cssi/SciSciGPT-SciSciNet huggingface dataset:
Relationship between opioids and activation of phospholipase C and protein kinase C in brain injury induced pial artery vasoconstriction

Abstract Previously, it has been observed that newborn pig pial artery constriction after fluid percussion brain injury was associated with elevated CSF dynorphin and β endorphin concentration. Additionally, brain injury reversed dynorphin-induced pial artery vasodilation to vasoconstriction. The present study was designed to characterize the relationship between opioids and activation of phospholipase C (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction. Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9–2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Brain injury decreased pial arteriolar diameter within 10 min of injury and continued to fall progressively for 3 h (130 ± 5, 108 ± 4 and 102 ±5 μm for 0, 10 and 180 min postinjury). In contrast, the PLC inhibitor, neomycin (10−4 M), blunted brain injury-induced pial vasoconstriction (133 ± 4, 129 ± 4 and 135 ± 5 μm for 0, 10 and 180 min postinjury, respectively). Similarly, staurosporine (10−7 M), a PKC inhibitor, also blunted brain injury-induced vasoconstriction. β endorphin (10−8, 10−6 M)-induced pial artery vasoconstriction was blunted by neomycin (12 ± 1, 19 ± 1 vs. 2 ± 1, 4 ± 2% constriction before and after neomycin, respectively. Staurosporine similarly blunted β endorphin pial constriction (10 ± 1, 15 ± 1 vs. 1 ± 1, 1 ± 1 % constriction before and after staurosporine, respectively). The constrictor potential for dynorphin was also inhibited by neomycin and staurosporine. These data indicate that brain injury-induced pial artery constriction is mediated, at least in part, by activation of PLC and PKC. Further, since CSF dynorphin and β endorphin concentrations are increased after brain injury, these data suggest that these two opioids contribute to activation of PLC and PKC observed after brain injury.
Effect of thermal noise on current-voltage characteristics of Josephson junctions

Measurements are reported of the current-voltage ($I\ensuremath{-}V$) characteristics of externally shunted oxide-barrier tunnel junctions at temperatures $T$ and critical currents ${I}_{c}$ such that the Josephson coupling energy $(\frac{\ensuremath{\hbar}}{2e}){I}_{c}$ is comparable to the thermal energy $kT$. The measurements are in complete quantitative agreement with the theory of Ambegaokar and Halperin in the limit that the dimensionless parameter ${\ensuremath{\beta}}_{c}=(\frac{2e}{\ensuremath{\hbar}})(\frac{{I}_{c}C}{{\ensuremath{\sigma}}^{2}})\ensuremath{\ll}1$, where $C$ is the capacitance and $\ensuremath{\sigma}$ the total conductance of the shunted junction. Measurements for larger values of ${\ensuremath{\beta}}_{c}$ are in qualitative agreement with the theory of Kurkij\"arvi and Ambegaokar. In addition, the Ambegaokar-Halperin theory is generalized to include the $cos\ensuremath{\phi}$ pair-quasiparticle interference term. It is concluded that a measurement of the $cos\ensuremath{\phi}$ term using only the $I\ensuremath{-}V$ characteristic will be difficult.
Role of noninvasive imaging using computed tomography for detection and quantification of coronary atherosclerosis.

Clinical cardiac computed tomography (CT) began with electron-beam CT in the early 1980s and continues now with multidetector CT in the 21st Century. The major applications of noncontrast cardiac CT are currently for the quantification of coronary artery calcium – a reliable and repeatable means to estimate atherosclerotic plaque burden. The major applications of contrast-enhanced CT (CT angiography) is for a more detailed estimation of total plaque burden by qualitatively defining noncalcified and complex plaque as well as ruling out obstructive coronary artery disease. Both of these applications are discussed and comments are made from the author regarding clinical applications based upon reviewing the published literature and through personal experience.
Synthesis of a C-linked hyaluronic acid disaccharide mimetic

Abstract The synthesis of a C-disaccharide that is designed as a mimetic for the repeating unit disaccharide of hyaluronic acid is described. The target compound was obtained via the SmI2-promoted coupling reaction of the sulfone, 2-acetamido-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1,2-dideoxy-1-pyridinylsulfonyl-β- d -glucopyranose (6), and the aldehyde, p-methoxyphenyl 2,3-di-O-benzyl-4-deoxy-4-C-formyl-6-O-p-methoxybenzyl-β- d -glucopyranoside (14).
Endogenous Glucocorticoids Induced by a Chemical Stressor (Ethanol) Cause Apoptosis in the Spleen in B6C3F1 Female Mice

Stress-induced increases in glucocorticoid levels can cause-apoptosis in immature thymocytes, but it is not known if glucocorticoids at these levels can also cause apoptosis in peripheral lymphocytes. In the present study, mice were exposed to ethanol (EtOH) in a model designed to represent binge drinking. This induces a substantial stress response, including an increase in corticosterone levels. Apoptosis in the spleen was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) with fluorescein-labeled dUTP. Flow cytometric analysis demonstrated a significant increase in the percentage of apoptotic cells in the spleen 2-6 h after administration of EtOH (3-6% apoptotic cells in treated mice vs 0.2-2% in controls). This increase was blocked by the glucocorticoid antagonist, RU 486, and administration of exogenous corticosterone in a manner that produced similar blood levels and kinetics as noted in EtOH-treated mice produced similar levels of apoptosis. Fluorescein-labeled Annexin V was used to confirm increased numbers of apoptotic cells in the spleen in EtOH-treated mice. These results indicate that stress-induced glucocorticoids are sufficient to induce apoptosis in the spleen, and this may be one mechanism by which stress responses cause immunosuppression.
Patterns of long-term survival following Ipilimumab (Ipi): the Memorial Sloan Kettering Cancer Center 10-year metastatic melanoma (MM) experience

