCmin/+ mouse polyps. Thus, our results provide a novel mechanism, suggesting that cyclooxygenase-2/PGE2 may exert pro-oncogenic actions through stimulating the β-catenin/T cell factor-mediated transcription, which plays critical roles in colorectal carcinogenesis.
A yeast replication origin consists of multiple copies of a small conserved sequence.

Abstract Autonomously replicating sequences (ARSs) of the yeast S. cerevisiae function as replication origins on plasmids and probably also on chromosomes. ARS function requires a copy of the ARS core consensus (5′-[A/T]TTTAT[A/G]TTT[A/T]-3′) and additional sequences 3′ to the T-rich strand of the consensus. Our analysis of an ARS from chromosome III, the C2G1 ARS, suggests that ARS function depends on the presence of an exact match to the core consensus and the presence of additional near matches in the 3′ flanking region. We have demonstrated that ARS function can be mediated by multiple matches to the core consensus by constructing synthetic ARS elements from oligonucleotides containing copies of the consensus sequence. We find that two copies of the core consensus are sufficient for ARS activity and that an artificial ARS as efficient as a natural chromosomal ARS can be constructed from multiple core consensus elements in a specific orientation.
Accidental exposure to sarin: vision effects

Two men were accidentally exposed to vapors of sarin, a cholinesterase inhibitor and extremely toxic nerve gas. Diagnosis was confirmed by depressed cholinesterase activity, and fixed extremely miotic pupils. No other signs or symptoms developed and neither man required treatment. Recovery to normal cholinesterase activity was gradual over a 90-day period. Pupillary reflexes were not detectable until 11 days after exposure; the miotic pupils dilated slowly over a 30–45 day-period. Eye pain and blurred vision did not occur; visual acuity and amplitude of accommodation were improved for several weeks. Other functions not affected significantly were intraocular pressure, visual fields, color vision, heterophorias, and vergences.
Abstract 2592: Vitamin E forms and 13′-carboxychromanol, a long-chain metabolite of α-tocopherol, induce cell death by interruptingde novosphingolipid synthesis in human cancer cells

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Studies have shown that vitamin E forms including gamma-tocopherol (≥T), delta-tocopherol (≥T) and especially gamma-tocotrienol (≥TE), a major form of vitamin E in palm oil, exhibited potent anticancer activities in various types of cancer cells. 13′-carboxychromanol (13′-COOH), a long-chain metabolite of αT, has recently been shown to have anti-inflammatory activities and appears to induce apoptosis in certain type of cancer cells. However, the molecular mechanisms of the anticancer effects are not understood. In the current study, we found that 13′-COOH inhibited the growth and induced death of human colon and pancreatic cancer cells in a time- and dose-dependent manner. In these activities, 13′-COOH was more potent than αTE, which is much stronger than αT and αT. Since we have previously shown that αTE and αT induce prostate cancer cell death by modulation of sphingolipid metabolism, we investigated whether αTE and 13′-COOH have effects on sphingolipids using liquid chromatography tandem mass spectrometry. Treatment of HCT116 cells with αTE or 13′-COOH significantly increased dihydroceramides and dihydrosphingosine, two sphingoid bases in de novo synthesis pathway of sphingolipids. In contrast, sphingomyelins and ceramides remained largely unchanged after treatment. This accumulation of intracellular dihydroceramides and no apparent change of sphingomyelins suggest potential inhibition of dihydroceramide desaturase (DEGS) enzyme by these compounds. Consistently, we found that αTE inhibited the DEGS activity in a time- and dose-dependent manner in an in situ assay, while it did not have any effect on DEGS expression. These results indicate that αTE and 13′-COOH interrupt de novo synthesis of sphingolipids, which play a role in regulating cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2592. doi:1538-7445.AM2012-2592
Interspecies modeling and prediction of human exenatide pharmacokinetics.

Purpose To develop a model-based approach for interspecies scaling of the preclinical pharmacokinetics of exenatide and to predict concentration-time profiles in humans.
Pulmonary function in adolescent idiopathic scoliosis relative to the surgical procedure

