cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 14385: c-Src Tyrosine Kinase Mediates the Effect of Mitochondrial Oxidative Stress on Gap Junctional Remodeling and Ventricular Tachycardia

Introduction: Reactive oxygen species (ROS) are thought to play a central role in the genesis of arrhythmia. Mitochondria are the major source of cardiac ROS. Studies suggest ROS activates c-Src tyrosine kinase, which reduces Cx43 at the gap junctions by competing with Cx43 for binding to Zonula Occludence-1. We sought to determine the role of mitochondria oxidative stress in the genesis of ventricular arrhythmia in a manganese superoxide dismutase (MnSOD) knock out mouse model. We hypothesized that excess ROS in this model would activate c-Src and reduce Cx43 levels and that inhibition of c-Src would prevent Cx43 remodeling and the risk of arrhythmia. Method: Wild type and MnSOD+/- mice with and without treatment with the c-Src inhibitor PP1 (1.5 mg/kg IP three times/week x 2 weeks) were studied. Western blotting and immunohistochemistry staining for Cx43 were performed. Mitochondrial ROS was measured by confocal microscopy and flow cytometry from isolated cardiomyocytes using mitoSOX red. In-vivo epicardial mapping was performed using a 30-channel bipolar electrode array with 1 mm resolution. Results: MnSOD+/- myocytes showed a 66% increase in the level of mitochondrial ROS compared to the control (by mitoSOX, P Conclusion: Mitochondrial oxidative stress is associated with increased risk of ventricular arrhythmia and a significant reduction in Cx43 at the gap junctions, providing the impaired conduction substrate for reentry arrhythmia. c-Src tyrosine kinase seems to mediate the effect of mitochondrial ROS on Cx43 and may be an effective antiarrhythmic target in oxidative stress states.
Early Cognitive and Adaptive Functioning of Clinically Referred Infants and Toddlers with Cancer

Many children with cancer are diagnosed during infancy and toddlerhood (< 3 years of age), potentially resulting in disrupted and/or missed developmental opportunities. Our objective was to describe the functioning of infants and toddlers with cancer who were clinically referred for evaluation at a hospital-based psychology clinic. Data from 29 very young children with cancer (Mage = 23.62 ± 6.6 months; 55.2% male) who completed clinically referred assessments from 2010 to 2015 were abstracted. Children were 11.3 months post-diagnosis (SD = 7.77, range 1–29 months) with just over half off-therapy at the time of assessment (55.2%). Overall, developmental functioning was significantly below expectations [t(22) = − 8.99, p < .001]. Adaptive functioning [t(25) = − 6.41, p < .001] was also significantly below expectations. Infants and toddlers with cancer appear to be at significant risk for weaknesses in early cognitive and adaptive functioning. The margin of deficits found in this study warrant the need for further investigation and consideration of this young population to ensure optimal functional development.
Electronic Cigarette Companies’ Twitter Messages: Public Interest (Mis)communication

Despite increased controversies over the health effects of electronic cigarettes (e-cigarettes), little is known about how the public interest issue has been discussed by e-cigarette companies on social media. Using arguments from the theory of planned behavior as a guide, this study examines how e-cigarette companies engage with potential customers on Twitter. Using quantitative content analysis, this study examined 525 tweets from the top five e-cigarette companies that occurred between July 9, 2016, and September 9, 2016, one month before and after the U.S Food and Drug Administration implemented a new regulation limiting sales and distribution of tobacco products to minors. Results indicate that the deeming did not affect e-cigarette companies’ message strategies on Twitter. Theoretical and practical applications for public interest communications are discussed.
Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones.

The solution- and solid-state interactions between the octadentate siderophore mimic 3,4,3-LI(1,2-HOPO) (343HOPO) and group IV metal ions were investigated using high-resolution mass spectrometry, liquid chromatography, UV-visible spectrophotometry, metal-competition batch titrations, and single crystal X-ray diffraction. 343HOPO forms a neutral 1 : 1 complex, [HfIV343HOPO], that exhibits extreme stability in aqueous solution, with a log β110 value reaching 42.3. These results affirm the remarkable charge-based selectivity of 343HOPO for octacoordinated tetravalent cations with a Hf(IV) complex 1021 more stable than its Lu(III) analogue. Moreover, [HfIV343HOPO] and its Zr(IV) counterpart show exceptional robustness, with the ligand remaining bound to the cation over a very broad pH range: from pH ∼ 11 to acidic conditions as strong as 10 M HCl. In stark contrast, Ti(IV)-343HOPO species are far less stable and undergo hydrolysis at pH as low as ∼6, likely due to the mismatch between the preferred hexacoordinated Ti(IV) ion and octadentate 343HOPO ligand. The extreme charge-based and denticity-driven selectivity of 343HOPO, now observed across the periodic table, paves the way for new selective sequestration systems for radionuclides including medical 44Ti, 89Zr or 177Lu/Hf isotopes, toxic polonium (Po) contaminants, as well as rutherfordium (Rf) research isotopes. Furthermore, despite the lack of a chiral center in 343HOPO, its complexes with metal ions are chiral and appear to form a single set of enantiomers.
Guantanamo's Greatest Hits: The Semiotics of Sound and the Protection of Performer Rights Under the Lanham Act

