cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of abnormal thyroglobulin in a transplantable rat thyroid tumor.

The soluble iodoproteins in a transplantable rat thyroid tumor (Wollman Line 1–8) were studied after in vivo labeling with 125I and were partially purified by affinity chromatography on anti-thyroglobulin-agarose. A major fraction (“Peak A”) was excluded from gels of large pore size, but had a low sedimentation rate (∼8S) and did not appear to contain aggregates. It had a high density (∼1.4) which was possibly due to a high content of carbohydrate, since treatment with a crude glycosidase mixture lowered the density to ∼1.3. A second fraction (“Peak B”) had a similar sedimentation coefficient (6–9S) but penetrated the same gels and had a lower density (∼1.3). Both proteins formed soluble complexes with antibodies against normal rat thyroglobulin, and had other properties somewhat similar to those of thyroglobulin. After hydrolysis, mono- and diiodotyrosine were the only iodoamino acids liberated. These iodoproteins appear to represent abnormal forms of thyroglobulin synthesized by the tumor. (Endocrinolog...
The holographic concept and macrosonics

Abstract The significance of the holographic concept is that it provides the means of dealing simultaneously with amplitude and phase information. The aim of this study is to show where in ultrasonics this concept can be used, in spite of the fact that both amplitude and phase information of a sound wave can be processed without the need of holographic techniques. This contrasts with the case in optics where phase information cannot be recorded by any other technique. The potential use of optical holography to improve the performance of ultrasonic transducers will be discussed, together with its application in the better understanding of events in high-power ultrasonics. A summary will be given of the present stage of sonic and ultrasonic holography in engineering and medicine.
Conservation Reserve Program: source or sink habitat for grassland birds in Missouri?

The Conservation Reserve Program (CRP) has been eredited with contributing substantially to the conservation of grassland birds. Although many species have nested in grasslands established under the CRP, little evidence of positive effect on populations has been reported. We measured reproductive rates and estimated fecundity of 7 grassland bird species in CRP fields in northern Missouri and compared those rates to estimates of fecundity needed to maintain stable populations (λ = 1). Under conservative assumptions of survival, CRP fields seemingly were source habitats (fecundity exceeded levels necessary for λ = 1) for grasshopper sparrows (Ammodramus savannarum) and field sparrows (Spizella pusilla) in at least 2 of 3 years (1993: P = 0.02, 1995: P < 0.001) and pooled over 3 years (Ps < 0.001). Although evidence was less compelling, CRP fields were likely source habitat for eastern meadowlarks (Sturnella magna) and American goldfinches (Carduelis tristis). For American goldfinches, fecundity was greater than that necessary for λ = 1 in 1995 (P < 0.001), and pooled over 3 years (P < 0.001). Our pooled estimate of fecundity was greater than necessary for λ = 1 for eastern meadowlarks (Ps < 0.001), but only under a liberal assumption of survival in 2 of 3 years (1993: P = 0.001; 1995: P = 0.088). Fecundity of common yellowthroats (Geothlypis trichas) varied substantially; therefore, source-sink status alternated among years, although the pooled estimate of fecundity was less than required for λ = 1 (P < 0.001). Dickcissel (Spiza americano) fecundity was consistently less than necessary for λ = 1 (conservative survival assumption: all Ps < 0.001; liberal survival assumption: 1994 P - 0.008. pooled P = 0.014). For red-winged blackbirds (Agelaius phoeniceus), CRP fields were consistently a sink habitat (all Ps < 0.001). Based on our evidence, the CRP likely has contributed to the conservation of grasshopper sparrows, field sparrows. and eastern meadowlarks. Although large numbers of dickcissels and red-winged black-birds nested in CRP fields, there is little evidence that the CRP has contributed to populations of those species.
Process of Symptom Production and Patterns of Symptom Maintenance

In the search for the process of symptom production, on the one hand, and for the patterns of symptom maintenance, on the other, lies the key difference between the two main orientations in the field of family therapy; the psychodynamic and the system-oriented approaches. They imply conceptual and operational hypotheses stemming from different logics, different sets of data, different lines of inquiry and, alas, different treatment strategies. Clearly distinctive traits of each of these two lines are discussed and exemplified, with special emphasis on the interactional, systemic view.
Methomyl in the Blood of a Pilot Who Crashed during Aerial Spraying

An aerial-spray pilot died when his aircraft crashed while he was spraying methomyl. We measured the pesticide in his blood by gas chromatography with flame photometric detection and confirmed the results by mass spectrometry with direct liquid injection through a liquid chromatography interface. The whole blood methomyl concentration was 570 ng/mL. Language: en
Pokeweed Antiviral Protein, a Ribosome Inactivating Protein: Activity, Inhibition and Prospects

Viruses employ an array of elaborate strategies to overcome plant defense mechanisms and must adapt to the requirements of the host translational systems. Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and is an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin (S/R) loop of large rRNA, arresting protein synthesis at the translocation step. PAP is thought to play an important role in the plant’s defense mechanism against foreign pathogens. This review focuses on the structure, function, and the relationship of PAP to other RIPs, discusses molecular aspects of PAP antiviral activity, the novel inhibition of this plant toxin by a virus counteraction—a peptide linked to the viral genome (VPg), and possible applications of RIP-conjugated immunotoxins in cancer therapeutics.
Formation and properties of RNA-DNA complexes*

