cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3208: Semaphorin 3F suppresses telomerase activity

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Objectives: Telomerase is a ribonucleoprotein that is active in more than 90% of human tumors, including ovarian cancers. We have previously demonstrated that vascular endothelial growth factor (VEGF) stimulates telomerase activity in ovarian cancer cell lines through cellular VEGF receptors and the ERK1/2 pathway targeting Sp1 sites within the hTERT promoter. Since semaphorin 3F (S3F), a proposed tumor suppressor, has been shown to antagonize VEGF, the purpose of this study was to determine whether S3F inhibits telomerase Methods: Telomerase-positive ovarian cancer cell lines (OV2008, C-13, SW626) and telomerase-negative non-tumorigenic, SV-40 large-T antigen-transfected human ovarian surface epithelium (HOSE) cell lines were evaluated for endogenous RNA and protein expression of S3F, VEGF, and their shared receptors. Cultured cells were either treated with recombinant S3F protein or transiently transfected with cDNA to over-express S3F. Conversely, these cells were transiently transfected with siRNA targeting S3F ± specific receptor inhibitors. RT-PCR and western blot confirmed S3F over-expression, knock-down of S3F, or inhibition of receptors. Telomerase activity was measured by telomerase PCR-ELISA, while RT-PCR and western immunoblotting were utilized to detect S3F as well as to explore the signaling pathway involved in S3F-mediated telomerase regulation. Results: Telomerase activity was suppressed in ovarian cancer cell lines following treatment with S3F recombinant protein or S3F over-expression by transient transfection. Furthermore, siRNAs targeting S3F and NP-2 or treatment with the VEGF receptor inhibitor, CBO-P11, abrogated S3F mediated telomerase inhibition. Over-expression of S3F resulted in up-regulation of phosphorylation of Erk1/2. Conclusions: These data suggest that telomerase is a novel molecular target of S3F. Since, angiogenic and angiostatic factors play an important role in ovarian cancer tumorigenesis, S3F-mediated inhibition of telomerase represents a potential novel target for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3208.
It Is Time! Accelerating the Use of Child Health Information Systems to Improve Child Health

Articles in this issue show clearly the enormous impact that the use of health information technology can have on the quality of health care for children. However, they also point out the challenges that need to be overcome to realize fully the potential of health information technology to improve the quality and efficiency of health care.
Novel implementations of dual- and triple-band filters on double-sided substrates

A new implementation technique of dual- and triple-band filters is presented in this paper. The filters are realized by utilizing a double-sided substrate with a common ground plane. The coupling between the non-adjacent resonators of the filters is realized through coupling slots in the common ground plane of the double-sided substrate. Several dual- and triple-band filters are fabricated and tested demonstrating the desired characteristics.
Rapid microbial metabolism of non-protein amino acids in the sea

The non-protein amino acids, β-alanine and γ-aminobutyric acid, frequently dominate the amino acid composition of deep-sea sediments. This accumulation is most likely due to the slower decomposition of non-protein amino acids by microorganisms or to the preferential adsorption of non-protein amino acids by clay minerals. We investigated relative rates of heterotrophic uptake of alanine, β-ala, and γ-aba in sea water to see if there were different rates of microbial assimilation and respiration between these protein and non-protein amino acids. Heterotrophic uptake was rapid for all three amino acids with turnover times of hours in productive coastal waters and days in more oligotrophic open-ocean waters. Uptake of the non-protein amino acids was significantly slower than uptake of alanine, particularly in anoxic waters. However, the difference in uptake rates is probably not great enough to cause significant preferential accumulation of non-protein amino acids.
Increased depth of field and stereo pairs of fluorescence micrographs via inverse filtering and maximum-likelihood estimation

SUMMARY Image processing methods are presented for effectively increasing the depth of field and for generating stereo pairs of fluorescence micrographs from a conventional optical microscope. In developing these methods the slice theorem of computed tomography is used. In this way the image reconstruction problem is reduced to one of processing only two-dimensional arrays rather than three-dimensional arrays and the classical difficult problem of restoring missing Fourier components within the missing cone region is circumvented. Two different approaches to such processing are presented. One approach is based on inverse filtering. Another approach is based on previous development of iterative image restoration algorithms for quantum-limited incoherent imagery, founded on maximum-likelihood estimation. Limited experimentation with real micrographs shows that both approaches work well. Some preliminary comparisons are made between the different variations of the methods tested, which point out the advantages and present limitations. Both methods can be implemented on IBM-AT-compatible computers with relatively fast execution times. Advantages that these methods have over confocal microscopy are (i) the optical and computing equipment required is less expensive, and (ii) a conventional microscope when set up properly can have much better light sensitivity than a confocal microscope.
A new method of quench monitoring in liquid scintillation counting: The H number concept