As Bruce Springsteen and Ronald Reagan, Jackson Browne and John McCain, and Tom Morello and Paul Ryan can attest, the exploitation of creative works for political or commercial purposes that run contrary to artists’ ideals can stir passions and trigger lawsuits. Yet for performers who are not authors of the exploited works, there is little meaningful legal relief provided by the federal Copyright Act. Instead, such performers — from featured singers and dancers to actors and other personalities known for their distinctive traits — have leaned on alternative theories for recovery, thereby raising the specter of liability outside of copyright law for such unwelcome uses. While a rich body of literature analyzes and critiques the use of publicity rights in these contexts, the vindication of performer rights through the Lanham Act and related state law has received far less attention. Using musical efforts to addle Guantanamo Bay detainees as a launching point, this Article seeks to address this void by analyzing and critiquing performers’ efforts to seek relief under the Lanham Act and related state law for such unwanted uses of their creative output. Though courts in such cases have frequently ruled in tandem on right of publicity and trademark/false endorsement claims, jurists and scholars have given insufficient independent analysis to the particularities of the latter. The result is a series of decisions on performance characteristics — from the vocal (a gruff, raspy voice a la Tom Waits) to the physical (a blonde donning jewelry and a gown flipping large block letters a la Vanna White or a stout middle-aged man drinking beer while seated at the end of a bar a la Cheers) — that take seemingly paradoxical and troubling positions. Inconsistencies as to what constitutes a protectable mark and whether a likelihood of confusion occurs from the use of said mark have plagued the case law and have threatened to undermine the functioning of the marketplace for licensing creative works and burden the copyright regime as a whole. The Article concludes by considering potential alternatives for redressing performer concerns in a manner that better protects the public domain and balance in the intellectual property regime.
An approach to Dermatopathology: Immunohistochemical and special stains

Interpreting pathology specimens is important to the diagnosis of dermatologic disease. This chapter highlights a basic approach to viewing a specimen and understanding important descriptive terminology, immunoperoxidase stains, special stains, and immunofluorescent studies in dermatology.
Effects of Surface Compliance on Shock Boundary Layer Interaction in the Caltech Mach 4 Ludwieg Tube

Understanding the effects of fluid-structure interactions caused by turbulent boundary layers and shock boundary layer interactions, on thin, compliant, structures is crucial for developing light-weight, reusable, high-speed vehicles. In this work, flow structures in a Mach 4 boundary layer are first studied over i) rigid flat plates to establish a baseline and ii) statically deformed geometries to investigate the flow response to surface deformation over longer time scales. Next, the flow response over a compliant steel panel under static and dynamic loading from an oscillating shock generator is investigated. Euler simulations are performed to design the geometry and location of the shock generator in the Caltech Mach 4 Ludwieg tube test section, predict the amplitude of the oscillation required to drive the pressure wave across the compliant surface, and to calculate the pressure rise on the compliant surface due to the dynamic load. Schlieren video, fast response pressure sensitive paint profiles, and laser displacement sensor measurements of the response of a 0.2 mm thick steel panel to loading from the shock generator are discussed and compared to similar measurements of the rigid case. The compliant panel center point deforms by nearly 4 panel thicknesses under these conditions and results in a flattened and elongated separation region at the interaction location and lower static pressure on the panel surface when compared to the rigid panel case.
A nucleobase cation symporter 2, EaXanP, from Erwinia amylovora transports xanthine

Erwinia amylovora causes fire blight, one of the more serious diseases for apple and pear cultivation. Previous studies generated E. amylovora mutants in purine metabolic pathway that still retain the ability to grow on host tissue and produce limited disease symptoms. Here we show that the E. amylovora genome has a locus that encodes for a xanthine permease belonging to the nucleobase cation symporter 2 (NCS2) family and the encoded protein displays a high level of amino acid sequence similarity to the Escherichia coli XanP. Our hypothesis is to investigate if the lack of a xanthine transporter has an effect upon disease progression. Heterologous expression of EaXanP in nucleobase transporter-deficient E. coli strains, coupled with radiolabeled nucleobase uptake studies determined that EaXanP is a high affinity xanthine transporter with a Km of 1.2 μM + 0.1 μM that confers sensitivity to growth on caffeine (1,3,7-trimethylxanthine). An E. amylovora ΔxanP::Camr mutant shows resistance to growth on caffeine, while over expression of EaXanP increases growth sensitivity to caffeine. While the EaXanP gene is expressed in infected immature pear fruitlets, an E. amylovora xanthine transport mutant is still able to grow and cause disease symptoms on immature pears and apple fruitlets.
Device Characterization of a Sulfur-Implanted p $^{++}$ /p GaSb Photovoltaic Camel Diode

