cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure-guided drug design: Conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes

Neuronal nicotinic receptors, encoded by nine genes of the alpha and three of the beta type of subunits, and whose gene products assemble in distinct permutations as pentameric molecules, constitute a fertile area for structure-guided drug design. Design strategies are augmented by a wide variety of peptide, alkaloid and terpenoid toxins from various marine and terrestrial species that interact with nicotinic receptors. Also, acetylcholine-binding proteins from mollusks, as structural surrogates of the receptor that mimic its extracellular domain, provide atomic resolution templates for analysis of structure and response. Herein, we describe a structure-guided approach to nicotinic ligand design that employs crystallography of this protein as the basic template, but also takes into consideration the dynamic properties of the receptor molecules in their biological media. We present the crystallographic structures of several complexes of various agonists and antagonists that associate with the agonist site and can competitively block the action of acetylcholine. In so far as the extracellular domain is involved, we identify additional non-competitive sites at those subunit interfaces where agonists do not preferentially bind. Ligand association at these interface sites may modulate receptor function. Ligand binding is also shown by solution-based spectroscopic and spectrometric methods to affect the dynamics of discrete domains of the receptor molecule. The surrogate receptor molecules can then be employed to design ligands selective for receptor subtype through the novel methods of freeze-frame, click chemistry that uses the very structure of the target molecule as a template for synthesis of the inhibitor.
What causes childhood brain tumors? Limited knowledge, many clues.

Little is known about the causes of brain tumors in children. Children with one of several genetic disorders including tuberous sclerosis and Li-Fraumeni syndrome are at increased risk, as are children who have received therapeutic irradiation to their head. The multifactorial causation of brain tumors, the inaccuracies of recall of past exposures, and the study of all pediatric brain tumors as a single etiologic entity may be contributing to the difficulty in identifying additional risk factors. The evidence that frequent cured meat consumption by the mother during pregnancy increases the risk is suggestive but not conclusive. For other potential risk factors, the evidence is limited and/or conflicting. These exposures and characteristics include pesticides, carcinogen metabolizing genes, and polyomaviruses.
Effect of dead space on the excess noise factor and time response of avalanche photodiodes

The effect of dead space on the statistics of the gain process in continuous-multiplication avalanche photodiodes (APDs) is determined using the theory of age-dependent branching processes. The dead space is the minimum distance that a newly generated carrier must travel in order to acquire sufficient energy to cause an impact ionization. Analytical expressions are derived for the mean gain, the excess noise factor, and the mean and standard deviation of the impulse response function, for the dead-space-modified avalanche photodiode (DAPD), under conditions of single carrier multiplication. The results differ considerably from the well-known formulas derived by R.J. McIntyre and S.D. Personick in the absence of dead space. Relatively simple asymptotic expressions for the mean gain and excess noise factor are obtained for devices with long multiplication regions. In terms of the signal-to-noise ratio (SNR) of an optical receiver in the presence of circuit noise, it is established that there is a salutory effect of using a properly designed DAPD in place of a conventional APD. The relative merits of using DAPD versus a multilayer (superlattice) avalanche photodiode (SAPD) are examined in the context of receiver SNR; the best choice turns out to depend on which device parameters are used for the comparison. >
Limit laws for upper and lower extremes from stationary mixing sequences

The aim of this paper is to examine the weak limiting behavior of upper and lower extremes from stationary sequences satisfying dependence conditions similar to D and D′ introduced by Leadbetter (Z. Wahrsch. Verw. Gebiete 28 (1974), 289–303). By establishing the convergence in distribution of an associated sequence of point processes, the joint limiting distribution of any collection of upper and lower extremes can be determined. Sufficient and, in some cases, necessary conditions for the asymptotic independence of the upper and lower extremes are also given.
Synthesis and Stabilization of Silver Metallic Nanoparticles and Premetallic Intermediates in Perfluoropolyether/CO2 Reverse Micelle Systems