The quench level of different liquid scintillation counting samples is measured by comparison of the responses (pulse heights) produced by the same energy electrons in each sample. The electrons utilized in the measurements are those of the maximum energy (Emax) which are produced by the single Compton scattering process for the same energy gamma-rays in each sample. The relation of the Emax response produced in any sample is related to the Emax response produced in an unquenched, sealed standard. The relation, difference in response on a logarithm response scale, is defined as the “H Number,” H#. The H# is related to the counting efficiency of the desired radionuclide by measurement of a set of standards of known amounts of the radionuclide and different amounts of quench (standard quench curve). This report presents the theory of the H# concept. Several of the unique features of the H# method are discussed. Quench curves based upon the H# are compared to other previously used methods of quench monitoring.
Traumatic neuronal injury in vitro is attenuated by NMDA antagonists

Pure traumatic neuronal injury was modeled in dispersed neocortical cell cultures derived from fetal mice. A plastic stylet was used to tear the neuronal and glial cell layer; medium oxygen content, pH, and glucose remained unchanged. Adjacent to this local disruption, many neurons developed acute swelling and went on to degenerate over the next day, but glia were relatively spared. If the same mechanical insult was delivered in the presence of the N-methyl-D-aspartate (NMDA) antagonists dextrorphan or D-2-amino-5-phosphonovalerate, resultant neuronal degeneration was markedly reduced. The protective effect of these NMDA antagonists was concentration-dependent between 1 and 100 microM, with EC50 near 10 microM for both compounds. Present findings suggest that endogenous excitatory amino acids may participate significantly in the propagation of central neuronal cell loss in response to a purely mechanical insult.
Tracking the Time Course of Spoken Word Recognition Using Eye Movements: Evidence for Continuous Mapping Models

Abstract Eye movements to pictures of four objects on a screen were monitored as participants followed a spoken instruction to move one of the objects, e.g., “Pick up the beaker; now put it below the diamond” (Experiment 1) or heard progressively larger gates and tried to identify the referent (Experiment 2). The distractor objects included a cohort competitor with a name that began with the same onset and vowel as the name of the target object (e.g.,beetle), a rhyme competitor (e.g.speaker), and an unrelated competitor (e.g.,carriage). In Experiment 1, there was clear evidence for both cohort and rhyme activation as predicted by continuous mapping models such as TRACE (McClelland and Elman, 1986) and Shortlist (Norris, 1994). Additionally, the time course and probabilities of eye movements closely corresponded to response probabilities derived from TRACE simulations using the Luce choice rule (Luce, 1959). In the gating task, which emphasizes word-initial information, there was clear evidence for multiple activation of cohort members, as measured by judgments and eye movements, but no suggestion of rhyme effects. Given that the same sets of pictures were present during the gating task as in Experiment 1, we conclude that the rhyme effects in Experiment 1 were not an artifact of using a small set of visible alternatives.
An examination of primary and secondary dissociation pathways of trifluoromethanol: Identification of plausible routes leading to the formation of hydrogen fluoride

Abstract Primary and secondary decomposition pathways of trifluoromethanol have been examined with the aim of identifying reactive routes which lead to the formation of hydrogen fluoride. Geometries determined at the UHF/6-31G(d) level of theory and single point energies obtained with PMP4(SDQ)//UHF/6-31G(d) wavefunctions predict that the 1,2-elimination of hydrogen fluoride is thermodynamically and kinetically the most favored route. All other processes, including primary and secondary pathways, require energies in excess of 50 kcal mol −1 above the 1,2-HF elimination route in order to occur.
Coordination of adenosylmethionine to a unique iron site of the [4Fe-4S] of pyruvate formate-lyase activating enzyme: a Mössbauer spectroscopic study.

Pyruvate formate-lyase activating enzyme (PFL-AE) generates the catalytically essential glycyl radical of PFL. It is a member of the so-called "radical-SAM superfamily" of enzymes that use a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet or SAM) to catalyze diverse radical-mediated reactions. Evidence suggests that this class of enzymes operate by common initial steps involving the generation of an AdoMet-derived adenosyl radical intermediate, of which the mechanism remains unresolved. The three-cysteine CX3CX2C cluster-binding motif common to all members of this superfamily suggests a unique Fe site in the [4Fe-4S] cluster, which presumably interacts with AdoMet to effect the reductive cleavage and radical generation. Here we employ a dual-iron-isotope (56Fe/57Fe) approach to demonstrate the existence of a unique Fe site in the [4Fe-4S] cluster of PFL-AE by Mossbauer spectroscopy. Coordination of AdoMet to this unique Fe site was made evident by the observation of a substantial increase in the isomer shift (delta) of the Mossbauer spectrum associated with the unique Fe site: delta = 0.42 mm/s in the absence of AdoMet increases to delta = 0.72 mm/s in the presence of AdoMet. Further, the Mossbauer data show that the binding of AdoMet to the unique Fe site occurs in the [4Fe-4S]2+ state, prior to the injection of the reducing equivalent required for catalysis. This observation indicates that AdoMet coordination is a necessary prerequisite to adenosyl radical generation.
Impact Ionization in Semiconducting Single Wall Carbon Nanotubes

We have experimentally observed and modeled a second-order transport mechanism near breakdown in large-diameter (small-gap) semiconducting SWNTs. We determine impact ionization to be the primary cause of the up-kick in current. Subsequent simulations taking impact ionization into account provide a theoretical match to our experimentally observed current tail.
Sequential analysis of visual habituation in preschool children