The implantation and rapid thermal annealing of sulfur (S+) ions has previously been shown to be an effective method in non-epitaxially attaining hole carrier concentrations as high as $1\times {10^{19}} \; \rm cm^{-3}$ in gallium antimonide (GaSb). This technique was used to fabricate a photovoltaic diode by delta-doping the front surface of a p-type GaSb substrate and forming a p++/p junction. The steep potential created using this process is increased by strong Fermi level pinning at the metal/p++ interface, resulting in a camel diode with a barrier height of 0.51 eV. A post-fabrication etch process succeeded in improving the short circuit current density to 41.8 mA/cm $^2$ and the internal quantum efficiency to 90% by enhancing the carrier lifetime away from the front metal contact grid. Likewise, the open circuit voltage improved to 0.21 V, with an intrinsic fill factor above 40%. These results offer the potential of a significantly higher power output than similar non-epitaxial devices made on n-type GaSb substrates.
A Multistaged Hyperparallel Optimization of the Fuzzy-Logic Mechanistic Model of Molecular Regulation

MotivationAlthough it circumvents hyperparameter estimation of ordinary differential equation (ODE) based models and the complexities of many other models, the computational time complexity of a fuzzy logic regulatory model inference problem, particularly at higher order of interactions, quickly approaches those of computationally intractable problems. This undermines the benefits inherent in the simplicity and strength of the fuzzy logic-based molecular regulatory inference approach. ResultsFor a sample inference problem - molecular regulation of vorinostat resistance in the HCT116 colon cancer cell lines, our modeled, designed and implemented "multistaged-hyperparallel" optimization approach significantly shortened the time to model inference from about 485.6 hours (20.2 days) to approximately 9.6 hours (0.4 days), compared to an optimized version of a previous implementation. AvailabilityThe multistaged-hyperparallel method is implemented as a plugin in the JFuzzyMachine tool, freely available at the GitHub repository locations https://github.com/paiyetan/jfuzzymachine and https://github.com/paiyetan/jfuzzymachine/releases/tag/v1.7.21. Source codes and binaries are freely available at the specified URLs. Contactpaiyetan@gmu.edu
Magnetic and Structural Properties of Y6Mn2 3D2 3

The addition of hydrogen (deuterium) to compounds of the type R6Mn2 3 often has a dramatic effect on the magnetic properties of these compounds. For example, it has been reported (1) that Th6Mn2 3 is a Pauli paramagnet whereas Th6Mn2 3H2 3 is ferromagnetic with Tc = 355°K. By contrast, Y6Mn2 3 is ferrimagnetic (2) while Y6Mn2 3D2 3 shows no net spontaneous magnetization, even at 4.2 °K (1). In an attempt to explain the effect of the addition of deuterium, this study is aimed at ascertaining the crystallographic deuterium positions and the magnetic structure for Y6Mn2 3D2 3. Powder neutron diffraction data show no evidence of magnetic ordering at 298°K, but do show evidence of antiferromagnetism at 80°K. A modified Rietveld profile technique along with magnetic susceptibility measurements have been used to confirm this.
Extracting and Interpreting the Effects of Higher Order Sequence Features on Peptide MHC Binding

Understanding the factors contributing to peptide MHC (pMHC) affinity is critical for the study of immune responses and the development of novel therapeutics. Developments in yeast display platforms have enabled the collection of pMHC binding data for vast libraries of peptides. However, methods for interpreting this data are still at an early stage. In this work we propose an approach for extracting peptide sequence features that affect pMHC binding from such datasets. In the process we develop the theoretical framework for fitting and interpreting these features. We demonstrate that these features accurately capture the kinetics underlying pMHC binding, and can be used to predict pMHC binding well enough to rival the current state of the art. We then analyze the extracted factors and show that they correlate with our current structural understanding of MHC molecules. Finally, we discuss the implication these factors have on the complexity of peptide engineering.
Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy.