This article presents the stabilization of silver nanoparticle intermediates synthesized in ammonium perfluoropolyether (PFPE-NH4) reverse micelles with supercritical fluid (SCF) carbon dioxide sol...
Evaluation of a worker with possible formaldehyde-induced asthma

Abstract Background: We describe the evaluation of a worker with clinical symptoms compatible with bronchospasm caused by formaldehyde exposure. Methods: The worker was evaluated by means of enzyme-linked immunosorbent assay, cutaneous tests, and methacholine and formaldehyde inhalation challenges. The worker's serum was injected intradermally into the skin of a normal rhesus monkey to determine whether hypersensitivity could be transferred from human to primate. Results: An enzyme-linked immunosorbent assay showed that the worker had positive IgE and IgG titers to formaldehyde-human serum albumin. The worker had a positive cutaneous test for formaldehyde-human serum albumin, and this cutaneous reactivity was transferred to a rhesus monkey through the worker's serum. The worker had a negative methacholine challenge at 25 mg/ml and negative formaldehyde inhalation challenges at 0.3, 1, 3, and 5 ppm for 20 minutes. It is possible that the worker would have had a positive result if a higher concentration of F were used for the challenge, but it is more probable that the worker's symptoms were not caused by immunologically mediated asthma. We have studied individuals exposed to formaldehyde, their clinical syndromes, and serologic results for a decade. This worker is the one subject with the most compatible history and immunology, but the worker had a negative challenge. Conclusion: Immunologically mediated asthma caused by formaldehyde is extremely rare, if it exists at all.
Long-term follow-up of patients with cardiac pacemakers∗

Abstract One hundred and ninety patients have had implantation of intracorporeal electronic cardiac pacemakers at the Mount Sinai Hospital between September 1962 and May 1967. Transthoracic units were employed in 91 cases (mean follow-up interval 38.5 mo.), and transvenous pacers were used in 99 patients (mean interval 9.9 mo.). One hundred reoperations have been performed, 74 in the transthoracic group and 26 in the transvenous series. Analysis of failure rates at six months following surgery discloses 25 reoperations in 91 patients with transthoracic pacemakers (27%) and 17 reoperations in 64 with transvenous catheter pacemakers (27%). However, the magnitude of the operative procedures has been less in the latter group. There have been 35 deaths, 25 in the transthoracic series and 10 in the transvenous series, although 30-day mortality has been 5 and 3 per cent, respectively. Six month mortality is 15 per cent for the transthoracic pacemaker group and 8 per cent for the transvenous series. Most patients have died from diseases unassociated with their heart block. Comparison of mortality rates for patients with Stokes-Adams syndrome treated medically and surgically reveals that substantial improvement in prognosis has been achieved by the use of implantable electronic pacemakers.
Rapid determination of RNA accessible sites by surface plasmon resonance detection of hybridization to DNA arrays.

RNA accessible sites are the regions in an RNA molecule that are available for hybridization with cDNA or RNA molecules. The identification of these accessible sites is a critical first step in identifying antisense-mediated gene suppression sites, as well as in a variety of other RNA-based analysis methods. Here, we present a rapid, hybridization-based, label-free method of identifying RNA accessible sites with surface plasmon resonance imaging (SPRi) on in situ synthesized oligonucleotide arrays prepared on carbon-on-metal substrates. The accessible sites of three pre-miRNAs, miRNA precursors of ∼75 nt in length, were determined by hybridizing the RNA molecules to RNA-specific tiling arrays. An array composed of all possible 6mer oligonucleotide sequences was also utilized in this work, offering a universal platform capable of studying RNA molecules in a high throughput manner.
Fine Structure of Plasmodium gallinaceum in Embryonic and Neonate Chicks