The rate of formation of complexes between T2 RNA and T2 DNA has been measured at various salt concentrations (0·2 to 1·5 M -KCl) and temperatures (50 to 85°C). With increasing temperature, the rate passes through a maximum which is higher the higher the salt concentration. In 0·5 M -KCI the optimum temperature is 67°C. The rate of reaction is proportional to both the RNA and DNA concentration. The apparent bimolecular constant for five different preparations of T2 RNA was 2 ml./μg DNA/minute, or 10 l./mole nucleotides/second (in 0·5 M -KCI, 67°C, pH 7·3). This rate is several orders of magnitude slower than that for the reaction between polyadenylic acid and polyuridylic acid. Differences and similarities between the two reactions are discussed. Annealing in the absence of RNA causes T2 DNA to lose its RNA-binding ability. The second-order rate constant for this process is approximately the same as that for the RNA-DNA reaction. Under the conditions used for their formation, RNA-DNA complexes are slowly destroyed. The fraction of complex breaking down in unit time increases as the concentration of RNA-DNA complex increases. RNA-DNA complexes were broken down completely by RNase at low salt concentrations. The resistance to RNase increased with increasing salt concentration but was not complete under any condition tested. The complex was destroyed completely by DNase. The extent of complex formation was measured using an excess of either reactant. At least 77% of RNA formed after T2 infection of Escherichia coli is capable of becoming bound to T2 DNA. The binding capacity of T2 DNA is approximately 0·3 μg RNA/μg DNA.
Exploring the Limits of Methane Storage and Delivery in Nanoporous Materials

The physical limits for methane storage and delivery in nanoporous materials were investigated, with a focus on whether it is possible to reach a methane deliverable capacity of 315 cm3(STP)/cm3 in line with the adsorption target established by the ARPA-E agency. Our efforts focused on how both geometric and chemical properties, such as void fraction (Vf), volumetric surface area (Sv), and heat of adsorption (Qst), impact methane deliverable capacity, i.e., the amount of methane adsorbed at some storage pressure minus the amount adsorbed at the delivery pressure. With the aid of grand canonical Monte Carlo (GCMC) simulations, we studied methane adsorption and delivery properties in a population of 122 835 hypothetical pcu metal–organic frameworks (MOFs) and 39 idealized carbon-based porous materials. From the simulation results, we developed an analytical equation that helped us delimit the necessary material properties to reach specific methane deliverable capacity targets. The maximum deliverable capaci...
GaN nanostructures and HFET structures selectively grown on silicon substrates by ammonia-MBE

Silicon substrate can be used as a highly effective pseudomask to perform selective growth of GaN by ammonia molecular beam epitaxy (MBE). This can be exploited to fabricate novel photonic and electronic device structures on Si substrates. Growth of GaN micro-pyramids as templates for fabricating InGaN quantum dots, and growth of AlGaN/GaN HFET mesa patterns using the selective growth approach is reported. The facet growth characteristics of the selectively grown GaN micro-pyramids are investigated. μ-photoluminescence (μ-PL) measurements resolving emissions from InGaN quantum dots and/or wells on a single GaN pyramid have been performed, but have found no evidence of formation of InGaN single quantum dot at the apex of the GaN pyramid. Possible improved growth approaches for achieving such single quantum dot structures are discussed. Success in selective growth of the HFET mesa pattern and especially the insulating carbon-doped GaN buffer layer is achieved, demonstrating a promising approach for potential integration of nitride devices with silicon circuits.
Cytoprotection by inhibition of chloride channels: the mechanism of action of glycine and strychnine.

Abstract Previous studies have demonstrated that strychnine mimics the cytoprotective effects of glycine (1) and that strychnine binds specifically to renal proximal tubules (RPT) at cytoprotective concentrations (2). The goal of this study was to determine a mechanism by which strychnine and glycine are cytoprotective. Antimycin A (0.1 μM) caused chloride influx subsequent to mitochondrial inhibition and prior to the release of lactate dehydrogenase (LDH) activity (a marker of cell death/lysis). The addition of strychnine or glycine prevented the chloride influx and LDH release. The chloride channel inhibitors ethacrynic acid, furosemide, anthracene-9-carboxylic acid, DIDS, and SITS decreased LDH release in RPT exposed to antimycin A with a rank order of potency of DIDS > ethacrynic acid=furosemide=anthracene-9-carboxylic acid > SITS. These data, in conjuction with the preceeding paper, indicate a critical role for chloride influx in cell death/lysis; support the existence of a novel strychnine binding site on the plasma membrane of RPT that is coupled to a chloride channel; and suggest that glycine and strychnine are cytoprotective through their inhibition of chloride influx.
The Fate of Policy Analysis in Congressional Decision Making: Three Types of Use in Committees