The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naive T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function. SIGNIFICANCE: To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy.This article is highlighted in the In This Issue feature, p. 2113.
Extending the Shared Socioeconomic Pathways for sub-national impacts, adaptation, and vulnerability studies

Abstract The exploration of alternative socioeconomic futures is an important aspect of understanding the potential consequences of climate change. While socioeconomic scenarios are common and, at times essential, tools for the impacts, adaptation and vulnerability and integrated assessment modeling research communities, their approaches to scenario development have historically been quite distinct. However, increasing convergence of impacts, adaptation and vulnerability and integrated assessment modeling research in terms of scales of analysis suggests there may be value in the development of a common framework for socioeconomic scenarios. The Shared Socioeconomic Pathways represents an opportunity for the development of such a common framework. However, the scales at which these global storylines have been developed are largely incommensurate with the sub-national scales at which impacts, adaptation and vulnerability and, increasingly, integrated assessment modeling studies are conducted. The objective of this study was to develop sub-national and sectoral extensions of the global SSP storylines in order to identify future socioeconomic challenges for adaptation for the U.S. Southeast. A set of nested qualitative socioeconomic storyline elements, integrated storylines, and accompanying quantitative indicators were developed through an application of the Factor–Actor–Sector framework. In addition to revealing challenges and opportunities associated with the use of the SSPs as a basis for more refined scenario development, this study generated sub-national storyline elements and storylines that can subsequently be used to explore the implications of alternative sub-national socioeconomic futures for the assessment of climate change impacts and adaptation.
Simulating the Effects of Cross-Generational Cultural Transmission on Language Change

Language evolves in a socio-cultural environment. Apart from biological evolution and individual learning, cultural transmission also casts important influence on many aspects of language evolution. In this paper, based on the lexicon-syntax coevolution model, we extend the acquisition framework in our previous work to examine the roles of three forms of cultural transmission spanning the offspring, parent, and grandparent generations in language change. These transmissions are: those between the parent and offspring generations (PO), those within the offspring generation (OO), and those between the grandparent and offspring generations (GO). The simulation results of the considered model and relevant analyses illustrate not only the necessity of PO and OO transmissions for language change, thus echoing our previous findings, but also the importance of GO transmission, a form of cross-generational cultural transmission, on preserving the mutual understandability of the communal language across generations of individuals.
CAR-like membrane protein negatively regulates the intestinal barrier and promotes neutrophil transepithelial migration (60.6)

CAR-Like Membrane Protein (CLMP) is expressed in the intestinal epithelium and has been shown to be essential for embryonic intestinal development in Humans and Zebrafish; however, the role of CLMP...
Small sized MFCG for driving a high impedance load

End-initiated small volume magnetic flux compression generators (MFCG) have at least one order of magnitude higher energy density (by weight or volume) than capacitive energy storage with similar discharge time characteristics. Since the prime energy is built into the MFCG in form of HE, the capacitor looses even more ground if the necessary prime energy source and the charging supply are included in the weight/volume balance. However, simple MFCGs with a single helix produce high output energy only into low inductance loads, thus producing several 100 kA of current at a voltage level of only a few 10 kV. Many pulsed power devices require less current but a considerably higher voltage level. Two approaches for achieving a higher output voltage level, both utilizing two staged MFCGs, have been reported in the open literature. The first employs a more traditional transformer coupling; the second relies on a dynamic transformer or flux-trapping scheme. Although the traditional transformer coupling has theoretically the better efficiency, we chose the latter approach for our generator design, mostly since it requires a smaller number of components. Our generator has a total length of 250 mm, a helix inner diameter of 51 mm, and is wound with Teflon insulated stranded wire of different sizes in the range from AWG 12 to AWG 22. We have presently achieved an energy gain of /spl sim/ 8 and will discuss the generator performance based on experimental current/voltage waveforms.
Physical processes in the growth of the continental crust

Major mechanisms of crustal addition are volcanism and plutonism at plate boundaries and within plate interiors. One approach to deciding if island arc magmatism dominated ancient crustal growth is to assess the rate at which the process has operated in the recent past. The localized addition rates were found to be comparable to present day global rates. One physical observable that was used to constrain models of crustal growth is sea level. A simple physical model was developed to explore the consequences of constant freeboard (the height of the continents above sea level). Global geoid and sea floor topography data were used to identify and study oceanic plateaus and swells that have either continental crustal roots or anomalously thick ocean crusts.
The Rand Health Insurance Experiment for Children

Results of the Rand Health Insurance Experiment (the largest controlled trial of the impact of different amounts of copayment for child health services ever conducted) published in this issue of Pediatrics1 are a cause for concern among pediatricians. Two questions are posed by these studies. First, is the use of child health services price dependent or, in other words, do children use less health care if there is more out-of-pocket cost? The answer is yes, but mainly for office visits, not hospitalizations, for older children. This finding does not surprise most pediatricians. Most goods and services in our society are sensitive to price.
Monsignor Georges Lemaitre

Georges Henri Joseph Edouard Lemaitre was born at Charleroi in Belgium on 17 July 1894, the first child of Joseph Lemaitre and Marguerite Lannoy.
ICU EEG monitoring for vasospasm and other focal cortical disorders