Meeting abstracts In two Phase III randomized trials in MM, Ipi improved median overall survival (OS) [[1][1], [2][2]]. Here, we evaluate OS and characterize post-Ipi treatment patterns among long-term survivors from a single-institution cohort of patients (pts) treated with Ipi. Through a search
Barriers to Women in Management Careers: Confirmatory Factor Analysis of the Women as Managers Scale:

Stereotyping, prejudice, and discrimination serve as major barriers to women's career adjustment and advancement. To assess the current level of attitudes and the change in attitudes toward members of diverse populations in a variety of occupational roles, psychometrically sound assessment instruments are needed. The Women as Managers Scale is one such instrument. Exploratory factor and principle components analyses have been used in past research to challenge the dimensionality and reliability of the Women as Managers Scale. Confirmatory factor analyses revealed that a three-factor model was superior to a one-factor model, and was stable across subgroups. Evidence for discriminant validity among the factors was, however, weak. A possible explanation of the lack of discriminant validity is offered.
Comparison of responses by normal and deviant populations to Louisville Behavior Checklist.

Clinical assessment has been presented in the literature as involving extensive time and resources. Unfortunately, the realities of a comprehensive mental health clinic and private practice typical...
Using Duality to Solve Domain Equations

Abstract In this paper we show how the natural duality between the category CPOU of cpos and continuous mappings which are upper adjoints and the dual category CPOL of cpos and continuous lower adjoints leads to a simple proof that certain endofunctors preserve projective limits. This can be used to show such functors have invariant objects, which provide solutions to domain equations they define. In addition, we refine the results by applying them to subcategories of ALG, the category of algebraic cpos and continuous maps, and we also show how analogous results can be derived for the category CON of continuous cpos and continuous mappings.
3H-azidopine photoaffinity labeling of high molecular weight proteins in chloroquine resistant falciparum malaria.

Abstract Using 3H-azidopine, we have succeeded in labeling proteins from chloroquine resistant (CR) human falciparum malaria parasites in the molecular weight range of 155–170 Kd. Vinblastine does not compete, but azidopine blocks the labeling using 3H-azidopine. Relatively little or no labeling of the 155–170 Kd protein is seen in the chloroquine sensitive strain using 3H-azidopine. Further competition can be seen with nicardipine and reserpine (71%) respectively and verapamil (61%), chloroquine (48%), quinacrine (56%), trifluoperazine (32%) and chlorpromazine (33%). We speculate that this may be the glycoprotein responsible for the resistance to chloroquine in falciparum malaria.
Hydration properties of lens crystallins.

The water binding properties of bovine lens crystallins, α, βH, βL and low molecular weight (LMW), were investigated with different techniques. The water sorptive capacity was obtained in high vacuum sorption experiments volumetrically, and also gravimetrically in controlled atmosphere experiments. The two methods gave reproducible isotherms. The strongly sorbed water (bound water) was evaluated from the B.E.T. monolayer and from the values of isosteric heats. The bound water content of the crystallins were also measured by combined differential scanning calorimetry and thermogravimetric analysis. The non-freezable water contents calculated as % of the total water content and also as g g−1 crystallin, were used as an indicator for bound water. In all thre different techniques, the following order was obtained: βH > α > βL - LMW.
Using mobile agents as roaming security guards to test and improve security of hosts and networks

This paper discusses the design and implementation details of MAST (Mobile Agent-based Security Tool), a new mobile agent-based network security approach. MAST has been designed to support flexible and customizable network security tasks and training. This paper focuses on the implementation details and security aspects of MAST's components, services, and mobile-agent architecture
Investigating Discriminative Bail Setting: Multivariate Analysis on Louisiana Drug Interdiction

The core findings in the analyses of drug cases in traffic arrests on Louisiana's Interstate-10 were indicative of discriminative demographic profiling (Bowling, Ruiz, & Reynolds, 2008; Ruiz & Lee, 2009; Ruiz & Woessner, 2006). Assuming that a similar pattern would exist in the bail set by the court, the current study examined data collected directly from arrest reports between 1995 and 1996 located in the record room of the St. Martin Parish Sheriff's Office. The possible disparity in the bail across drug arrestees was tested using factorial analysis of variance and analysis of covariance and multiple regression analyses. Race was found to be a significant factor in discriminative bail setting. State of residence was also significantly related to the disparity, while gender was not found to be a correlate.
PARSUPPORT: A computer program for measuring the support of a party member for his party

number of actors (M) and majority outcomes (N); (3) the manner in which boundaries M and N are to be read in on data cards; and (4) the different voting options. Availability. VOTEPOW program deck can be obtained free of charge from New York University, Academic Computer Center, 725 Commerce Building, Washington Square, New York, New York 10003. All questions concerning the interpretations of VOTEPOW can be addressed to the authors of this report.
Chemically induced K+ conduction noise in squid axon.