TW A TITHIN the past two decades, Congress has dramatically enhanced its analytic capability, increasing the number and responsibilities of its professional staff (Malbin 1979; Salisbury and Shepsle 1981) and the quantity and quality of its analytic information (Commission on the Operation of the Senate 1976; Frantzich 1982). Two new congressional support agencies have been created, the Office of Technology Assessment and Congressional Budget Office, and the policy analysis components of the other two, the Congressional Research Service and General Accounting Office, have been significantly upgraded. The fate of policy analysis in congressional decision making, however, remains unclear. Research on the use of analytic information has focused almost exclusively on the executive branch, perhaps in response to suggestions that the potential for using policy analysis in Congress appeared to be quite limited (Davidson 1976; Jones 1976; Dreyfus 1977). In addition, research on congressional decision making has yet to produce models which explicitly connect floor voting choices, which are not likely to be directly influenced by policy analysis, with the activities which precede and structure those choices, activities in which the influence of analytic information is likely to be much stronger. This article is an attempt to provide some theoretical context and empirical underpinning to discussions of both the use of policy analysis in Congress and the implications of that use for congressional decision making. Such an endeavor contributes in two more general ways to a greater understanding of the role of analysis in public decision making. First, it extends the scope of research, which has been largely restricted to administrative organizations. Investigating the use of policy analysis in a legislative environment forces explicit attention to the political factors which affect use, something often ignored. Second, the legislative setting presents, in stark terms, the basic "difficulty of combining expert advice with democratic political institutions," which MacRae contends is "a major problem of contemporary democratic societies" (1976: 169). Congress, the institution once envisioned to be tied most closely to the common sense of the common man, is now being confronted with increasingly complex problems that appear to require considerable specialized knowledge. An
Measurement of helium leak rates with temperature and pressure in RHIC

The changes in helium leak rates with pressure and temperature from helium-cooled magnet vessels into insulating vacuum were measured. The leak rates increased by three orders of magnitude when the vessels were cooled from ambient temperature to 4.5 K. The changes in leak rates were found to be smaller than those of a viscous flow through a capillary tube.
Rsf1p is required for an efficient metabolic shift from fermentative to glycerol‐based respiratory growth in S. cerevisiae

Previous studies from this laboratory indicated that the product of the RSF1 gene of S. cerevisiae is present in both nucleus and mitochondria, and they suggested that Rsf1p acts as a transcriptional modulator. To investigate this latter question, we performed transcriptome profiling of an rsf1 mutant strain and its wild-type parent during a shift from glucose-based fermentative to glycerol-based respiratory growth to identify genes whose expression is regulated by Rsf1p. Loss of Rsf1p engendered a decrease in transcript levels from many genes encoding components of the electron transport chain and various other mitochondrially-localized products. The earlier studies further showed that rsf1 cells exhibit a growth defect on medium containing glycerol, but not ethanol, as sole carbon source. Importantly, transcriptome profiling of the rsf1 mutant during shift from glucose- to glycerol-based medium revealed that the product of this gene plays a major role in both orchestration of the transition to, and maintenance of, efficient growth on glycerol as sole carbon source. An increase in transcript levels from genes encoding products that function in the stress response, and an imbalance between expression of genes encoding glycerol anabolic and catabolic enzymes, was observed in the rsf1 mutant during steady-state growth on glycerol- but not ethanol-based medium; this suggests the presence of partially separate transcriptional regulatory systems for transition to respiratory growth on each of these two carbon sources. Genes whose expression is affected by loss of Rsf1p, which lacks a known DNA-binding motif, lack a common DNA sequence motif in their upstream regions. These and other data presented here strongly suggest that the transcriptional effects exerted by Rsf1p are mediated via interaction with other transcription factors. Copyright © 2009 John Wiley & Sons, Ltd.
THE USE OF COLLATERAL TO ENFORCE DEBT: PROFIT MAXIMIZATION

Collateral lowers the probability of default. This paper modifies the work of Benjamin (1978) by characterizing the competitive lender as a price-taking profit maximizer rather than a profit eliminator. Most of Benjamin's results disappear when profit maximization is assumed; the results are corrected and extended. It is also suggested that the value of the collateral required for a standard loan is a variable that the loan market will adjust until long-run expected profits from secured loans is driven to zero.
Transient Wave Propagation in a Materially Nonlinear Beam

In this paper, the transient wave propagation in a materially nonlinear beam is studied. Based on previous research, the geometric nonlinearity can be neglected in an intermediate strain regime. An equation of motion for a cubic material nonlinearity is derived. The alternating frequency-time finite element method (AFT-FEM) is applied to the beam model. Numerical simulations are conducted. Significant nonlinear behavior is observed in the response. Depending on the local nonlinear property of the material in the intermediate strain regime, the amplitude of the wave response can be influenced. The nonlinear properties can also influence the dispersive characteristics of the intrinsically dispersive beam model.Copyright © 2013 by ASME
Genetic influence on tonic immobility in chickens