The study breaks down the data from a preschool (mean age of students, 63 months) visual habituation experiment using a second-by-second analysis of the entire process, including fixation time and onsets for habituation and recovery trials and for each intertrial interval. The results parallel those suggested by Cohen, DeLoach, and Rissman (Child Development, 1975, 46, 611–617), for infants and are described using a two-process model of visual attention.
Polymerization in a Reverse Micelle Nanoreactor: Preparation of Processable Poly(p-phenylenevinylene) with Controlled Conjugation Length

We show that a nanoscale polymerization reaction within the confinement of a reverse micellar cavity yields products with controlled conjugation lengths and, thus, controlled band gaps for applications to electronics and photonics. In addition, control of the physical size (length) of the polymer provides the prospects of monodispersity, improved processability, and preparation of nanocomposites. This novel approach has been successfully applied to produce controlled chain length poly(p-phenylenevinylene) (PPV), a polymer that has drawn considerable attention in recent years for its electroluminescence, nonlinear optical, and lasing properties.
The Perceived Effectiveness of Selected Programs and Sources with Respect to Preventing the Use of Dangerous Drugs.

The purpose of this investigation was to determine the perceived effectiveness of selected types of programs and resource people which may be utilized in drug abuse education endeavors. A total of 195 university students were included in this study with an approximately equal representation of male and female students. One group received a drug education course and the other served as a control. Each student was asked to rate the perceived effectiveness of selected types of programs and sources with respect to “preventing or stopping the use of dangerous drugs.” Similar findings were evidenced for both groups. Results indicated that certain drug abuse program and individuals were perceived as being more effective than others.
Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

The nicotinic acetylcholine receptors are prototypic ionotropic receptors that mediate fast synaptic transmission. However, also non-excitable cells, and particularly the tegumental cells that line external and internal body surfaces, express acetylcholine receptors of neuronal type sensitive to nicotine. Bronchial epithelial cells, endothelial cells of blood vessels and skin keratinocytes express neuronal nicotinic receptors composed of α3, α5, β2 and β4 subunits, similar to those expressed in sympathetic ganglia, and neuronal nicotinic receptors composed of α7 subunits. Neuronal nicotinic receptors in tegumental cells are involved in modulating cell shape and motility, and therefore in maintaining the integrity of the surfaces lined by those cells. Neuronal nicotinic receptors in non-neuronal tissues may modulate other functions, including cell proliferation and differentiation. Acetylcholine is synthesized, secreted and degraded by a variety of cells, including the tegumental cells that express neuronal nicotinic receptors. Thus, acetylcholine may function as a local “hormone” that is able to modulate cell functions that require fast adaptation to new conditions. The presence of neuronal nicotinic receptors sensitive to nicotine in tissues known to be involved in tobacco toxicity, like bronchi and blood vessels, raises the possibility that they mediate some of the toxic effects of smoking.
A unified method for phase shifter computation

Phase shifters are used to shift the bit sequences produced by the successive stages of a built-in test pattern generator (TPG) based on a linear finite state machine (LFSM) by a specified amount (phase shift) relative to the characteristic sequence. An upper bound on the number of taps to be used for each phase shifter and a lower bound on the phase-shift value between successive stages of the TPG mechanism are the general parameters of the problem. Methods to design such phase shifters have been given in the past separately for Type-1 LFSRs, Type-2 LFSRs, and three-neighborhood cellular automata. In this article, we show how phase shifters can be synthesized uniformly and efficiently for any LFSM, including the aforementioned ones. We demonstrate the method by showing how to obtain phase shifters for two-dimensional cellular automata and for ring generators.
Hormone ontogeny in the ovine fetus. XI. The Serotoninergic regulation of growth hormone and prolactin secretion.

To investigate the development of serotonin-mediated GH and PRL release in the ovine fetus and neoriate, we administered 5-hydroxytryptophan (5-HTP; 20 mg/kg, iv) to 11 chronically catheterized fetuses (84–134 days old; term gestation, 147 days) and 10 infant lambs. In fetuses less than 110 days gestation (n = 4), the concentration of plasma GH rose from 101 ± 9 to 334 ± 31 ng/ml after 5-HTP (P < 0.001). The response in fetuses older than 110 days was less (P < 0.01); the mean concentration of GH rose from 127 ± 26 to 172 ± 34 ng/ml (P < 0.01). In infant lambs with lower basal GH concentrations, a GH rise comparable to that in late gestation was observed (from 6.5 ± 0.6 to 45 ± 12 ng/ml). There was a negative correlation between the incremental GH response to 5-HTP and postconceptual age (P < 0.01). 5-HTP failed to induce a PRL response in four fetuses less than 110 days old; the mean basal concentration of PRL was 10.7 ng/ml in this group. In older fetuses (121–134 days old), PRL rose from 40 ± 8 to 69 ±...
Age and growth rate determinations for the Atlantic surf clam Spisula solidissima (Bivalvia: Mactracea), based on internal growth lines in shell cross-sections