Internal perfusion of tetraethylammonium ions (TEA) in squid axons produces a significant high frequency noise component. Although internal TEA suppresses the potassium conductance (G K) noise at relatively low frequencies, it induces high frequency noise which exceeds the intensity of the normal potassium and sodium noise. In addition, the induced noise is dependent on the presence of internal potassium ions (K+) suggesting that this source of noise arises from a modulation of the K+ conductance due to the blocking and unblocking of the K+ channel. The simplest model describing the TEA data is a two-step sequential pseudo-unimolecular reaction where TEA binds during an open conductance state. A unit channel conductance of 2 pS is estimated from the TEA data as well as noise induced by triethyldecylammonium (TEDA) ions. Thus, these data are consistent with the hypothesis that the channel is blocked whenever the quaternary ammonium ion binding site, located near or within the K+ channel, is occupied.
Decreasing Returns to Shareholders From R&D Spending in the Computer Industry

AbstractThis article explores the relationship between stockholder value changes and corporate research and development (R&D) spending in the computer industry. Researchers attempted to tie R&D expenditures and its various measurable effects to future results of the firms within an industry, with mixed results. They identify a positive, short-term relationship between stockholder share price movements and firm announcements of plans to increase R&D expenditures. They also show that industries with higher R&D intensities grow faster than those with low R&D intensities. However, little research is available that effectively relates R&D expenditures to future share price performance of the firms within an industry over a period of years. In this study, computer firm R&D intensity is correlated to future stockholder compound annual returns over both 1- and 5-year periods, based on research activity and financial results from 1992 to 1997. Results indicate a statistically significant negative relationship betw...
Site-Selection Fluorescence Spectrometry of Polycyclic Aromatic Hydrocarbons in Vapor-Deposited Argon Matrices

The use of tunable laser excitation to effect significant sharpening in the inhomogeneously-broadened fluorescence spectra of polycyclic aromatic hydrocarbons (PAHs) isolated in argon matrices at 15 K is reported. The broad-band-excited fluorescence spectra of most PAHs in solid argon exhibit complex multiplet structures assumed due to the location of individual PAH molecules in different types of discrete
Effects of design and operating variables on process characteristics in a methane discharge: a numerical study

A self-consistent two-dimensional radio frequency capacitively coupled glow discharge model has been developed in cylindrical coordinates for a methane discharge using a fluid model. The objective of the study is to identify the effects of design and operating variables of the reactor on the process characteristics such as the deposition rate, uniformity and the quality of the diamond-like-carbon film. The simulations provide insights to charged species dynamics and investigate their effects on the plasma process for a depositing methane discharge. The model includes continuity equations for electrons and positive and negative ions, and energy equation for electrons. Swarm data as a function of electron energy are provided as input to the model. The model predicts the electron density, ion density, and their fluxes and energies to the cathode. The roles of electrons, dominating ions and radicals in a capacitively coupled discharge are investigated. The radical and neutral densities in the discharge are calculated using a gas phase chemistry model. The diamond-like-carbon thin-film deposition rate is predicted using surface chemistry model. The gas phase chemistry model considers diffusion of radicals and neutrals along with creation and loss terms. The surface deposition/etching process involves adsorption-desorption, adsorption layer reaction, ion stitching, direct ion incorporation, etching and carbon sputtering. A systematic parametric study of plasma processing has been performed to identify process parameters to obtain better film deposition/etching on a wafer. The present work shows how plasma equipment simulation can be used for the practical investigation and optimization of a plasma-assisted chemical vapour deposition process. The simultaneous treatment of plasma dynamics and surface processes enables a very precise prediction of the process characteristics in terms of the film deposition rate, uniformity and the quality as functions of discharge control parameters and the reactor geometry.
Swirling and Double-Dipping: New Patterns of Student Attendance and Their Implications for Higher Education.

It is increasingly common for students to attend multiple institutions, and this involves more than transfer between institutions. Although sophisticated bureaucratic mechanisms for dealing with course-taking at other institutions have been developed, there is an urgent need to understand its educational implications and to develop ways to enhance educational coherence.
A cell-based immunobiosensor with engineered molecular recognition - Part II: Enzyme amplification systems

Abstract Immune cells in vivo routinely perform highly selective immunosensing in blood and tissues as part of their normal immune surveillance functions. We have been investigating the potential of exploiting the immunosensing detection abilities of excitable immune cells (i.e. the mast cell) for the development of whole cell immunobiosensors. A key feature is that these immune cells can be selectively engineered to recognize specific antigens in vitro . In the presence of antigen, these cells undergo excitable activation responses which result in increased metabolism and the exocytosis of stored intracellular mediators. We have previously determined that mast cell metabolic responses can be thermally transduced in real time, thus indicating the possibility of whole cell thermoelectric immunobiosensing. In this work we investigated the use of enzyme amplification systems to enhance the direct transduction of immune cell responses to analyte. It was found that with appropriate enzymes, peak outputs occurred within ∼ 5 min (4–20 times faster than without enzymes) and peak response magnitudes were up to nine-fold greater than without enzymes.
Development and testing of 100 kW/1 min Li-ion battery systems for energy storage applications