Production Red chickens were selectively bred on the basis of having shown prolonged or brief immobility reactions at 21 days of age. After only one generation, there was sufficient separation between offspring to conclude that tonic immobility has an unusually large heritability component. Results were discussed in terms of their implications for an evolutionary model of animal hypnosis.
The effect of metal silicide formation on silicon nanowire-based lithium-ion battery anode capacity

Abstract There is great interest in one-dimensional (1D) nanostructures that allow lateral relaxation and can be used to reduce pulverization of a silicon-based anode material. However, the growth of high density arrays of silicon nanowires (SiNWs) on metal current collectors using a chemical vapor deposition (CVD) processing is challenging due to competing metal silicide formation during the Si nanowire growth process. An issue with the metal silicide formation is that Si is consumed and this reduces the overall specific capacity as well as the rate capability of a silicon nanowire-based anode material. Here, we demonstrate high density, electrically contacted Si nanowire growth on stainless steel substrates (metal current collectors) with minimal unwanted substrate-silicide formation for high Li ion battery performance. These high-purity silicon nanowire-based anodes show average high specific capacities of 3670 mA h g −1 at 0.2 C and 3448 mA h g −1 at 0.5 C over 40 cycles. Moreover, the high-purity silicon nanowires are demonstrated to reach extremely high capacities at high cycle rates (1912 mA h g −1 and 997 mA h g −1 at 10 C and 20 C, respectively).
The role of intertidal egg deposition on survival of the puffer, Takifugu niphobles (Jordan et Snyder), embryos

Abstract The puffer, Takifugu niphobles (Jordan et Snyder), is an intertidal spawner; the spawning linkage with the tidal cycle makes it possible for the puffer to spawn at the upper intertidal zone. To test whether the intertidal spawning is an adaptation to maximize egg survival, the location of egg deposition and the most suitable location for egg survival were determined. An egg-trap experiment indicated that eggs were scattered around the spawning zone and never moved downwards into the lower intertidal zone. The eggs were stranded under pebbles of the upper intertidal zone, and developed there. Some of the stranded eggs died apparently because of high temperatures and desiccation during periods of exposure. An egg-transplantation experiment indicated that throughout the spawning season, mortality of eggs by physical stress was lower in the lower intertidal zone (where eggs were never found naturally) than in the upper zone. Also, the loss rate due to predation or wave action did not differ among the tidal zones. These facts suggest that the upper intertidal spawning linked with the tidal cycle does not maximize egg survival, and that the puffer should spawn during lower tides in the tidal cycles.
Scanning SQUID microscopy of vortex configurations in superconductor arrays

Abstract We have imaged the configuration of magnetic vortices in 2D networks of superconducting Nb wires using a Scanning SQUID Microscope (SSM). The SSM scans a dc SQUID detector over the array to map out the magnetic field with a spatial resolution of 10μm and a flux sensitivity of 10 −4 Φ 0 . We have studied the arrangement of vortices in large square arrays as a function of the applied magnetic field.
Recent Developments in Cloud Computing, Data Storage and Handling

As data center managers consider deployment of a Cloud Computing environment the most important issues they consider include critical application data availability, storage agility and data protection strategies. Early adopters of Cloud Computing have already deployed Virtualization as a key technology in their Infrastructure as a Service (IaaS) and Platform as a Service (PaaS) offerings. Cloud computing extends the benefits of virtualization by increasing the efficiency of server and storage utilization, reducing costs, improving operational efficiency and optimizing datacenter rack and floor space. It builds on first-generation system and storage virtualization with features such as application portability and storage agility to enable higher efficiencies and greater efficiencies across the enterprise. With recent innovation in storage, key features such as thin-provisioning, compression and de-duplication work in concert with virtualized infrastructure on the Storage Appliance to eliminate duplicate data blocks, compress data and allocate the amount of storage being consumed by users. Data services such as snapshots and clones provide instant and optionally, unattended backups that can be used in the short term for recovery of critical data. Disaster recovery is all the more important within the cloud computing environment and built in replication services enable a robust solution in case of a catastrophic event or simply for purposes of backup and recovery.Copyright © 2013 by ASME
Swept under the rug: the problem of unacknowledged ambiguity in lithic residue identification

Abstract Microscopic analysis of organic residues on stone tools is used to interpret prehistoric stone tool functions. The morphology of some residues can be difficult to interpret, yet this ambiguity is rarely acknowledged in the literature. Our research seeks to understand the nature of this ambiguity by objectively identifying ambiguous residues in our reference collection. We trained four archaeologists in residue analysis using one part of our reference collection, then tested their ability to identify sixty-eight residues in another part of the same collection. Forty-eight of the residues in the test (70%) were correctly identified by three or all four subjects. We considered the remaining twenty residues, which were correctly identified by two or fewer of the subjects, to be ambiguous. These are most often in the hide-scraping, bone-scraping, and hardwood-scraping (macerated) categories, and tend to have an atypical morphology which falls in the range of variability of another residue category. Some of these residues also have optical properties which make them more difficult to image than others. We explore the potential for scanning electron microscopy (SEM) to improve residue identification in a second test. This test shows a modest improvement in identification success rates of ambiguous residues when SEM images are included. We conclude that while images from different types of microscopes can improve reliability of identification, some residues will always be ambiguous. Rather than being ignored, these ambiguities should be brought to light, closely examined, and published as such.
Effect of diffusion boundary layers on the initial uptake of O2 by red cells. Theory versus experiment