SYNOPSIS. The erythrocytic stages of Plasmodium gallinaceum in chicken embryos injected with parasitized blood either from a syringe-passaged infection in chickens or from a chicken infected with sporozoites, were characterized by abnormal structure. Particularly evident were large, unstained vacuoles within the cytoplasm; these occurred with greatest frequency in schizonts. The presence of myelin bodies within these vacuoles was revealed by transmission electron microscopy; abnormal cytokinesis and aberrant merozoites provided additional evidence of the parasite's inability to develop naturally within the milieu of the embryonic erythrocytes. Fifty-five passages were necessary to restore normal structure of the parasites in embryos, while only 5 passages were required for such restoration in neonate chicks. The probable adaptation of the parasite to the proportions of hemoglobin of the adult chicken may be responsible for the abnormal growth in the immature host.
A comparison of routine and rapid microwave tissue processing in a surgical pathology laboratory. Quality of histologic sections and advantages of microwave processing.

Rapid processing of histopathologic material is becoming increasingly desirable to fulfill the needs of clinicians treating acutely ill patients. Traditional techniques for rapid processing of paraffin-embedded tissues require 4 to 5 hours, delaying treatment for some critically ill patients and requiring additional shifts of technologists in the laboratory. Microwave processing further shortens this time, allowing even more rapid histopathologic diagnosis. Few data exist comparing quality of microwave-processed tissue with that processed by more traditional techniques. We randomly selected 158 paired specimens from 111 patients. One member of the pair was processed routinely overnight, while the other was processed by the rapid microwave technique. The slides then were compared for quality of histologic preparation in a blinded fashion by 2 pathologists. Eight routinely processed specimens were judged as suboptimal, while 6 microwave-processed specimens were judged as suboptimal and 1 was considered unsatisfactory for evaluation. In the remaining cases, the material obtained by the 2 techniques was considered of identical quality. Microwave processing considerably shortens the preparation time for permanent histologic sections without a demonstrable decrease in section quality or "readability."
The vibrational frequencies of borane (BH3) : a comparison of high level theoretical results

Abstract Using the borane molecule, BH 3 , as an example, a detailed comparison is made among the results achieved using many levels of theory for the treatment of electron correlation. In particular, with three different basis sets ranging from a simple double-ζ plus polarization (DZP) to the very flexible triple-ζ plus two sets of polarization functions plus higher angular momentum functions (TZ2P(f,d)), total energetic, geometrical and harmonic vibrational frequency results from several of the more complete single reference methods of electron correlation are compared to the full configuration interaction (FCI) results. Emphasis is placed on comparison of augmented coupled cluster (CCSD(T)) theory and the CI method including all singles, doubles, triples and quadruples (CISDTQ) methods with FCI. These high-level results may also provide some additional insight into the ongoing controversy surrounding the experimentally assigned fundamental vibrational frequencies of BH 3 . The TZ2P(f,d) CCSD(T) harmonic vibrational frequencies predicted in this work were ω 1 = 2567, ω 2 = 1163, ω 3 = 2696 and ω 4 = 1223 cm −1 implying experimental misassignments by Kaldor and Porter [J.Am.Chem.Soc.,93 (1971) 2140] of the third and fourth vibrational frequencies, in agreement with previous theoretical works.
Preface: Biology of skates

Skates have become a concern in recent years due to the preponderance of these elasmobranchs that are caught as bycatch or as a directed fishery. This has raised concern because skates have life history characteristics that may make them vulnerable to over-exploitation. It was due to this increasing awareness and concern about these batoids that prompted us to organize an international symposium on the “Biology of Skates”. The aims and goals of the symposium were to bring together an international group of researchers to meet, discuss, perhaps develop collaborations, and present their most recent findings. The symposium was held over two days, on 13–14 July, 2006, in conjunction with the 22nd annual meeting of the American Elasmobranch Society in New Orleans, LA. A total of 31 authors from four countries contributed 16 papers that appear in this special issue. The papers are broadly arranged into four separate categories: systematics and biogeography, diet and feeding ecology, reproductive biology, and age and growth. To the best of our knowledge this is the first dedicated book on the biology of skates. We hope that readers will find this issue of interest and that it helps encourage and stimulate future research into these fascinating fishes.
Processing and packaging automation systems: a review