Marked and recovered surf clams, Spisula solidissima Dillwyn, from Virginia (USA) deposited one internal growth line during a period of 11/2 years, probably in response to spawning during late summer. We have used these annual growth lines to make growth curves for two samples of New Jersey (USA) clams, one from inshore (1.8 km from shore, 15 m deep), the other from offshore (17.5 km from shore, 28 m deep) waters. The offshore and inshore clams grow at approximately the same rate until Age 3 years, after which time the growth rates differ, as does the ultimate lifespan; the offshore clams grow more rapidly and attain a greater age — up to 31 years. Comparison of our growth curves with other published curves revealed a close correspondence to a curve which was based on a study of growth over a 5-year period. Curves based on external growth lines probably underestimate growth rate in early life and overestimate it in later years.
The role of multiparticle-adatom interactions on the sintering of supported metal catalysts

Abstract Sintering of supported metal particles involves the transfer of single atoms (adatoms) and the movement of crystallites on the substrate. The present work considers the coupled role of all crystallites in determining the diffusion of adatoms on the two-dimensional surface, and the consequent growth and dissolution of crystallites. A decomposition-summation procedure is used. The results of this approach can be compared to those from the mean-field approach, where multiparticle interactions are neglected. The present approach is particularly valid when metal crystallites are found in clumps on the surface i.e., at high local metal loadings. The particle size distributions that result when multiparticle interactions are considered in the sintering analysis depend upon the metal loading, and are significantly flatter and broader than those of the “asymptotic” mean-field analysis. Further, the average particle size calculated here increases with metal loading, in contrast to that from the “asymptotic” mean-field analysis. Finally, the relationship between the time of sintering and the average particle size calculated here changes from concave to convex at higher metal loadings.
Analysis of Non-Dispatchable Options in the Generation Expansion Plan

The analysis of Non-Dispatchable Technology (NDT) options in the expansion plan requires accurate, computationally efficient and flexible modeling of generation uncertainties and relevant statistical interdependencies (correlations). The implementation of a suitable methodology and computational results including sesitivity analysis on the capital cost and "hardware" reliability of the NDT option are presented and analyzed. The methodology has been implemented in the Electric Generation Expansion Analysis System (EGEAS) software package developed for EPRI by the Massachusetts Institute of Technology.
The subspace projected approximate matrix (SPAM) modification of the Davidson method

Abstract A modification of the iterative matrix diagonalization method of Davidson is presented that is applicable to the symmetric eigenvalue problem. This method is based on subspace projections of a sequence of one or more approximate matrices. The purpose of these approximate matrices is to improve the efficiency of the solution of the desired eigenpairs by reducing the number of matrix–vector products that must be computed with the exact matrix. Several applications are presented. These are chosen to show the range of applicability of the method, the convergence behavior for a wide range of matrix types, and also the wide range of approaches that may be employed to generate approximate matrices.
The Association Between Self-Control and Hoarding: A Case Report

Abstract The capacity to exert control over one's behavior is known as self-control, and this ability to self-regulate is a necessary component for directing personal behavior toward achieving a specific goal. Baumeister and colleagues have suggested that self-control operates within a resource model such that an individual may strengthen this resource through directed practice. Hoarding is one syndrome wherein self-control may play a substantial role. Within a translational research framework, two separate case studies sought to determine if practicing self-control in a non-hoarding-related domain might have an impact on an individual's hoarding symptoms and their readiness for treatment. Two individuals diagnosed with hoarding were enrolled in a self-control practice condition. Both self-control levels and hoarding symptoms were measured at pre– and post–time points using self-report and behavioral indices. Findings in support of a favorable effect of self-control on mitigating behavioral hoarding symptoms were mixed, with 1 patient experiencing marked improvement in symptoms and the other not. We also found that self-control practice was associated with both increased motivation for treatment and overall level of self-awareness. The implications of self-control for hoarding are discussed from a disease-reduction and prevention standpoint, along with the role self-control might play within more traditional cognitive behavioral interventions.
Practices Regarding Reporting of Reliability Coefficients: A Review of Three Journals

Practices regarding the reporting of reliability coefficients in 3 journals from 1990 to 1997 were examined. Given that scores, not tests, are reliable or unreliable, particular attention was paid to the provision of reliability coefficients computed for the data actually being analyzed in substantive studies. One third of the articles reviewed made no mention of reliability. Almost 36% of the articles provided reliability coefficients for the data being analyzed. Examples of good reporting practices are provided. In 2 of the 3 journals reviewed, there was little change in the frequency and style of reliability reporting in the period covered. The authors suggest a modification in editorial journal policies to bring about a change in reliability-coefficient reporting practices.
The future of phase-change semiconductor memory devices

Phase-change memory (PCM) has recently been under active development by a number of semiconductor manufacturing companies and research laboratories. This development has been accelerated both by the rapidly growing market for nonvolatile memory in cellular phones and other types of portable electronic equipment and by the realization that Flash memory, the currently dominant nonvolatile memory technology, will face serious challenges as it scales in the future to smaller and smaller dimensions. PCM nonvolatile memory technology has shown scaling, speed, and endurance characteristics which could allow it to replace Flash memory in future applications and, perhaps in time, DRAM memory as well. Commercial introduction of PCM memory chips which can replace NOR Flash is anticipated to begin this year. The performance and scaling advantages of PCM are a direct consequence of the memory cell device physics and fundamental properties of the phase-change alloys and these will be reviewed in light of future memory requirements and competition from other emerging memory technologies.
Infantile panthalamic infarct with a striking sonographic finding: the "bright thalamus".