We have applied theories of mass transfer, in laminar and turbulent flow, to red cells in the stopped-flow apparatus in order to estimate the effect of extracellular diffusion boundary layers on the initial rate of O2 uptake. We compared the theoretical predictions with the results of our previous stopped-flow experiments with suspensions of red cells to which bovine serum albumin (BSA) had been added to decrease O2 solubility and diffusivity (Huxley and Kutchai, 1981). Models of red cells in laminar flow (Friedlander, 1957, 1961; Harriott, 1962) predict a significant retardation of the rate of O2 entry into red cells by diffusion boundary layers. Mixing in the stopped-flow apparatus occurs by convective and turbulent mechanisms in addition to simple molecular diffusion. The more complex theory of mass transfer to particles in turbulent flow (Levich, 1962) shows, because the red cells are highly entrained in the flow, that mixing is not complete on the time scale of initial O2 uptake. The O2 permeability of the diffusion boundary layer, predicted by both laminar and turbulent flow theories, approximates the experimentally obtained value. The theories of mass transfer to particles in laminar flow predict the dependence of the rate of O2 uptake on red cell size observed by other investigators. This suggests that these experimental results may be primarily due to the effect of diffusion boundary layers. Our studies are consistent with the interpretation that red cells in rapid mixing devices may be mixed incompletely with the suspending fluid; thus O2 transfer is limited by molecular diffusion in the immediate vicinity of the erythrocyte. We conclude that the rates of respiratory gas exchange by red cells in flowing systems may be partly limited by diffusion boundary layers.
Constraint Dynamics of Particle World Lines

The Dirac generator fomulations for relativistic Hamiltonian dynamics is extended by explicitly separating the question of dynamical evolution in an inertial frame from that of changes of frame. We obtain a new elevengenerator formalism: ten to realize the Poincare Lie algebra, and one to provide equations of motion. For point-particle systems, a new form of the world-line conditions is developed. It is demonstrated that with these extensions one can consistently describe classical point particles with interaction in a relativistically invariant way while maintaining invariant world lines. This paper uses the approach based on independent particle variables to set up such theories.
Recurrent Restricted Phenotypic Selection for Improving Stand Establishment of Bahiagrass

Bahiagrass (Paspalum notatum Flugge) is an important perennial forage grass for the south- eastern United States, being well adapted to conditions such as sandy or poorly drained soils, drought, and heavy continuous grazing. Current bahiagrass cultivars germinate over an extended period of time and the slow emergence produces incomplete stands, allowing weeds to compete and delaying grazing or fi rst cutting for hay. A recurrent restricted phenotypic selection (RRPS) program began in 1996 and continued for four cycles for improving the emergence and establishment rates within Tifton 9 bahiagrass ('Pensacola' type). The resulting cycle-4 (C4) rapid-emergence 'TifQuik' was then increased and tested for seedling emergence, vigor, and establishment. TifQuik had a fourfold improve- ment of emergence compared to Tifton 9 after 1 wk in greenhouse trials. Emergence rates after 1 and 2 wk were signifi cantly greater for TifQuik compared to Tifton 9 in replicated fi eld trials. Plant heights after 3 wk from planting were 0.12 m for TifQuik versus 0.08 m for Tifton 9. The fi rst- harvest dry-matter yield of TifQuik was 3128 kg ha -1 compared with 1539 kg ha -1 for Tifton 9 and the total establishment year dry-matter yields were 9230 kg ha -1 and 7466 kg ha -1 for TifQuik and Tifton 9, respectively. TifQuik had greater fi rst-clipping yields than Tifton 9 at Ona, FL, in 2005. The accelerated emergence and estab- lishment of TifQuik will be useful in sod-based rotation systems with cotton (Gossypium hirsu- tum L.) and peanut (Arachis hypogaea L.).
STRATEGY FOR INCREASED EFFICIENCY OF TRANSFECTION IN HUMAN CELL LINES USING RADIO FREQUENCY ELECTROPORATION

Traditional electroporation devices use direct current electric fields to stimulate the uptake of oligonucleotides, plasmids, short peptides, and proteins into a variety of cell types. A variation of this widely used technique is now available which relies on radio frequency (RF) electrical pulses. This oscillating type of electrical field reportedly elicits greater uptake of plasmid DNA across the plasma membrane. We evaluated a protocol for RF electroporation of the a human embryonic kidney cell line and a Burkitt's lymphoma (BL) cell line for effeciency of transfection by RF electroporation. The plasmid EGFP, which codes for the widely used fusion protein, enhanced green fluorescent protein (EGFP), was used as a reporter of plasmid uptake after transfections. Transfection efficiency consistently increased approximately 30% from that typically obtained with conventional DC type electroporation and was accompanied by greater survivability of cells. Additionally, in some instances, percent transfection ef...
Synthesis of folate-conjugated amphiphiles for tumor-targeted drug delivery.