Global food processing and packaging business has reached to multi trillion dollars as the consumers have started using processed food more than the staples. This paper reviews aspects of systems, standards and interfaces for the modern food industry. It presents processing and packaging principles, methods, techniques, standards, interfaces, and state-of-the-art technology. The primary purpose of this paper is to update the information in this domain so that not only the novice practitioner will gain much out of this review but the system integrators, researchers, and the stakeholders as well. In addition, the paper covers recent advances in smart packaging materials, the examples of nanotechnology in packaging, material handling systems, application of robotics, non-destructive inspection methods, packaging execution systems (PES), distributed control and automation systems, traceability, and finally OMAC (Open Modular Architecture Controls) guidelines on software standards and interfaces.
Selected Bibliography of Health-Related Mistrust among Minority Populations

Abstract The following bibliography was compiled from searches of AIDSline, BioethicsLine, Medline, PsycLfT, and Sociofile databases. It is not exhaustive of every reference of mistrust in the health sciences literature, but remains fairly comprehensive in its scope. References were compiled by searching for: (1) articles that mentioned “distrust or mistrust,” (2) articles on “physician-patient relations” and “attitude of health personnel,” and (3) cross referencing material from the first two searches with each minority category. The term “minority” in the bibliography is used broadly to encompass ethnicity, race, sex, and sexual orientation. Each ethnic, racial, sex, or sexual orientation category is further broken down into sub-categories of related topics. For instance, a subcategory of “provider attitudes” toward specific groups is included throughout the bibliography because attitudes and actions of health care providers can help shape and fuel community mistrust. The authors recognize that the chos...
Multiple sulfatase deficiency

Multiple sulfatase deficiency is an inherited disorder characterized by a deficiency of several sulfatases and the accumulation of sulfatides, glycosaminoglycans, sphingolipids, and steroid sulfates in tissues and body fluids. The clinical manifestations represent the summation of two diseases: late infantile metachromatic leukodystrophy and mucopolysaccharidosis. We present a 9-year-old girl with a phenotype similar to a mucopolysaccharidosis: short stature, microcephaly, and mild facial dysmorphism, along with dysphagia, retinal degeneration, developmental arrest, and ataxia. We discuss the importance of measuring the sulfatase activities in the leukocytes, and the instability of sulfatases in the cultured skin fibroblasts.
Quark spin properties at high x

Abstract A general three quark bound state satisfying the Pauli principle, and conserving angular momentum and isospin, is used to investigate the spin structure of nucleons at high x . It is shown if F 1 n / F 1 p →1/4, then both A 1 p and A 1 n , as well as quark spin distribution Δ u / u , will approach 1 as x →1 in polarized deep inelastic scattering. The spin distribution Δ d / d does not approach 1, but is bound by the limits −1/3⩽Δ d / d ⩽0 for any x .
Spectral downwelling irradiance in an Antarctic lake

Spectral downwelling irradiance (400–700 nm) was determined in the ice-covered Lake Hoare located in the dry valleys near McMurdo Sound, Antarctica. Full waveband PAR beneath the ice was <44μE·m-2·s-1 or <3% of surface downwelling irradiance. Maximum light transmission just beneath the 2.6–4 m ice cover, which contained sediments and air bubbles, occurred between 400–500 nm. In the water column below, attenuation of light by phytoplankton in the 400–500 nm region and between 656–671 nm suggested absorption of light by algal pigments.
Ultraviolet photodesorption as a driver of water migration on the lunar surface