A “bright thalamus” is not uncommonly observed in cranial sonograms of asphyxiated neonates, but not those of older infants. Three infants, aged 9–14 months, developed acute onset of seizures and disturbance of consciousness after a minor prodromal illness. Bilateral thalamic infarcts were demonstrated by ultrasonography and CT. One patient expired from causes not directly related to the infarcts; the other two survived with severe neurological sequelae.
Expression of recombinant pro-neuropeptide Y, proopiomelanocortin, and proenkephalin: relative processing by 'prohormone thiol protease' (PTP).

The preference of the ‘prohormone thiol protease’ (PTP), a candidate prohormone processing enzyme, for different peptide precursors was assessed in vitro with recombinant prohormones near estimated in vivo levels. Pro-neuropeptide Y (pro-NPY), prooplomelanocortin (POMC), and proenkephalin (PE) were expressed at high levels in E. coli. Purification of prohormones utilized a combination of DEAE-Sepharose, Mono Q, and preparative electrophoresis. PTP cleaved PE most readily, and also cleaved pro-NPY. The processing of POMC by PTP was minimal. These results demonstrate PTP's preference for certain prohormone substrates.
Conduction-band plasmons in cluster-type compounds: Application to fullerides and quantum-dot arrays.

We analyze collective excitations of carriers in three- and two-dimensional crystals made up of cluster-type units (fullerenes, quantum dots, etc.). This class of compounds is unique in that the electrons are essentially confined to the individual clusters, while the latter are both large in size and close packed. We derive a general expression for the dispersion law of conduction-band plasmons, and apply it to alkali-metal-doped fullerides and quantum-dot arrays. We find that the dispersion relation is modified from the case of a homogeneous electron gas: it becomes measurably steeper and acquires a downward slope. This change is due to the appearance of a term which is determined by the density distribution of electrons within a unit cluster. Related electron-energy-loss spectroscopic data on the doped fullerides are discussed.
Mobilization of Fat Body Glycogen by an Extract of Corpus Cardiacum

HUMORAL involvement in the carbohydrate metabolism of Periplaneta americana (L.) has been reported by Steele1, who demonstrated a 150 per cent increase in blood trehalose and a drop in blood glucose following injection of an aqueous extract of the corpus cardiacum. The work recorded here, conducted as part of an overall investigation of the regulation of sugar utilization in the South American cockroach, Blaberus discoidalis (Serville), confirms the rise in trehalose, but reveals also a significant increase in blood glucose and a concomitant decrease in fat body glycogen.
Microorganisms associated with the spider mite predator Metaseiulus (= Typhlodromus) occidentalis: Electron microscope observations

Abstract Two morphologically distinct forms of microorganisms were observed with the electron microscope in the tissues of the phytoseiid mite Metaseiulus (= Typhlodromus) occidentalis . The forms were distinguished on the basis of cell wall structure and cytoplasmic inclusions. One microorganism, designated type A, was observed in all mites examined. The second microorganism, type B, was observed in approximately two-thirds of the mites examined. If present, type B microorganisms occurred in all ovaries and egges, suggesting that transovarial transmission may take place. In some mites large numbers of type B microorganisms were observed within Malpighian tubule lumens and in a rectal plug. Whether this population was primarily or secondarily associated with a pathology is discussed.
Does the Provision of Nonaudit Services Affect Investor Perceptions of Auditor Independence

A number of recent studies examine whether the joint provision of audit and nonaudit services (NAS) impairs auditor independence, and yield mixed results. We examine whether investors perceive auditor independence as being impaired when auditors supply nonaudit services, by investigating the association between fee‐based measures of nonaudit service purchases and the earnings response coefficient (ERC). We find that the nonaudit fee ratio and the level of nonaudit fees were negatively associated with ERCs in 2001. When we use unexpected fees (a measure of over‐ or underpayment of nonaudit fees), we find a negative association between NAS purchases and ERC, but this occurs mainly in the second and third quarters following the release of the proxy. Further investigation reveals that the quarterly differences may be driven by the increasing flow of information (i.e., the first‐time disclosures of fees and media analyses of these disclosures) that became available to investors during our sample period. We spe...
Cosmic Implications of NXY-059