Two 100 kW min{sup -1} (1.67 kW h{sup -1}) Li-ion battery energy storage systems (BESS) are described. The systems include a high-power Li-ion battery and a 100 kW power conditioning system (PCS). The battery consists of 12 modules of 12 series-connected Saft Li-ion VL30P cells. The stored energy of the battery ranges from 1.67 to 14 kW h{sup -1} and has an operating voltage window of 515-405 V (dc). Two complete systems were designed, built and successfully passed factory acceptance testing after which each was deployed in a field demonstration. The first demonstration used the system to supplement distributed microturbine generation and to provide load following capability. The system was run at its rated power level for 3 min, which exceeded the battery design goal by a factor of 3. The second demonstration used another system as a stand-alone uninterrupted power supply (UPS). The system was available (online) for 1146 h and ran for over 2 min.
Experimental Tests of Truss Bridge Gusset Plate Connections with Sway-Buckling Response

The collapse of the Interstate 35W bridge in Minneapolis, Minnesota, in 2007 brought into question the strength of large-size gusset plates in steel truss bridges. To provide new data on the behavior and strength of large-size bridge-type gusset plates, experimental tests were performed and are described in this paper. The research program focused on sway-buckling behavior and test variables included plate thickness, compression diagonal flexural stiffness, initial out-of-plane imperfection, and member load combinations. Unique to this test program was the direct consideration of different compression diagonal out-of-plane flexural stiffnesses on plate buckling behavior and capacity. Results showed that sway-buckling behavior and ultimate capacity were affected by initial out-of-plane imperfections of the plate and the out-of-plane bending stiffness of the truss compression diagonal. Results also showed that the effective length factor, K, a parameter used in present load rating guides, did not accurately predict sway-buckling capacity, and the Whitmore section approach may not be the best approximation for use in plate sway-buckling behavior. A stepped-column approach was shown to illustrate and predict the effect of the plate-member stiffness interaction on buckling capacity.
Criteria for the design of manipulator arms for a high stiffness-to-weight ratio

Abstract Design aspects of a six degree-of-freedom high-accuracy manipulator are presented. The manipulator arm (called the UTI-arm) comprises four revolute and two prismatic joints. The mechanical design of the manipulator is aimed at obtaining high accuracy and a high stiffness-to-weight ratio of the links. Prestressing of mechanical elements is performed to transform strength to stiffness. Design of links under tension load is carried out to enhance bending stiffness. In the past, researchers have reported inefficiency of prismatic joints due to their high compliance. Compared to a uniform thin-walled tube, prismatic joints used in this design provide an isotropic, higher bending stiffness with a relatively low loss in torsional stiffness. Experiments were conducted to verify the theory presented for calculating torsional stiffness of such joints. A finite element model was also used to validate the model. The mechanical design of the arm is presented in detail in view of the proposed prismatic joint cross section and the prestressing effects.
Biologic effects of short-term phenobarbital treatment on the response to vitamin D and its metabolites in the chick.

Abstract The action of cholecalciferol (vitamin D3) (D3) and two of its active metabolites, 25-hydroxy-cholecalciferol (25-OH-D3) and 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3), was studied in phenobar-bital-treated and untreated rachitic chicks by means of a bioassay for intestinal calcium absorption and bone resorption. Phenobarbital treatment (7 days) reduced the ability of single doses (0.65 to 3.5 nmoles) of D3 and 25-OH-D3 to stimulate intestinal calcium absorption and bone resorption. The impaired biological responses to these moderate doses of D3 could be overcome by increasing the dose (32.5 nmoles). In contrast, administration of small doses of 1,25-(OH)2-D3 (0.26 nmole) stimulated both the intestinal calcium transport and bone resorption responses in phenobarbital-treated chicks. Moreover, phenobarbital treatment appeared to enhance the calcemie response of bone to 1,25-(OH)2-D3. The metabolism of radioactive D3 was also studied in control rachitic chicks and rachitic chicks treated with phenobarbital for 7 days. Sephadex LH-20 column chromatography of lipid-soluble extracts of blood, intestinal mucosa and bone was carried out 24 hr after administration of a single dose of 4-14C-vitamin D3. The anticonvulsant treatment resulted in markedly lower quantities of 1,25-(OH)2-D3 in the bone, but with no major changes in the amount of this steroid present in the intestine. The drug treatment also resulted in increased amounts of D3 and 25-OH-D3 in the blood and intestinal mucosa. Seven-day anticonvulsant treatment of the rachitic chick clearly impairs the biological responses to D3 and also alters its metabolism. It is possible that the reported high incidence of osteomalacia occurring in patients on long-term anticonvulsant therapy may possibly be caused by derangements in the conversion of D3 to its biologically active metabolites and in their association with the target tissues. This may provide some explanation for the disruption of normal calcium metabolism which occurs after chronic administration of phenobarbital and other related drugs.
Administrative Reform as Credible Commitment: The Impact of Autonomy on Revenue Authority Performance in Latin America

Abstract During the past decade, diverse developing countries have introduced radical reforms in their collection of taxes. In more than 15 countries traditional tax departments have been granted the status of semi-autonomous revenue authorities (ARAs). This paper investigates the design and impact of ARAs in Latin America, arguing that politicians create ARAs in order to signal a credible commitment to taxpayers that tax administration will be more effective, fair, and competent. Using survey data from corporate taxpayers and tax professionals in Bolivia, Mexico, Peru, and Venezuela, the paper presents econometric analyses and performance indicators that support the hypothesis that there is a link between perceptions of credibility, performance, and agency autonomy.
Scanning Thermoacoustic Tomograhy in Biological Tissue