Abstract We have studied the photodesorption of monolayer coverage of water ice coating amorphous carbon by 193 nm photons. We found that the column density of water decreases exponentially with fluence during irradiation at 120 K and obtain a desorption cross-section of (7.4±0.5)×10–19 cm2. We estimate the lifetime for photodesorption to be ∼14 h for average solar activity at the sub-solar point on the Moon. The photodesorbed molecules, based on other experiments, are expected to be slower than the escape velocity and to be re-adsorbed on the surface, contributing to water migration. For comparison, we determine the effect of 4 keV He+ on water-coated Apollo 16 soil (65901) under similar experimental conditions. We find a sputtering cross-section of (1.2 ±0.4)×10–16 cm2. We calculate that photodesorption by solar UV is four orders of magnitude more effective than sputtering by the solar wind in causing migration of adsorbed water on the lunar surface.
Timed inhibition of p38MAPK directs accelerated differentiation of human embryonic stem cells into cardiomyocytes

Background aims Heart failure therapy with human embryonic stem cell (hESC)-derived cardiomyocytes (hCM) has been limited by the low rate of spontaneous hCM differentiation. As others have shown that p38 mitogen-activated protein kinase (p38MAPK) directs neurogenesis from mouse embryonic stem cells, we investigated whether the p38MAPK inhibitor, SB203580, might influence hCM differentiation.
The gi/m/1 processor-sharing queue and its heavy traffic analysis

In this paper, we find the Laplace-Stieltjes transform of the customer stationary distribution of time spent in the system for the GI/M/1 queue with processor-sharing discipline. This distribution is characterized in three ways. The first is a method of successive approximations, the second is an integral representation and the third is a power series representation. Finally, we find a simple form for the heavy traffic limit (as the utilization gets close to 1) for the distribution of time spent in the system, suitably scaled.
Abstract C107: Isolation and characterization of human breast epithelial cells.

Breast cancer is one of the most common cancers among women in the United States and it is the second leading cause of cancer deaths in this population. Roughly 232,000 women in the U.S. were diagnosed with malignant breast cancer in 2013 and approximately 40,000 of these patients will die. The majority of breast cancers originate in the lobular or ductal cells of the milk-producing glands. In these structures, there are two main cell types: the inner luminal cells, which are surrounded by basal myoepithelium. These cells are structurally distinct and are the precursors to variable forms of breast cancer. As such, it is important to study them not only separately but also together. Current methods for culturing human mammary epithelial cells select for those of a basal phenotype. Isolation of pure basal and luminal cell populations was accomplished by using antibody-linked magnetic beads to isolate essentially pure populations of both basal (CALLA/CD10) and luminal mammary (MUC1/CD227) epithelial cells from organoid explant cultures. Organoids were isolated and plated on collagen I coated flasks in either DFCI (basal) or MBCM (luminal) media and cultured at 37°C in 5% CO2 to induce cell migration. The media was replenished every 2 - 3 days until the cells reached confluence. Cultured cells were harvested and immunopurified using a CALLA/CD10 or MUC1/CD227 antibody and magnetic beads. Positively selected cells were seeded in tissue culture treated flasks and propagated with medium exchange every 2 - 3 days. Each cell population was analyzed using flow cytometry to determine their purity. The DFCI/CD10 cells were over 98% CD10 positive with very little MUC1 reactivity, suggesting that they are an essentially pure basal epithelial cell population. The cells isolated using MBCM/MUC1 appear to be a mixed population with 86% MUC1 positive luminal cells and the remainder being CD10 positive basal cells. A second round of immunopurification resulted in an isolated cell population that was greater than 95% MUC1 positive, suggesting a pure luminal epithelial cell population. This procedure has been used on several organoid preparations and has generated high cell yields in addition to high cell purity. These isolated cell types can now be tested individually for drug sensitivity. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C107. Citation Format: Steven Hoynowski. Isolation and characterization of human breast epithelial cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C107.
A Proposed lunar orbiting gravity gradiometer experiment

Analysis of the gravity gradiometer developed by R. L. Forward and C. C. Bell at the Hughes Research Laboratories suggest than an accuracy, in the range 0.1 to 0.5 EU can be expected in a lunar orbiter application. This accuracy will allow gradient anomalies associated with mascons to be mapped with 1% accuracy and should reveal a great deal of new information about the lunar gravity field.
The “Whig Historian” on Adam Smith: Paul Samuelson's Canonical Classical Model