Folic acid was derivatized specifically at its γ-carboxyl group to retain its ligand-binding activity to the folate receptor α (FRα) present on HeLa cells. Amphiphilic molecules labeled with folic acid were prepared by conjugation of long-chain primary amines directly or via diamine linkers to the γ-carboxyl group of folic acid. Folic acid amphiphiles labeled with fluorescent 7-amino-4-carbamoylmethylcoumarin (ACC) were also prepared to visualize the uptake of amphiphiles in folate receptor positive cells. The structures of the new compounds were verified by proton NMR and MALDI-TOF mass spectrometry. The amphiphiles form micelles in water. Critical micelle concentrations (CMCs) were determined by the pyrene fluorescence method for folic acid amphiphiles and the rise in capillary height method for the fluorescently labeled amphiphile. The CMCs of the amphiphiles were studied in buffer solution at pH 8 and ranged from 2 to 64 μM. The formation of micelle increased the solubility of paclitaxel, a model lipo...
Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties

Optical reflectance probes are often used as tools to obtain optical spectra from superficial tissues and subsequently determine optical and physiological properties associated with early stage cancer. These probes, when placed directly on the tissue, are known to cause significant pressure-dependent changes in local optical properties. To address this, we fit the probe with an optical device that images the illumination and collection fibers onto the tissue surface, eliminating the influence of contact probe pressure on the sampling area. The noncontact probe addition addresses new optical conditions that may affect its performance such as tissue surface contour, and specular reflections by implementing an autofocusing mechanism and cross polarization. Extracted optical properties of tissue simulating phantoms yield errors of 3.46% in reduced scattering and 8.62% in absorbance. Autofocusing has extended the depth of field from 4 mm to throughout the 12 mm range of autofocus travel, while cross polarization has removed the incidence angle dependent specular reflection component from the collected signal.
Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

Nitroxides can undergo one- or two-electron reduction reactions to hydroxylamines or oxammonium cations, respectively, which themselves are interconvertible, thereby providing redox metabolic actions. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) is the most extensively studied nitroxide. It is a cell membrane-permeable amphilite that dismutates superoxide catalytically, facilitates hydrogen peroxide metabolism by catalase-like actions, and limits formation of toxic hydroxyl radicals produced by Fenton reactions. It is broadly effective in detoxifying these reactive oxygen species in cell and animal studies. When administered intravenously to hypertensive rodent models, tempol caused rapid and reversible dose-dependent reductions in blood pressure in 22 of 26 studies. This was accompanied by vasodilation, increased nitric oxide activity, reduced sympathetic nervous system activity at central and peripheral sites, and enhanced potassium channel conductance in blood vessels and neurons. When administered orally or by infusion over days or weeks to hypertensive rodent models, it reduced blood pressure in 59 of 68 studies. This was accompanied by correction of salt sensitivity and endothelial dysfunction and reduced agonist-evoked oxidative stress and contractility of blood vessels, reduced renal vascular resistance, and increased renal tissue oxygen tension. Thus, tempol is broadly effective in reducing blood pressure, whether given by acute intravenous injection or by prolonged administration, in a wide range of rodent models of hypertension.
Current advances in treatment of gastroparesis

Introduction: Gastroparesis is a syndrome defined by delayed gastric emptying in the absence of mechanical obstruction. Gastroparesis has significant symptomatology and negative impacts on the patient’s quality of life.Areas covered: This article reviews current treatment options for gastroparesis, recent advances in treatment and future directions that treatment may head. Current options are broadly divided into prokinetics and symptom modulators. Within each group, current modalities as well as recent advances are discussed according to agent mechanism of action. Lastly, findings regarding the cellular pathophysiology involved in gastroparesis will be briefly reviewed along with their implications for future treatments.Expert opinion: The numerous motor functions and neural inputs that control gastric motility are complex and not fully understood. Our lack of understanding of its pathophysiology has led to treatment options which are empirical, palliative and often ineffective. Newly intensified interes...
Astrocyte- and hepatocyte-specific expression of genes from the distal serpin subcluster at 14q32.1 associates with tissue-specific chromatin structures

The distal serpin subcluster contains genes encoding α1-antichymotrypsin (ACT), protein C inhibitor (PCI), kallistatin (KAL), and the KAL-like protein that are expressed in hepatocytes but only the act gene is expressed in astrocytes. We show here that the tissue-specific expression of these genes associates with astrocyte- and hepatocyte-specific chromatin structures. In hepatocytes, we identified twelve DNase I-hypersenitive sites (DHS) that were distributed throughout the entire subcluster, with the promoters of expressed genes accessible to restriction enzyme digestion. In astrocytes, only six DHSs were located exclusively in the 5′ flanking region of the act gene, with its promoter also accessible to restriction enzyme digestion. The acetylation of histone H3 and H4 has been found throughout the subcluster in both cell types but this acetylation did not correlate with the expression pattern of these serpin genes. Analysis of histone modifications at the promoters of the act and pci genes revealed that methylation of histone H3 on lysine 4 correlates with their expression pattern in both cells types. In addition, inhibition of methyltransferase activity resulted in suppression of ACT and PCI mRNA expression. We propose that lysine 4 methylation of histone H3 correlates with the tissue-specific expression pattern of these serpin genes.
Comparison of Selective Broth Medium Plus Neomycin-Nalidixic Acid Agar and Selective Broth Medium Plus Columbia Colistin-Nalidixic Acid Agar for Detection of Group B Streptococcal Colonization in Women