The SAINT studies on NXY-0591,2 have reinvigorated debate over the momentous issues of neuroprotection and the development of novel stroke therapeutics. Some may argue there is little new ground that NXY-059 has unearthed and, in fact, the clinical trials merely confirm that as a strategy, neuroprotection has not been shown to be effective. Editorials in high-profile journals have sent out the clarion call to terminate research on neuroprotection given decades of work, which has uniformly led to failure after failure in clinical studies.3 These sentiments are premature and ignore studies showing that hypothermia improves outcome in patients after cardiac arrest, a major cause of global cerebral ischemia.4,5 Proof for the neuroprotection concept has therefore already been established. Despite decades of neutral clinical trials, there still remains optimism among the stroke academic community. A majority of university-affiliated stroke neurologists in the United States in a recent survey still believe neuroprotection is a viable therapeutic strategy, although admittedly, that survey was conducted between the SAINT I and SAINT II publications.6 However, the question whether neuroprotection will ever work in stroke has been overshadowed by the larger issue of whether animal studies, which serve as the foundation for the development of stroke therapeutics, are even relevant to our patients with acute stroke. In the discussion section of the SAINT II article, the authors write, “it is possible that the animal models of acute focal infarction are not relevant to the patient population; they certainly are insufficient to guarantee a positive clinical-trial result.” Have all prior neuroprotective agents failed in clinical studies because rodent stroke is not relevant to human stroke? This is a key question. Substantial reductions in infarct size in rodents with stroke treated with various types of purported neuroprotective agents would seem to support this view. There …
A multiscale model for dilute turbulent gas-particle flows based on the equilibration of energy concept

The objective of this study is to improve Eulerian-Eulerian models of particle-laden turbulent flow. We begin by understanding the behavior of two existing models—one proposed by Simonin [von Karman Institute of Fluid Dynamics Lecture Series, 1996], and the other by Ahmadi [Int. J. Multiphase Flow 16, 323 (1990)]—in the limiting case of statistically homogeneous particle-laden turbulent flow. The decay of particle-phase and fluid-phase turbulent kinetic energy (TKE) is compared with direct numerical simulation results. Even this simple flow poses a significant challenge to current models, which have difficulty reproducing important physical phenomena such as the variation of turbulent kinetic energy decay with increasing particle Stokes number. The model for the interphase TKE transfer time scale is identified as one source of this difficulty. A new model for the interphase transfer time scale is proposed that accounts for the interaction of particles with a range of fluid turbulence scales. A new multiph...
Continuous fixed bed ligand exchange: The shrinking‐core model

Etude experimentale et modelisation du processus suivant : afin d'eliminer l'ammoniac ou la butylamine de l'eau dans le reacteur, on utilise un ion complexant, ici le cuivre (II), fixe sur une resine echangeuse d'ion. Determination des courbes de rupture pour les deux produits cites plus haut
Transcriptional modulation of TCR, Notch and Wnt signaling pathways in SEB Anergized CD4+ T cells

Gene expression changes in CD4 + Vbeta8+ T cells energized by in vivo exposure to staphylococcal enterotoxin B (SEB) bacterial superantigen compared to CD4 + Vbeta8+ non-energic T cells were assessed using DNA microarrays containing 5184 murine complementary DNAs. Anergy in splenic T cells of SEB-immunized BALB/c mice was verified by dramatically reduced proliferative capacity and an 8 x overexpression of GRAIL mRNA in CD4 + Vbeta8+ T cells taken from mice 7 days after injection. At an Associative t-test threshold of P<0.0005, 96 genes were overexpressed or detected only in anergic T cells, while 256 genes were suppressed or not detected in anergic T cells. Six of eight differential expressions tested using real-time quantitative PCR were validated. Message for B-Raf was detected only in non-anergic cells, while expression of the TCR signaling modulator Slap (Src-like adapter protein) and the TCR zeta-chain specific phosphatase Ptpn3 was enhanced. Modulation of multiple genes suggests downregulation of Wnt/beta-catenin signaling and enhanced Notch signaling in the anergic cells. Consistent with previous reports in a non-superantigen in vivo anergy model, mRNA for CD18 and the transcription factor Satb1 (special AT-rich-binding protein 1) was increased in SEB-energized T cells. This is the first report of global transcriptional changes in CD4+ T cells made anergic by superantigen exposure.
Prediction of Local Entropy Generation in Turbulent Combustion Systems

Analysis of local entropy generation or exergy destruction is an effective means to investigate sources of efficiency loss to optimize the performance of energy and combustion systems. The local entropy production is predicted using large eddy simulation of turbulent reacting flows. The unclosed entropy generation effects are accounted for by a novel methodology developed based on the filtered density function to embed the transport of entropy. Simulations are conducted of turbulent flames and predictions are validated via experimental data. Sources of irreversibility in turbulent combustion including viscous dissipation, heat conduction, mass diffusion and chemical reaction are predicted and analyzed. The influence of various operating parameters on local entropy generation and the exergetic efficiency of the combustion system is studied.© 2013 ASME
Brownian ratchets and the photoalignment of liquid crystals

Molecular motors play key roles in areas ranging from biological transport to emerging nanotechnology. They produce current as a result of transfer of energy but not of momentum from a source; many molecular motor scenarios are based on the translational Brownian ratchet mechanism. Here we consider the mechanism of photoalignment of liquid crystals both in the bulk and at the surface by a photosensitive alignment layer. We show that the photoalignment is due to an orientational ratchet mechanism, where the azo-dye molecules, functionalized into a polymer alignment layer, when irradiated by polarized light act as the rotors of Brownian motors which reorient the bulk liquid crystal against an elastic restoring torque. Results of this photoalignment experiment can be obtained directly from a remote experiment set up at the Liquid Crystal Institute, via the WWW. In addition to experimental results, we present a detailed Fokker-Planck description of this system. We discuss the implementation and the results of numerical simulations, and compare these with the experimentally observed dynamics.
Quenched chiral perturbation theory for heavy-light mesons.