Publisher Summary This chapter explores that recent technological developments have made digital, continuous EEG monitoring (cEEG) widely available. It reviews that this technique is increasingly used to detect the focal brain abnormalities, such as delayed cerebral ischemia (DCI) from vasospasm, recurrent or progressive ischemia in the stroke patient, and any other acute brain event. Digital EEG data can be transformed into power spectra by fast Fourier transformation (FFT), creating a large number of possible quantitative EEG (qEEG) parameters. These can be displayed as numbers or graphically as compressed spectral arrays (CSAs), histograms, or staggered arrays. The chapter also discusses that some studies suggest that intracranial recording of cortical spreading depression (CSD) and periinfarct depolarizations may also be a powerful tool in monitoring the injured brain and preventing secondary injury. Ideally these techniques are integrated into multimodalbrain monitoring of the severely brain-injured patient, also including blood pressure, oxygen saturation, temperature, cerebral perfusion pressure (CPP), intracranial pressure (ICP), microdialysis, transcranial doppler (TCD) sonography, and brain tissue oxygen tension.
The Future of Nanoelectronics: New Materials, Architectures and Devices

This presentation describes the challenges and recent progress toward the most prominent candidates for becoming the next nanoelectronic switch where new materials, architectures and devices are crucial.
Rational Control of Enzymatic Enantioselectivity through Solvation Thermodynamics

The enantioselectivity of cross-linked crystals of γ-chymotrypsin in the transesterification of the medicinally important compound methyl 3-hydroxy-2-phenylpropionate (1) with propanol has been examined in a variety of organic solvents. The (kcat/KM)S/kcat/KM)R ratio in this enzymatic process can be forced to span a 20-fold range simply by switching from one solvent to another; in fact, while the enzyme strongly prefers the S-enantiomer of 1 in some solvents, the R-antipode is more reactive in others. These striking observations are quantitatively rationalized by accounting for the energetics of desolvation of S-1 and R-1 in the enzyme-bound transition states. In order to accomplish this, explicit rules have been established for the modeling and thermodynamic quantification of the partially desolvated substrate's transition state moieties.
Anomalies in Infrared Transmission Spectra Caused by the Self-Emission of Translucent Samples

The use of infrared-absorption techniques has become increasingly more prevalent and, with continued improvements in instrumentation, it has become possible to examine a wide variety of materials by transmission–absorption methods. Double-beam operation, increased detector sensitivity, scale expansion, and other instrumental improvements leading to high sensitivity and signal-to-noise ratios also lead to the spectral study of samples of very low transmittance, making such studies feasible if not facile. We have made such measurements with a variety of samples having transmittances below about 1%, using Perkin-Elmer model 521 and model 621 spectrophotometers, and have found that the apparent transmittance of a sample may be anomalously high if the sample is optically thick. The anomaly is caused by the emission of the sample. Similar emission effects have been mentioned, but seem to be generally disregarded. Typical effects are shown by the transmission spectra in Fig. 1, paper samples being used as examples because of the case of changing the sample thickness.
Chronic Stress Enhances Methamphetamine-Induced Extracellular Glutamate and Excitotoxicity in the Rat Striatum

Striking parallels exist between the neurochemical and toxic effects of stress and methamphetamine. Despite these similarities, no studies have examined how stress may promote the toxic effects of methamphetamine (METH). The current study tested the hypothesis that chronic stress enhances METH toxicity by augmenting glutamate (GLU) release and excitotoxicity in response to METH administration. Adult male Sprague-Dawley rats were exposed to 10 days of unpredictable stress and then received either saline or METH (7.5 mg/kg, i.p., once every 2 h × four injections). Prior exposure to unpredictable stress acutely enhanced the striatal extracellular GLU concentrations in response to METH, and eventually caused proteolysis of the cytoskeleton protein spectrin. Administration of the corticosterone synthesis inhibitor, metyrapone (25 mg/kg, i.p., prior to each stressor), during unpredictable stress attenuated the enhanced striatal GLU release in response to METH, blocked spectrin proteolysis, and attenuated METH-associated toxicity measured by long-term depletions in the dopamine and serotonin tissue content as well as depletions in dopamine and serotonin transporter immunoreactivity of the striatum. In summary, prior exposure to unpredictable stress enhances METH-induced elevations of GLU in the striatum, resulting in long-term excitotoxic damage and an augmentation of damage to dopamine and serotonin terminals. These studies provide a neurochemical basis for how stress contributes to the deleterious effects of METH abuse.
Traumatic brain injury and the goals of care. The ordeal of reminding.

The appropriate goal of care for a person with a traumatic brain injury is rehabilitation in the broad, etymological sense of the word. The task is to bring the person back to the conditions of the living of a life. This requires the rehabilitation of the mind—the reconstruction of a subject.
The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist.

The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A2A adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extended conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.
Treatment responsiveness of the Singing Voice Handicap Index.