Thermoacoustic tomography in the microwave region is explored to image biological tissue. When short-pulse electromagnetic energy is deposited into tissue, acoustic waves are generated due to thermoelastic expansion. The microwave-induced acoustic wave is detected with a focused ultrasonic detector. Each time-domain signal from the ultrasonic transducer represents a one-dimensional image along the acoustic axis. Scanning the system generates multi-dimensional images. The time-domain acoustic signal was simulated theoretically and measured experimentally, where the theoretical and experimental results were in good agreement. Two-dimensional tomographic images of biological tissue were obtained experimentally. Thermoacoustic tomography combines the advantage of microwaves in imaging contrast and the advantage of acoustic waves in imaging resolution.
Experimental investigation of controlled microdroplet evaporation toward scalable micro/nanomanufacturing

This article focuses on an experimental investigation of microdroplet evaporation as a step toward developing a scalable droplet-based micro/nanomanufacturing process. A customized direct-write inkjet setup is utilized to generate monodisperse microdroplets for two fluid types (acetone and distilled water). The microdroplet evaporation dynamics was studied using a light-emitting diode strobe-based high-speed photography. The microdroplet was heated using convective heat transfer via a resistive heating ring fixture that controlled the heat flux. The effect of nozzle size and fluid type on microdroplet size reduction was investigated. The output responses include percentage volume reductions, drop size shrinkage, and changes in the surface-to-volume ratio. The experimental results were validated with an equivalent theoretical model and close agreement between the results was obtained. This research provides a basic understanding of the evaporation dynamics of microdroplets and is a precursor toward their t...
A New Vacuum-Assisted Probe for Minimally Invasive Radiofrequency Ablation

Purpose The Cobra Adhere XL (Estech, San Ramon, CA) is a multiple-electrode, temperature-controlled, monopolar radiofrequency probe with a vacuum-assisted stabilization system. We evaluated this new technology for epicardial ablation of atrial fibrillation in mitral valve patients through a right mini-thoracotomy. Description Between June and August 2008, 12 patients underwent minimal invasive surgery for mitral disease and ablation for atrial fibrillation with the Cobra Adhere XL (Estech). Three patients had paroxysmal atrial fibrillation. Off-pump pulmonary vein isolation was performed with an epicardial oval lesion parallel to the mitral plane. In 10 patients, an endocardial lesion to the mitral annulus was added. Evaluation There were no operative deaths or major postoperative complications. At a mean follow-up of 8.76 ± 1.0 months, 11 patients (91.67%) were in stable sinus rhythm. Echocardiography underscored a complete recovery of atrial transport function in most of these patients (90.91%). No major cardiac and cerebrovascular events occurred during follow-up. Conclusions Left-side ablation combined with minimally invasive surgery for mitral disease can be easily, safely, and effectively performed with the Cobra Adhere XL probe.
The biology of pro-thyrotropin-releasing hormone-derived peptides.

I. Introduction II. Biosynthesis of TRH and Other pro-TRH-Derived Peptides A. Biosynthesis and processing of pro-TRH B. Intracellular sites of pro-TRH processing C. Tissue-specific processing of pro-TRH D. The role of PCs and CPs E. Neuropeptide and catecholamine regulation of Pro-TRH biosynthesis and processing F. Glucocorticoids modulate the biosynthesis and processing of pro-TRH G. Leptin regulates pro-TRH biosynthesis III. Function of TRH A. The HPT axis B. Extrahypophysiotropic TRH IV. Function of non-TRH pro-TRH-Derived Peptides A. prepro-TRH160–169 (pST10) B. prepro-TRH178–199 (pFE22) C. prepro-TRH178–185 and prepro-TRH186–199 (pFQ7 and pSE14) D. prepro-TRH53–74 (pFT22) E. prepro-TRH83–106 (pEH24) and prepro-TRH208–255 F. TRH-Gly V. Non-TRH pro-TRH-Derived Peptides Outside of the CNS VI. TRH and Other pro-TRH-Derived Peptide Receptors A. The TRH receptor B. The prepro-TRH160–169 (pST10) receptor VII. TRH Degradation VIII. Concluding Remarks
New high-speed cell sorting methods for stem cell sorting and breast cancer cell purging

An important problem in clinical medicine is that of positively selecting hematopoietic stem cells or mobilized peripheral blood stem cells for autologous bone marrow transplantation while purging it of contaminating tumor cells. Since both the stem cells to be positively selected and the tumor cells to be purged are relatively rare cells, this poses special problems for their isolation in terms of purity and yield of stem cells, with a high penalty of misclassification for contaminating tumor cells. A model system of tumor cells spiked into bone marrow or blood cells was used to validate the system. Multiparameter data mixtures of human MCF-7 breast cancer cells and human peripheral blood or bone marrow cells were first analyzed by discriminant function analysis. Mathematical methods were developed to assess the relative probabilities of misclassification. Cell identification tags, implemented as additional correlated listmode parameters not used for these analyses, were used to uniquely identify each cell type and to compare classifier results. The performance of classifier systems was also assessed using ROC (`receiver operating characteristics') analysis. Then the classification system was implemented using lookup tables allowing for real-time (in this system approximately 625 microseconds) rapid separation of these cell types. Isolated cell types, purities and yields were assessed by single-cell PCR molecular characterizations.
EASY CASES AND VALUE INCOMMENSURABILITY