We formulate quenched chiral perturbation theory for heavy-light mesons coupled to pions, and calculate the one-loop chiral logarithmic corrections to {ital f}{sub {ital B}}, {ital f}{sub {ital B}{sub {ital s}}}, {ital B}{sub {ital B}}, and {ital B}{sub {ital B}{sub {ital s}}}. We also calculate these corrections for {open_quote}{open_quote}partially quenched{close_quote}{close_quote} theories. In both theories, the chiral logarithms diverge in the chiral limit, indicating that (partially) quenched theories should not be used to study this limit. Comparing the chiral logarithms to those in QCD, we estimate the errors caused by (partial) quenching. By forming suitable ratios, we can reduce the uncertainties in our estimates. {copyright} {ital 1996 The American Physical Society.}
12: Cardiac storage with a perfusion device prevents tissue lactate accumulation

Purpose: Continuous perfusion devices may improve ischemic tolerance and extend preservation times. Initial clinical trials of these devices will likely involve standard preservation intervals. This study examined the effects of continuous perfusion in a large animal heart transplant model over a clinically relevant storage time. Methods and Materials: Hearts in adult dogs were instrumented with sonomicrometry crystals and a left ventricular (LV) micromanometer and LV function was quantified by the preload-recruitable stroke work (PRSW) relationship. Hearts were arrested with Celsior solution supplemented with 5 mM glucose, removed, and randomized to (A) storage in this solution in an ice chest (n 6) or (B) continuous perfusion with an identical solution at 10ml/100g/min in a perfusion device (n 6). After 4 h storage, samples of left atrium were frozen and later analyzed by magnetic resonance spectroscopy. Hearts were transplanted into recipient dogs and reperfused for 6 h, and function was measured. After 6 h, LV water content and serum CK-MB levels were measured. Results: LV function was similar at baseline in both the perfused and static-stored organs (PRSW: 50.4 5.9 vs 51.0 1.9 mmHg, mean SEM, respectively; p 0.64) and remained similar after 6 h reperfusion (40.4 6.4 vs 39.6 10.8 mmHg; p 0.62). Serum CK-MB levels after 6 h of reperfusion were similar (4.0 1.1 vs 6.9 2.4 ng/ml, p 0.30) in the perfused and static preserved organs. LV water content was not increased in the perfusion preservation group compared to routine storage (78.3 0.5% vs 78.3 0.2%; p 1.0). However, tissue collected at end-storage had significantly higher lactate content in the static storage group (expressed as lactate:alanine ratio; 0.6 0.4 vs 4.0 0.5; p 0.01). Conclusions: Continuous perfusion of donor hearts nearly eliminates tissue lactate accumulation without increasing myocardial edema. This may imply maintenance of oxidative metabolism or washout of anaerobic by-products during storage. Perfusion preservation may have advantages for heart preservation even over short storage intervals. I have received research support from Organ Transport Systems, the manufacturer of the perfusion device used in these studies; Organ Transport Systems, Inc.
Functional characteristics of in vitro generated macrophages: a transient refractory state precedes reinducibility of a spatially restricted, possibly contact-dependent, cytostatic mechanism.

Abstract Adherent layers of macrophages (Mφ-c) generated in vitro from splenic precursors previously have been shown to inhibit proliferation of normal and neoplastic cells by mechanisms that do not involve the secretion of significant quantities of prostaglandins, peroxides, or proteases. In the current report, it is demonstrated that the effective range of the cytostatic effect of adherent Mφ-c is so low that cytostasis can be circumvented by preventing the target cells from settling to the adherent layer by incubating the cultures of targets and Mφ-c on a rocking platform. Despite the paucity of production of inhibitory mediators, the Mφ-c do produce sufficient IL-1 to restore IL-2 production capacity to macrophage-depleted lymphocyte populations. The cytostatic activity of the Mφ-c is an inducible event and remains for several days in the continuous presence of mitogen-activated lymphocytes or LPS + lymphokines. Once the activators are removed the cytostatic activity rapidly declines, reaching background levels in 24–48 hr. Maximal cytostatic activity can be reinduced but only 48 hr or longer after the primary activators were removed. A transient period in which the Mφ-c are refractory to reactivation can be demonstrated to exist for 1–2 days after removal of the primary activators.
Remodeling of motor terminals during metamorphosis of the moth Manduca sexta: Expression patterns of two distinct isoforms of Manduca fasciclin II