Objectives/Hypothesis: To examine the responsiveness of the previously validated Singing Voice Handicap Index (SVHI) to treatment related changes in patients' singing voice. Study Design: Prospective. Methods: Thirty singing patients at a tertiary voice clinic prospectively completed the Voice Handicap Index and SVHI at their initial presentation, pretreatment, and posttreatment. Results: Patients had lower SVHI scores posttherapy compared with the initial SVHI scores (P ≤ .001, paired t-test). The change in SVHI scores from initial to posttreatment evaluation was greater than the change from initial to pretreatment evaluation (P < .001, paired t-test). The Spearman correlation of the Voice Handicap Index difference with the SVHI difference before and after treatment was 0.71 (P < .001). Conclusion: The SVHI measures changes in patients' singing vocal health status resulting from treatment and the change correlates with that of other validated instruments.
The biot drag and virtual mass coefficients for face centered cubic granular materials

Abstract The Biot equations model the propagation of acoustic waves in fluid-saturated porous media. The “drag” and “virtual mass” coefficients in the equations depend on the physical properties of the fluid and solid constituents, the frequency and the microstructure of the porous medium. Recently, a method has been developed for determining the drag and virtual mass coefficients as functions of frequency. The method requires solving for the motion of the fluid in the pores when the pore walls are subjected to a spatially uniform, oscillatory motion. In this work we use the finite element method to compute the fluid motion and evaluate the drag and virtual mass coefficients for granular media consisting of spherical and polyhedral grains with face centered cubic (fcc) packings. The materials we consider have porosities that range from 0.261 to 0.480. We conclude that an empirical approach based on Biot's results for cylindrical pores can adequately approximate our computations for an fcc packing of spheres.
Tratamiento de una fístula de arteria mesentérica superior y vena porta con endoprótesis expandible por balón

Las fistulas arteriovenosas de arteria visceral a vena porta son raras y dificiles de tratar. Los stents cubiertos han hecho viable el tratamiento de los pseudoaneurismas y fistulas arteriovenosas con el uso de tecnicas minimamente cruentas. Presentamos un caso clinico de un hombre de 46 anos de edad con antecedentes de laparotomia exploradora, realizada muchos anos atras despues de un accidente de trafico con ciclomotor, que se presento con dolor abdominal, malestar e ictericia. La tomografia computarizada revelo una fistula arteriovenosa de arteria mesenterica superior a vena porta. La arteriografia confirmo su gran tamano. Se implanto un stent expandible montado sobre un balon a traves de la fistula en la arteria mesenterica superior. Despues del procedimiento, el dolor abdominal remitio y su concentracion de bilirrubina disminuyo desde 2,9 a 0,4. La reparacion endovascular de la fistula arteriovenosa de arteria mesenterica superior a vena porta mediante una endoprotesis es viable y minimamente cruenta.
47.3: Color Separation 3D in a Laser Projection System Using a 2D MEMS Scanner

This experiment created a mobile 2D/3D switchable laser projection system which uses a 2D MEMS scanner. This system can display a two-dimensional (2D) or a three-dimensional (3D) image in only one optical engine. In particular, we propose the use of a mobile Color Separation 3D laser projection system that uses different wavelengths of laser diodes. This projection system can display the left and right stereoscopic images simultaneously in one optical engine without using other components such as an alternate color wheel. In this study, the 0.35% and 0.53% crosstalk for left and right has been achieved by separating the wavelengths using filter glasses in a laser projection system consisting of a 2D MEMS scanner and two sets of Red, Green and Blue laser diodes.
Influence of Structural Fluctuation on Enzyme Reaction Energy Barriers in Combined Quantum Mechanical/Molecular Mechanical Studies

To account for protein dynamics and to investigate the effect of different conformations on the enzyme reaction energy barrier, we have studied the initial step of the acylation reaction catalyzed by acetylcholinesterase (AChE) with a multiple QM/MM reaction path approach. The approach consists of two main components: generating enzyme−substrate conformations with classical molecular dynamics simulation and mapping out the minimum reaction energy path for each conformational snapshot with combined quantum mechanical/molecular mechanical (QM/MM) calculations. It is found that enzyme−substrate conformation fluctuations lead to significant differences in the calculated reaction energy barrier; however, the qualitative picture of the role of the catalytic triad and oxyanion hole in AChE catalysis is very consistent. Our results emphasize the importance of employing multiple starting structures in the QM/MM study of enzyme reactions and indicate that structural fluctuation is an integral part of the enzyme re...
Preparation of halo--methanes potassium fluoride-halogen cleavage of halo--methylphosphonium salts

Abstract Treatment of halo- F -methylphosphonium salts with potassium fluoride and halogen (I2, Br2, ICl, IBr) gives modest yields of halo- F -methanes. This method of preparation augments the classical Hunsdiecker approach to these materials.
Cognitive competition and hypnotic behavior: whither absorption?