The combination of neomycin-nalidixic acid (NNA) agar and a selective broth medium (SBM) has recently been shown to improve the sensitivity of screening cultures for group B streptococcal (GBS) carriage in women. Because of the relatively high cost of NNA agar, a study was initiated to determine whether Columbia colistin-nalidixic acid (CNA) agar would be an equally sensitive, more economical alternative. A total of 580 cervical-vaginal and/or rectal specimens submitted for detection of GBS were included in the study. Each was plated onto NNA and CNA agar and then inoculated into SBM. GBS were recovered from 95 of 580 (16.4%) specimens, including 61 isolates from CNA, 74 from NNA, 73 from the CNA-SMB combination, and 86 from the NNA-SMB tandem. Of those, 22 isolates were recovered on NNA but not CNA, 9 were cultured on CNA but not NNA, 52 were isolated on both media, and 12 were recovered from subcultures of SBM only. The overall sensitivity of CNA alone (64.2%) was statistically significantly less than that of NNA agar (77.9%), as was the sensitivity of combination of CNA plus SBM (76.8%) compared to that of NNA plus SBM (90.5%). Based on these findings, CNA should not be considered an acceptable alternative to NNA for the detection of GBS colonization in women despite potential cost savings.
Localization and activation of glucagon-like peptide-2 receptors on vagal afferents in the rat.

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal growth through poorly understood paracrine and/or neural pathways. The relationship between GLP-2 action and a vagal pathway is unclear. Our aims were to determine whether 1) the GLP-2 receptor (GLP-2R) is expressed on vagal afferents by localizing it to the nodose ganglia; 2) exogenous GLP-2 stimulates the vagal afferent pathway by determining immunoreactivity for c-fos protein in the nucleus of the solitary tract (NTS); and 3) functional ablation of vagal afferents attenuates GLP-2-mediated intestinal growth in rats maintained with total parenteral nutrition (TPN). A polyclonal antibody against the N terminus of the rat GLP-2R was raised and characterized. The GLP-2R was localized to vagal afferents in the nodose ganglia and confirmed in enteroendocrine cells, enteric neurons, and nerve fibers in the myenteric plexus using immunohistochemistry. Activation of the vagal afferent pathway, as indic...
A matched filter detection system for complicated Doppler shifted signals

A matched filter system is described which was designed to detect complicated signals subject to a wide range of possible Doppler shifts. A 100 tap band-pass delay line was used in conjunction with a resistor weighting matrix to synthesize signals and filter characteristics. The system could handle a signal with a duration-bandwidth product of 100 over a range of Doppler frequency shifts 17 times the reciprocal of the signal duration. A theoretical discussion of the Doppler effect is given, making use of conjugate functions or Hilbert Transforms. Various engineering compromises which simplify the construction of matched filters are suggested. The performance of the resulting signal detection system was within 5 db of that of an ideal theoretical model.
Temporary esophageal stenting allows healing of esophageal perforations following atrial fibrillation ablation procedures.

Esophogeal Perforation, Stenting, and AF Ablation. Background: Left atrial catheter ablation (LACA) has emerged as a successful method to eliminate atrial fibrillation (AF). Recent reports have described atrio-esophageal fistulas, often resulting in death, from this procedure. Temporary esophageal stenting is an established therapy for malignant esophageal disease. We describe the first case of successful temporary esophageal stenting for an esophageal perforation following LACA. Case: A 48-year-old man with symptomatic drug refractory lone AF underwent an uneventful LACA. Fifty-nine ablations with an 8-mm tip ablation catheter (30 seconds, 70 Watts, 55°C), as guided by 3-D NavX™ mapping, were performed in the left atrium to isolate the pulmonary veins as well as a left atrial flutter and roof ablation line. In addition, complex atrial electrograms in AF and sites of vagal innervation were ablated. Two weeks later, he presented with sub-sternal chest pain, fever, and dysphagia. A chest CT showed a 3-mm esophageal perforation at the level of the left atrium with mediastinal soiling and no pericardial effusion. An urgent upper endoscopy with placement of a PolyFlex removable esophageal stent to seal off the esophago-mediastinal fistula was performed. After 3 weeks of i.v. antibiotics, naso-jejunal tube feedings, and esophageal stenting, the perforation resolved and the stent was removed. Over 18 months of follow-up, there have been no other complications, and he has returned to a physically active life and remains free from AF on previously ineffective anti-arrhythmic drugs. Conclusion: Early diagnosis of esophageal perforations following LACA may allow temporary esophageal stenting with successful esophageal healing. Prompt chest CT scans with oral and i.v. contrast should be considered in any patient with sub-sternal chest pain or dysphagia following LACA.
On-line automated performance diagnosis on thousands of processes