During metamorphosis of the moth Manduca sexta, the neuromuscular system of the thoracic legs is reorganized dramatically. Larval leg muscles degenerate at the end of larval life, and new adult leg muscles develop during the ensuing pupal stage. Larval leg motoneurons persist, but undergo substantial remodeling of central and peripheral processes. As part of our on-going investigation of mechanisms underlying the remodeling of motor terminals, we have used antisera generated against Manduca-specific isoforms of the homophilic adhesion molecule fasciclin II (MFas II) to label motor terminals during metamorphosis. Antisera generated against the glycosyl-phosphatidylinositol (GPI) -linked isoform of MFas II (GPI-MFas II) labeled the motor nerves at all stages and seemed to be associated with glial cells ensheathing the peripheral nerves. In addition, the anti–GPI-MFas II antisera labeled regions associated with synaptic boutons at both larval and adult stages. In contrast, antisera generated against a transmembrane isoform of MFas II (TM-MFas II) only labeled specific neuronal processes at discrete intervals during remodeling. Identified leg motoneurons (such as the femoral depressor motoneuron) expressed detectable levels of TM-MFas II in their peripheral processes only during phases of motor-terminal retraction and initial stages of motor-terminal re-growth. Putative modulatory neurons (such as the unpaired median neurons), however, expressed TM-MFas II in their processes during larval stages as well as during remodeling. Use of the isoform-specific anti-MFas II antisera provided a novel method for visualizing remodeling of motor terminals during metamorphosis and helped distinguish different components of the motor nerves and neuromuscular junction. J. Comp. Neurol. 434:69–85, 2001. © 2001 Wiley-Liss, Inc.
Effects of dopamine depletion on the spontaneous activity of type I striatal neurons: Relation to local dopamine concentration and motor behavior

The relation between the electrophysiological activity of Type I striatal neurons, local dopamine (DA) concentration, and motor behavior in rats was investigated using intraventricular administration of the neurotoxin 6-hydroxydopamine (6-HDA) and extracellular single-unit recording. Results are compared with findings of past experiments in which the activity of Type II striatal neurons was examined after comparable 6-HDA-induced lesions. Several differences between the present observations and the earlier results were found. First, although large depletions (greater than 50%) of DA local to the site of the recording were required before the spontaneous firing rate of either cell type was increased, the levels necessary for this effect were found to be less for Type I cells than for Type II neurons. Second, although DA depletions of greater than 50% always were associated with increased Type I cell activity, depletions of greater than 95% resulted in spontaneous firing rates that were lower than those observed after depletions of approximately 90%. Thus, the relation between extent of dopaminergic depletion and Type I cell firing rate was biphasic, whereas that relation previously was found to be monophasic for Type II neurons. Finally, whereas increased Type I cell activity in the lateral striatum was associated with the aphagia, adipsia, and akinesia induced by large DA-depleting brain lesions, increased Type II cell activity in the medial striatum was found to be associated with these impairments. Because accumulating evidence suggests that the functioning of the lateral striatum is more critical for these behaviors, however, it is proposed that the substrate of the behavioral dysfunctions resulting from DA depletion is the Type I cell population in lateral striatum.
The reliable hub-and-spoke design problem: Models and algorithms

Abstract Hub-and-spoke structure is widely adopted in industry, especially in transportation and telecommunications applications. Although hub-and-spoke paradigm demonstrates significant advantages in improving network connectivity with less number of routes and saving operating cost, the failure of hubs and reactive disruption management could lead to substantial recovery cost to the operators. Thus, we propose a set of reliable hub-and-spoke network design models, where the selection of backup hubs and alternative routes are taken into consideration to proactively handle hub disruptions. To solve these nonlinear mixed integer formulations for reliable network design problems, Lagrangian relaxation and Branch-and-Bound methods are developed to efficiently obtain optimal solutions. Numerical experiments are conducted with respect to real data to demonstrate algorithm performance and to show that the resulting hub-and-spoke networks are more resilient to hub unavailability.
Have Your PIC

RNA polymerase II (Pol II), the enzyme that transcribes protein-coding genes, requires additional factors to accurately initiate transcription from promoter-directed start sites. These general transcription factors (GTFs) assemble with Pol II into a pre-initiation complex (PIC) that is a key intermediate in the transcription activation pathway ( 1 ). The main role of the GTFs is to accurately position and orient Pol II on the DNA template and to facilitate access of the catalytic site to the transcribed strand. Recent structural studies, including the cryoelectron microscopy (cryo-EM) reconstruction of the yeast PIC by Murakami et al. on page 709 of this issue ( 2 ), provide detailed views into the structural organization of this large complex. These studies will pave the way for a more complete understanding of how gene expression is regulated.
Radiation-induced plaque formation decreased by concomitant antioxidant diet in a hypercholesterolemic rabbit model

Purpose/Objective: Apoptotic cell death has been suggested to play an important role in the acute normal tissue injury induced by radiation. Accordingly, the ability to image radiation-induced apoptosis would aid in the detection and investigation of normal tissue injury resulting from radiotherapy as well as from environmental exposure. Near infrared optical fluorochromes can be utilized for imaging cellular events both in vivo and ex vivo. GSAO is an agent that is selectively bound in apoptotic cells. We now report on the use of 4-(N-(S-glutathionylacetyl)amino)pherylarsenoxide (GSAO) linked to the fluorochrome Cy5.5 for imaging apoptosis in the mouse spleen following total body irradiation (TBI).