Abstract According to the widely held absorption notion, the successful response to hypnotic suggestions requires S to focus attention on the content of these suggestions and to avoid incompatible and contradictory cognitive activities. This assumption was tested by exposing high, middle, and low hypnotizable Ss continuously to incompatible suggestions and images as they attempted to respond to the direct suggestions of the hypnotist. Performance under these circumstances was substantially as effective as in baseline sessions (without incompatible suggestions) for the high and medium hypnotizable Ss. On the other hand, fewer than half of the low hypnotizable Ss responded successfully. The results are viewed as compatible with both a social enactment and a neodissociation interpretation of hypnosis.
Glucosamine-induced phosphorylation of the α-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinase

In diabetic animals, enhanced production of vascular endothelial growth factor is thought to be a major contributor to the development of diabetic retinopathy. In the present study, glucosamine-treated R28 retinal neuronal cells were used as an experimental model system to explore the possible involvement of the hexosamine biosynthetic pathway in the diabetes-induced changes in mRNA translation. Glucosamine treatment enhanced vascular endothelial growth factor production subsequent to changes in phosphorylation of the alpha-subunit of eukaryotic initiation factor 2, with no change in vascular endothelial growth factor mRNA content. Possible mechanisms through which glucosamine might act to increase eukaryotic initiation factor 2alpha phosphorylation include enhanced O-linked glycosylation of protein kinase or phosphatase regulatory proteins and/or induction of oxidative stress. However, increasing global protein O-glycosylation through inhibition of O-beta-N-acetylglucosaminidase did not mimic the effect of glucosamine on eukaryotic initiation factor 2alpha phosphorylation. Likewise, attenuating glucosamine-induced oxidative stress with two different antioxidants did not reduce glucosamine-induced eukaryotic initiation factor 2alpha phosphorylation. Glucosamine treatment was also found to promote eukaryotic initiation factor 2alpha phosphorylation in wild-type mouse embryonic fibroblasts, but not in mouse embryonic fibroblasts lacking the eukaryotic initiation factor 2alpha kinase referred to as RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, implicating the kinase in the glucosamine-induced increase in eukaryotic initiation factor 2alpha phosphorylation. Overall, the results are consistent with glucosamine causing activation of RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, which phosphorylates eukaryotic initiation factor 2alpha and consequently upregulates translation of mRNAs encoding specific proteins, such as vascular endothelial growth factor.
Reaction time as a predictor of imaginative suggestibility and hypnotizability.

The purpose of this exploratory investigation was to examine the relationship between reaction time, hypnotizability and imaginative suggestibility. The study participants were 119 undergraduate students who were assessed for non-hypnotic and hypnotic suggestibility, performed simple and go/no-go reaction time tasks and completed response expectancy, motivation, absorption and fantasy-proneness scales. Faster simple response times were associated with greater hypnotic suggestibility, hypnotizability, response expectancies, absorption, fantasy-proneness and non-hypnotic motivation. Go/no-go response time was not significantly correlated with any of these measures. With the other controlled, each reaction time measure was uniquely associated with hypnotic expectancy, hypnotic suggestibility, and hypnotizability, but in opposite directions. Copyright © 2001 British Society of Experimental and Clinical Hypnosis
Cricopharyngeal myotomy and arytenoid adduction in the management of combined laryngeal and pharyngeal paralysis

Aspiration caused by unilateral combined laryngeal and pharyngeal paralysis is a serious clinical problem. This article reviews the abnormal physiology, which includes glottal incompetence, impaired pharyngeal propulsion, and sensory loss, and reports the results of surgical treatment of, 13 patients who had significant dysphagia and aspiration caused by unilateral laryngeal and pharyngeal paralysis. In eight patients the cause was surgical resection or trauma of the tenth cranial nerve, with concomitant twelfth nerve injury in four. Four patients had central lesions. One patient had a surgical tenth cranial nerve injury as well as a stroke. Thyroplasty, alone in two patients, and combined with cricopharyngeal myotomy in a third, improved voice, but not swallowing. In all patients treated by arytenoid adduction plus cricopharyngeal myotomy, aspiration was eliminated, and patients gained weight. Six of these patients had been dependent on enteral tube feedings. The results support the safety and efficacy of simultaneous arytenoid adduction and cricopharyngeal myotomy for dysphagia caused by combined laryngeal and pharyngeal paralysis.
Evaluation of search strategies and cost functions in optimizing voxel-based image registration

A number of image registration algorithms are currently used to register both intra-modality and inter-modality image data sets. These algorithms, although tested, have not always been optimized or evaluated in relationship to other registration algorithms available. Analysis of registration algorithms is often difficult, due to the fact that the registration components are integrated with each other and cannot be easily isolated form the rest of the algorithm. This study outlines some important features of registration algorithms and describes a method by which these algorithms may be analyzed. This method was used to analyze (1) two cost functions, a normalized standard deviation function and a conditional entropy function, (2) two search strategies, Powell's method and a derivative method, and (3) a number of iterative relaxation/data reduction techniques. These registration components were tested with a number of intra- modal and inter-modal data sets. The cost function analyses suggest that segmentation is necessary for some inter-modal registration problems. Multi-resolution techniques are also discussed with regard to registration effectiveness. A Euclidean distance measure was used to conditional entropy combined with a derivative search strategy may be the most robust approach to image registration, whereas the normalized standard deviation with Powell's search strategy produces the worst results. Generalization and further work are indicate in the discussion.
Light-induced transformations of a spironorcaradiene☆☆☆