Several critics have denied value incommensurability - or the claim, roughly, that there is no common measure in terms of which values can be weighed - on the basis of what we might call the argument from easy cases. Although the argument from easy cases is quite popular, what is much less often discussed is what exactly the argument entails - in other words, what sort of further commitments the argument generates. Suppose we grant that easy cases point to the existence of a common measure. How then should we think about this common measure? What is its scope? How widely does it range? I attempt to clarify these questions and in the process evaluate the force of the argument from easy cases.
Ion-Exchange Separation and Ultraviolet Spectrophotometric Determination of Dextromethorphan in Pharmaceutical Products

A method for the isolation and determination of dextromethorphan is presented. The dextromethorphan is extracted with strong cation exchange resin, AG 50W-X4, and is subsequently eluted with 1 N hydrochloric acid in 60 per cent methanol in water. The dextromethorphan is determined in the eluate by ultraviolet spectro-photometry. The assay is used successfully on several commercial products.
The paradox of digital preservation

Preserving digital information is plagued by short media life, obsolete hardware and software, slow read times of old media, and defunct Web sites. Herein lies the paradox: we want to maintain digital information intact, but we also want to access this information in a dynamic use context. Failure to address digital preservation problems is analogous to squandering potential professional, personal and economic gains, contributing to cultural and intellectual poverty and resulting in exorbitant costs for recovery. We are compelled to meet the research challenge to resolve the conflict between the creation context and the use context to facilitate digital information preservation.
Micromechanical Simulation of the Deformation and Fracture of Polymer Blends

We couple morphological studies of binary, immiscible blends with mechanical studies of deformation and fracture to determine the influence of the blend composition on the initiation and propagation of cracks in polymeric materials. The Cahn−Hilliard (CH) method is employed to simulate the structural evolution of the molten AB blend. We assume that the material undergoes a rapid quench to yield a solid whose microstructure is given by the CH approach. The output from these CH simulations serves as the input to a dynamic lattice spring model (LSM), a micromechanical model that consists of a three-dimensional network of springs, which connect regularly spaced mass points. Within the LSM, the A and B phases, as well as the interfacial regions, are assigned distinct spring constants, thereby allowing us to model a blend of a compliant and a stiff polymer. With the application of a tensile deformation, the heterogeneous microstructures give rise to complex local elastic fields. Using an energy-based fracture c...
Expanding Role of G Proteins in Tight Junction Regulation: Gαs Stimulates TJ Assembly☆

Abstract Multiple signaling mechanisms regulate epithelial cell tight junction (TJ) assembly and maintenance. Several G proteins are likely to regulate these processes, but only Gi/o have been specifically tested. Treatment of MDCK cells with cholera toxin, a Gαs activator, accelerated TJ development in the calcium switch as measured by the time to half-maximal [T50 (H)] transepithelial resistance (TER). Gαs was predominantly localized in the lateral membrane, but a fraction colocalizes with ZO-1 in the TJ. MDCK cell lines expressing epitope-tagged Gαs and constitutively active (R201Cαs) showed a similar localization. TJ assembly was significantly faster in R201Cαs-MDCK cell lines (T50 (H) of 1.7 versus 3.3 h for controls) without detectable differences in cAMP levels. Confocal studies showed R201Cαs-MDCK cells more rapidly localized ZO-1 and occludin into the developing TJ without affecting E-cadherin or Na+/K+ ATPase localization. Endogenous Gαs and R201Cαs were immunoprecipitated with ZO-1 at baseline and during TJ assembly. The data supports a model of multiple Gα subunits interacting with TJ proteins to regulate the assembly and maintenance of the TJ.
Development of GABAA receptors on medial septum/diagonal band (MS/DB) neurons after postnatal ethanol exposure

Abstract The impact of `binge-like' ethanol exposure on postnatal days (PD) 4–9 was examined on development of γ-aminobutyric acid type A receptors (GABA A R) during the first month of life in the rat. Whole-cell patch-clamp recordings in acutely isolated medial septum/diagonal band (MS/DB) neurons were used to define effects of rapidly applied ethanol and other allosteric modulators on bicuculline-sensitive GABA currents. Three age groups were examined including `pups' (PD 4–10), `juveniles' (PD 11–16) and `young adults' (PD 25–35). In untreated neurons, maximum responses to GABA and the apparent GABA EC 50 increased ∼2-fold during the first month of life. Potentiation of GABA responses by pentobarbital, midazolam, and loreclezole all increased with age, while Zn 2+ inhibition declined. Initial inhibition by ethanol switched to potentiation of GABA responses during this time. In vivo, binge-like ethanol treatment (4.5 g kg −1 day −1 divided into two doses, 2 h apart on PD 4–9) reduced both the GABA maximal response and GABA EC 50 measured on PD 11–16. These measures returned to control levels by PD 25–35. After binge-like postnatal ethanol exposure, age-dependent loss of Zn 2+ inhibition of GABA responses was increased, while potentiating actions of in vitro ethanol were blocked. GABA A R modulation by other drugs was unaffected. These data suggest that early postnatal ethanol exposure disrupts the expected developmental pattern of GABA A R function in MS/DB neurons, an action that could contribute to neurobehavioral deficits associated with the fetal alcohol syndrome. Whether these changes are due to cellular damage, delayed gene expression or post-translational modification needs to be determined.
Microbiological Quality of Restructured and Conventional Steaks Manufactured from Electrically Stimulated Hot‐ and Cold‐Boned Carcasses