Background: The long-term pulmonary function of patients with adolescent idiopathic scoliosis undergoing surgical correction is uncertain. To our knowledge, no report has demonstrated the changes in pulmonary function five years or more following spinal arthrodesis with use of modern segmental spinal instrumentation techniques for the treatment of all types of adolescent idiopathic scoliosis in a similar adolescent population. Methods: One hundred and eighteen patients with adolescent idiopathic scoliosis undergoing surgical treatment at a single institution were evaluated with pulmonary function tests to assess the absolute and percent-predicted value of forced vital capacity and forced expiratory volume in one second at the preoperative examination and at regular intervals postoperatively. The patients were divided into four groups depending upon the surgical procedure: Group 1 comprised forty-nine patients who had posterior spinal arthrodesis with iliac crest bone graft; Group 2, forty-one patients who had posterior spinal arthrodesis with thoracoplasty; Group 3, sixteen patients who had open anterior spinal arthrodesis with a rib resection thoracotomy; and Group 4, twelve patients who had combined anterior and posterior spinal arthrodesis with a rib resection thoracotomy and iliac crest bone graft, respectively. Results: A comparison of absolute pulmonary function values from the preoperative and final follow-up evaluations demonstrated a significant (p < 0.0001) increase in both the forced vital capacity and the forced expiratory volume in one second for Group 1, whereas no change was seen in those values for Groups 2, 3, and 4. A comparison of the changes in the percent-predicted pulmonary function values demonstrated significant (p < 0.05) decreases in forced vital capacity and forced expiratory volume in one second for Groups 2, 3, and 4, except for the latter value for Group 4, whereas Group 1 had no change. Conclusions: Patients who have had any type of chest cage disruption during the surgical treatment of adolescent idiopathic scoliosis demonstrate no change in the absolute value and a significant decline in the percent-predicted value of pulmonary functions at five years following surgery. Chest cage preservation is recommended to maximize both absolute and percent-predicted pulmonary function values after surgical treatment of adolescent idiopathic scoliosis. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.
Topical Carbonic Anhydrase Inhibitors III: Optimization Model for Corneal Penetration of Ethoxzolamide Analogues

An analogue series representing modification to the benzene ring of ethoxzolamide has been evaluated for solubility, pKa, partitioning, and permeability across excised rabbit corneas. These physical parameters were correlated to Hammett σ (para) and/or Hansch π parameter values for each compound. From these correlations, a mathematical model was developed relating corneal permeability to molecular modifications of ethoxzolamide. A three‐dimensional plot of maximium attainable penetration rate versus σ (para) and π yielded an optimal range of π and σ values from which an optimally penetrating analogue could be designed.
Coevolution of form and function in the design of micro air vehicles

This paper discusses approaches to cooperative coevolution of for and function for autonomous vehicles, specifically evolving morphology and control for an autonomous micro air vehicle (MAV). The evolution of a sensor suite with minimal size, weight, and power requirements, and reactive strategies for collision-free navigation for the simulated MAV is described. Results are presented for several different coevolutionary approaches to evolution of form and junction (single- and multiple-species models) and for two different control architectures (a rulebase controller based on the SAMUEL learning system and a neural network controller implemented and evolved using ECkit).
Experimentally Determined Overall Burning Rates of Coal Chars

Abstract Abstract-Simultaneous measurements of the size, temperature, and velocity of single pulverized-coal char particles are used to determine the overall burning rates of the chars flowing in hot. oxidizing gaseous environments. The single film model of a burning carbon particle is employed with CO as the sole heterogeneous reaction product. Arrhenius parameters which describe the chemical reaction rate coefficients are derived for the chars of a hvb-biturninous coal from Missouri, a North Dakota lignite and a high-swelling, bituminous coal from Kentucky. Gaseous environments in the temperature range 14S0 to 1550 K, having one, three and six mole-percent oxygen were employed. The measurements indicate that in the three and six mole-percent oxygen environments, the temperatures of particles in the size range 70 to 150 &#x1d6cd;m exceed the local gas temperatures by as much as 150 K. The results suggest that at high particle temperatures, the chars of the coals burn in a regime in which the overall particle bur...
Genes, pollutants and human diseases.

The use of traditional Western concepts of disease (i.e. the ‘germ’ theory) has guided the use of scientific knowledge and technologies in the Control of acute infectious diseases (Gori & Peters, 1975; Trosko & Chang, 1978c). The intervention of all sorts of technologies has prolonged the life expectancy, allowing more people to reach the limit of what appears to be a rather fixed life-span (Hayflick, 1976). At the same time, human beings have used technologies to alter out dependence on the natural enviroment We intervene on many levels to minimize threats to our dependence on natural forces for food (e.g. agricultural technology, food additives), for water (e.g. wells or dams), for health (e.g. instituting sanitary measures or using drugs), for protection against the elements (e.g. wearing clothes, building homes with heaters and air conditioners) and for pleasure (e.g. snowmobiles, etc.). It is now extremely clear that much of the ‘effluents of our technological affluence’ can be harmful to living systems.