Abstract Norcaradiene 2 undergoes two kinds of photochemical reaction. 4,4-Dimethylcyclohexadienylidene is extruded on irradiation through quartz, but not when 2 is shielded by Pyrex. The carbene can be trapped with various olefins and a comparison of the properties of the carbene formed from 2 and on photolysis of 4,4-dimethyldiazocyclohexadiene reveals them to be identical. In either quartz or Pyrex an isomer of 2 is formed which is thought to possess structure 3d. Heating of 3d at 100° produces still another isomer, 4a, which can be reconverted to 3d on irradiation. Structures for 3d and 4a are proposed and mechanisms for their formation suggested.
Water storage in the mantle

The origins of the oceans and Earth's volatile atmosphere are major unsolved problems in earth sciences. The recent study by Finger et al. of the crystal chemistry of a water-bearing mineral phase, cryptically named phase B and grown under conditions equivalent to a depth in the Earth of 360 km, dramatically demonstrates that several times the Earth's visible water budget could be stored in the mantle.
The preparation and evaluation of tangerine peel tincture and tangerine syrup.

A tangerine peel tincture was prepared by maceration of the whole peel from the fresh fruit. In the determination of the oil content of the tinctures, an adaption of the A. O. A. C. precipitation method appeared to have a greater general accuracy than the polarization method. A tangerine syrup was prepared from the tincture, using light magnesium carbonate as the filtering agent. Organoleptic tests indicated that tangerine syrup compared favorably in taste preference with five other vehicles which had ranked high in taste preference tests conducted by other workers. Tangerine syrup also appeared to have a high value in disguising the salty taste of ammonium chloride and a mediocre value in disguising the bitter taste of quinine hydrochloride.
The Student Pediatric Society: an intervention to promote a career in pediatrics.

A number of strategies have been proposed to stimulate medical student interest in 1 or all of the generalist or primary care disciplines. 1-2 Some studies suggest that a primary care–oriented curriculum may affect medical student career choice. 1-5 Based on the family medicine experience with student interest groups, we hypothesized that an extracurricular intervention would stimulate medical students to pursue a generalist career in pediatrics 4 (Robert Jones, DEd, written communication, December 6,1996). Medical student interest groups, or discipline specific "clubs," began at The Pennsylvania State University (PSU) College of Medicine, with the establishment of the Family Practice Interest Group, as early as 1973. In nearly all cases, student interest prompted the creation of such organizations. Currently, at least 7 such groups are active at PSU. In 1994, the American Academy of Pediatrics Committee on Careers and Opportunities conducted a survey of US and Canadian medical schools about organized
Effect of nembutal anesthesia upon purkinje cell activation in the cat

Abstract Cerebellar evoked phenomena were recorded from eighty-six cats, comparing successively field potential and Purkinje cell ( P cell) unit responses under local procaine block in the flaxedilized animal and Nembutal (30 mg/kg) anesthesia. The configurations and latencies of the field potentials which followed stimulation of folial surface and olivary and pontine afferent sources were not altered by the induction of Nembutal anesthesia, but unit P cell responses were changed significantly. Using extracellular micro-electrodes, a clearly discernible depletion in spontaneous unit activity occurs during the transition from locally anesthetized to nembutalized state. With this depletion a change in P cell unit response to stimulation occurs. Before Nembutal, surface folial stimulation may be followed by up to 14 unit spikes occuring during the negative phase of the surface-evoked potential, whereas after Nembutal, surface stimuli produce a maximum of but two such spikes. After Nembutal, as before, the pontine responses retain their single spike character, synchronous with the N 3 wave of the field potential, whereas that of the olivo-cerebellar response changes from a single unit spike in the pre-Nembutal record to the classical repetitive spike pattern of the nembutalized preparation designated “climbing fiber response” by Eccles (1966a). Superior laryngeal nerve field and unit potentials recorded from crus I and folia III and IV of the paramedian lobule under Nembutal resemble the corresponding olivocerebellar response.
Fluidized bed expansion as a result of biomass growth

A relationship which is capable of predicting the height of a fluidized bed with the extent of the biomass growth at the surface of the fluidized particles is proposed. The application of this relationship for the determination of one of the biological parameters of waste water treatment is demonstrated. On propose une relation qui permet de prevoir la variation de la hauteur d'un lit fluidise avec la croissance de la biomasse a la surface des particules fluidisees. On demontre l'application de cette relation a la determination de l'un des parametres biologiques du traitement des eaux residuaires.