Performance analysis tools are critical for the effective use of large parallel computing resources, but existing tools have failed to address three problems that limit their scalability: (1) management and processing of the volume of performance data generated when monitoring a large number of application processes, (2) communication between a large number of tool components, and (3) presentation of performance data and analysis results for applications with a large number of processes. In this paper, we present a novel approach for finding performance problems in applications with a large number of processes that leverages our multicast and data aggregation infrastructure to address these three performance tool scalability barriers.First, we show how to design a scalable, distributed performance diagnosis facility. We demonstrate this design with an on-line, automated strategy for finding performance bottlenecks. Our strategy uses distributed, independent bottleneck search agents located in the tool agent processes that monitor running application processes. Second, we present a technique for constructing compact displays of the results of our bottleneck detection strategy. This technique, called the Sub-Graph Folding Algorithm, presents bottleneck search results using dynamic graphs that record the refinement of a bottleneck search. The complexity of the results graph is controlled by combining sub-graphs showing similar local application behavior into a composite sub-graph.Using an approach that combines these two synergistic parts, we performed bottleneck searches on programs with up to 1024 processes with no sign of tool resource saturation. With 1024 application processes, our visualization technique reduced a search results graph containing over 30,000 nodes to a single composite 44-node graph sub-graph showing the same qualitative performance information as the original graph.
Ror2 Enhances Polarity and Directional Migration of Primordial Germ Cells

The trafficking of primordial germ cells (PGCs) across multiple embryonic structures to the nascent gonads ensures the transmission of genetic information to the next generation through the gametes, yet our understanding of the mechanisms underlying PGC migration remains incomplete. Here we identify a role for the receptor tyrosine kinase-like protein Ror2 in PGC development. In a Ror2 mouse mutant we isolated in a genetic screen, PGC migration and survival are dysregulated, resulting in a diminished number of PGCs in the embryonic gonad. A similar phenotype in Wnt5a mutants suggests that Wnt5a acts as a ligand to Ror2 in PGCs, although we do not find evidence that WNT5A functions as a PGC chemoattractant. We show that cultured PGCs undergo polarization, elongation, and reorientation in response to the chemotactic factor SCF (secreted KitL), whereas Ror2 PGCs are deficient in these SCF-induced responses. In the embryo, migratory PGCs exhibit a similar elongated geometry, whereas their counterparts in Ror2 mutants are round. The protein distribution of ROR2 within PGCs is asymmetric, both in vitro and in vivo; however, this asymmetry is lost in Ror2 mutants. Together these results indicate that Ror2 acts autonomously to permit the polarized response of PGCs to KitL. We propose a model by which Wnt5a potentiates PGC chemotaxis toward secreted KitL by redistribution of Ror2 within the cell.
Differential role of beta-arrestin ubiquitination in agonist-promoted down-regulation of M 1 vs M 2 muscarinic acetylcholine receptors

Sustained agonist-promoted ubiquitination of β-arrestin has been correlated with increased stability of the GPCR – β-arrestin complex. Moreover, abrogation of β-arrestin ubiquitination has been reported to inhibit receptor internalization with minimal effects on receptor degradation. Herein we report that agonist activation of M1 mAChRs produces a sustained β-arrestin ubiquitination but no stable co-localization with β-arrestin. In contrast, sustained ubiquitination of β-arrestin by activation of M2 mAChRs does result in stable co-localization between the M2 mAChR and β-arrestin. Internalization of receptors was unaffected by proteasome inhibitors, but down-regulation was significantly reduced, suggesting a role for the ubiquitination machinery in promoting down-regulation of the receptors. Given the ubiquitination status of β-arrestin following agonist treatment, we sought to determine the effects of β-arrestin ubiquitination on M1 and M2 mAChR down-regulation. A constitutively ubiquitinated β-arrestin 2 chimera in which ubiquitin is fused to the C-terminus of β-arrestin 2 (YFP-β-arrestin 2-Ub) significantly increased agonist-promoted down-regulation of both M1 and M2 mAChRs, with the effect substantially higher on the M2 mAChR. Based on this observation, we were interested in examining the effects of disruption of potential ubiquitination sites in the β-arrestin sequence on receptor down-regulation. Agonist-promoted internalization of the M2 mAChR was not affected by expression of β-arrestin lysine mutants lacking putative ubiquitination sites, β-arrestin 2K18R, K107R, K108R, K207R, K296R, while down-regulation and stable co-localiztion of the receptor with this β-arrestin lysine mutant were significantly reduced. Interestingly, expression of β-arrestin 2K18R, K107R, K108R, K207R, K296R increased the agonist-promoted down-regulation of the M1 mAChR but did not result in a stable co-localiztion of the receptor with this β-arrestin lysine mutant. These findings indicate that ubiquitination of β-arrestin has a distinct role in the differential trafficking and degradation of M1 and M2 mAChRs.