The microbiological quality of restructured beef steaks was compared with that of conventional loin steaks. Restructured and conventional steaks were sampled before and after assignment to either a fresh meat overwrap (oxygen permeable) storage treatment for 1 wk or to vacuum packaged storage treatments for 1, 3 or 6 wk. Microbial counts were higher (P < 0.01) in restructured steaks than in conventional steaks. Except for Enterobacteriaceae and staphylococci counts, higher counts were observed for steaks from hot-boned sides than for steaks from cold-boned sides. Counts tended to be lower (P <0.01) for vacuum packaged steaks after 1 wk than for steaks packaged in oxygen permeable film. Aerobic, anaerobic, psychrotrophic, and lactobacilli counts increased (P < 0.01) for vacuum packaged steaks throughout the storage period.
Secondary fragmentation of the solar and heliospheric observatory sungrazing comets at very large heliocentric distance

The temporal distribution of the Kreutz group of sungrazing comets has been known to have an episodic character on timescales from weeks to tens of years. With the large number of minor members of this group being nowadays discovered in images taken with the Solar and Heliospheric Observatory coronagraphs, it has become apparent that the distribution of these faint comets is episodic on a much shorter timescale, with objects arriving in pairs during a small fraction of a day. It is shown that the rate of these pairs is much too high for a random sample. Their existence is readily explained as a result of secondary, low-velocity, nontidal fragmentation episodes, which occur virtually spontaneously at very large heliocentric distances and involve the products of near-perihelion splitting of progenitor fragments during their previous return to the Sun. In fact, the pairs are merely extreme manifestations of larger clusters of such subnuclei, with a complex hierarchy of fragments. Each cluster is an outcome of a sequence of nontidal fragmentation events, which begins—after the initial tidal breakup—at some point along the outbound leg of the orbit and then continues episodically to and past aphelion. A similar scenario of posttidal progressive disintegration was firmly established for comet Shoemaker-Levy 9, based on extensive observations of its secondary and tertiary nuclei during many months preceding the comet's collision with Jupiter. Also, there are similarities with the mechanism proposed recently for the formation of striations in the dust tail of comet Hale-Bopp, and a logical extension of this process is the evolution of comet dust trails.
Membrane Tetraheme Cytochrome cm552 of the Ammonia-Oxidizing Nitrosomonas europaea: A Ubiquinone Reductase

Cytochrome cm552 (cyt cm552) from the ammonia-oxidizing Nitrosomonas europaea is encoded by the cycB gene, which is preceded in a gene cluster by three genes encoding proteins involved in the oxidation of hydroxylamine: hao, hydroxylamine oxidoreductase; orf2, a putative membrane protein; cycA, cyt c554. By amino acid sequence alignment of the core tetraheme domain, cyt cm552 belongs to the NapC/TorC family of tetra- or pentaheme cytochrome c species involved in electron transport from membrane quinols to a variety of periplasmic electron shuttles leading to terminal reductases. However, cyt cm552 is thought to reduce quinone with electrons originating from HAO. In this work, the tetrahemic 27 kDa cyt cm552 from N. europaea was purified after extraction from membranes using Triton X-100 with subsequent exchange into n-dodecyl β-d-maltoside. The cytochrome had a propensity to form strong SDS-resistant dimers likely mediated by a conserved GXXXG motif present in the putative transmembrane segment. Optical s...
Alpha‐Chloralose Anesthesia Inhibits the Somato‐Sympathetic Reflex Response in Cats More Effectively than Halothan

Summary The effect of halothane anesthesia (H; 0. 8 Vol%) or alpha-chloralose anesthesia (AC; 60mg/kg i. v.) on the somato-sympatho-adrenal reflex response evoked by supramaximal bilateral sciatic nerve stimulation, were examined in two groups of cats (H: n = 6; AC: n = 4). Blood samples were collected simultaneously from the adrenal vein and femoral artery at baseline (SI) and during bilateral sciatic nerve stimulation (S2) for the measurement of norepinephrine, epinephrine, neuropeptide Y, and Metenkephalin, while mean arterial blood pressure (MABP) and heart rate (HR) were recorded. There were no differences between groups at baseline. In halothane anesthetized cats, sciatic nerve stimulation caused significant increases in MABP (SI: 113 ± 8 mm Hg, S2: 178 ± 10mm Hg; mean ± SE), HR (SI: 223 ± 15bpm, S2: 278 ± 22bpm), and adrenal vein plasma levels of norepinephrine (SI: 3. 1 ± 0. 98 ng/ml, S2: 19. 53 ± 11. 5ng/ml), epinephrine (SI: 15. 5 ± 4. 76ng/ml, S2: 67. 31 ± 14. 9ng/ml), neuropeptide Y (SI: 1. 3 ± 0. 12ng/ml, S2: 2. 16 ± 0. 42 ng/ml), and Met-enkephalin (SI: 107 ± 35. 7pg/ ml, S2: 200 ± 76. 5pg/ml). In contrast, sciatic nerve stimulation in alpha-chloralose anesthetized cats, caused a significant increase only in MABP during sciatic nerve stimulation (SI: 115 ± 10mm Hg, S2: 171 ± 7 mm Hg), while HR and adrenal vein plasma levels of catecholamines, neuropeptide Y and Metenkephalin remained unchanged from baseline. Adrenal vein epinephrine levels measured during stimulation in the alpha-chloralose group (S2: 6. 17 ± .86 ng/ml), were significantly lower as compared to values observed during halothane anesthesia. These data clearly demonstrate inhibitory effects of alpha-chloralose on the somato-sympathetic reflex response, which may reflect a central analgesic effect of this drug. A light level of halothane anesthesia seems to be more appropriate than alpha-chloralose for cat experiments examining sympatho-adrenal responses.
14C analysis via intracavity optogalvanic spectroscopy

A new ultra sensitive laser-based analytical technique, intracavity optogalvanic spectroscopy (ICOGS), allowing extremely high sensitivity for detection of (14)C-labeled carbon dioxide has recently been demonstrated. Capable of replacing accelerator mass spectrometers (AMS) for many applications, the technique quantifies zeptomoles of (14)C in sub micromole CO(2) samples. Based on the specificity of narrow laser resonances coupled with the sensitivity provided by standing waves in an optical cavity, and detection via impedance variations, limits of detection near 10(-15 14)C/(12)C ratios have been obtained with theoretical limits much lower. Using a 15 W (14)CO(2) laser, a linear calibration with samples from 5 x 10(-15) to >1.5 x 10(-12) in (14)C/(12)C ratios, as determined by AMS, was demonstrated. Calibration becomes non linear over larger concentration ranges due to interactions between CO(2) and buffer gas, laser saturation effects and changes in equilibration time constants. The instrument is small (table top), low maintenance and can be coupled to GC or LC input. The method can also be applied to detection of other trace entities. Possible applications include microdosing studies in drug development, individualized sub therapeutic tests of drug metabolism, carbon dating and real time monitoring of atmospheric radiocarbon.
Duodenal gangliocytic paraganglioma: a radiological-pathological correlation

Duodenal gangliocytic paraganglioma is a rare tumor that characteristically occurs in the second portion of the duodenum and typically presents with gastrointestinal bleeding. Gangliocytic paragangliomas have a characteristic triphasic microscopic appearance with epithelioid cells, spindle cells, and ganglion cells, resulting in a complex histology with features of paraganglioma, carcinoid, and ganglioneuroma. Duodenal gangliocytic paragangliomas have an excellent prognosis after surgical resection but metastatic spread to regional lymph nodes and recurrence may rarely occur. We report a case of duodenal gangliocytic paraganglioma and discuss the radiological and pathological differential diagnosis of this rare entity.
Role of a solvent-exposed aromatic cluster in the folding of Escherichia coli CspA.

Escherichia coli CspA is a member of the cold shock protein family. All cold shock proteins studied to date fold rapidly by an apparent two-state mechanism. CspA contains an unusual cluster of aromatic amino acids on its surface that is necessary for nucleic acid binding and also provides stability to CspA (Hillier et al., 1998). To elucidate the role this aromatic cluster plays in the determining the folding rate and pathway of CspA, we have studied the folding kinetics of mutants containing either leucine or serine substituted for Phe18, Phe20, and/or Phe31. The leucine substitutions are found to accelerate folding and the serine substitutions to decelerate folding. Because these residues exert effects on the free energy of the folding transition state, they may be necessary for nucleating folding. They are not responsible, however, for the very compact, native-like transition state ensemble seen in the cold shock proteins, as the refolding rates of the mutants all show a similar, weak dependence of unfolding rate on denaturant concentration. Using mutant cycle analysis, we show that there is energetic coupling among the three residues between the unfolded and transition states, suggesting that the cooperative nature of these interactions helps to determine the unfolding rate. Overall, our results suggest that separate evolutionary pressures can act simultaneously on the same group of residues to maintain function, stability, and folding rate.
Starting at the beginning: the neuropsychological status of children with new-onset epilepsies

This review examines the neurodevelopmental contribution to the cognitive and behavioural complications of epilepsy. Following a brief review of the lifespan complications of childhood epilepsies, attention turns to cognitive, psychiatric and social correlates of childhood epilepsies reported in population-based and tertiary care studies. The focus then becomes the neurobehavioural status of children with new-onset epilepsy; a point in time not confounded by the effects of years of recurrent seizures, medications, and social reactions to epilepsy. Recent research shows that abnormalities in cognition, brain structure and behaviour are present at or near the time of diagnosis. Further, careful history taking indicates that neurobehavioural problems may be present in advance of the first seizure suggesting the potential influence of epileptogenesis, antecedent neurodevelopmental abnormalities, genetic and environmental susceptibilities, and other risk factors. This becomes the substrate upon which to characterise the effects of epilepsy and its treatment on subsequent neurodevelopment. The review concludes with suggestions for future clinical care and research.