Facts, the historian E.H. Carr argued, are like fish in a vast ocean: what one catches to a large extent depends on where one chooses to fish and on the kind of tackle one uses. Professor Paul Samuelson has offered (HES Bulletin, Fall 1987) a prescription for stimulating demand for history of economics. He proposes “that history of economics more purposefully reorient itself toward studying the past from the standpoint of the present state of economic science. To use a pejorative term unpejoratively, I am suggesting Whig Economic History of Economic Analysis.” (Samuelson 1987: 52) Samuelson promises that fishing with the tackle of present-day theory will catch commercially attractive historical fish and illustrates this approach with his own work in history of economics.
The chemical significance of the tertiary structures of polypeptides and proteins

Abstract A molecular modeling review of the X-ray crystallographically determined structures of some proteins and polypeptides, from the Brookhaven Protein Data Bank, has enabled us to identify chemically reactive, weak, amidic linkages in some of these molecules. This discovery should add new dimensions to the discussion of the significance of the tertiary structures of proteins and polypeptides, and to the chemistry of these polymers.
An analysis on the exchange of indicators in single capillaries

Abstract A theoretical model is proposed to calculate the transcapillary exchange for the double-indicator dilution method. Laplace transform is used to derive the solution. It is shown that the exchange is governed by three dimensionless parameters: 2kl|va, D|ka, Dtm|a2 where k is the permeability of the wall of the capillary, l its length a its radius, v the average velocity, D the diffusion constant of the extravascular space, and tm the characteristic time of the time-concentration curve. The first parameter specifies the initial rate of the permeable substance passing across the capillary wall. The last two specify the diffusion into the extravascular space with respect to the permeation across the membrane. For D ka , the concentration buildup near the extravascular side of the capillary wall is shown to reduce significantly the exchange. For a smaller Dt m a 2 the buildup in the extravascular space is shown to be slower. Such results will be useful to the systematic studies of exchange in a capillary network.
Background on health effects of acid aerosols.

This introduction to the 1987 NIEHS-EPA Symposium on the Health Effects of Acid Aerosols reviews the state of our knowledge on this topic as of the close of the 1984 NIEHS Conference on the Health Effects of Acid Precipitation (Environmental Health Perspectives, Volume 63) and the results of some key studies completed since that time. These studies, together with the results of the studies presented in the papers that follow, provide a substantial increment in our knowledge of the health effects of acid aerosols.
Replication of the herpes simplex virus genome: does it really go around in circles?

Herpes simplex virus type 1 (HSV-1) is the prototype and best-studied virus of the α-herpesvirus group. HSV-1 undergoes a rapid productive replication cycle in host epithelial cells in vivo and in susceptible cultured cells in vitro . However, HSV-1 is also neurotropic and establishes life-long latent infections in the sensory neurons of the host, where the genome is in a nonreplicating chromatin-associated state (1), and viral gene expression is largely repressed (2). Although the mechanisms for the establishment of latency are poorly understood, reactivation requires an immediate early protein, termed ICP0, which is also required for efficient initiation of lytic infection (3–7). The 152-kb linear double-stranded HSV-1 genome is divided into long and short regions of unique sequences, termed UL and US, which are bounded by regions of inverted repeats, termed internal repeats. The genome termini are bounded by regions of direct repeats, termed terminal repeats (Fig. 1). Furthermore, the HSV-1 genome undergoes inversions that result from recombination events mediated by the viral DNA replication machinery, which yield four genomic isomers in equimolar amounts (8, 9). In vivo , the HSV-1 genome has been found to exist in at least three different states: linear, circular, and concatemeric. In the virion, genomes are linear, but within hours after infection, end joining has been found to occur, resulting in ``endless genomes'' that have been interpreted to represent circles (10–12). Although the mechanism of genome circularization has not been established, one model predicts that circularization may involve recombination of the terminal repeats, resulting in a θ replication mode for the initial round of replication (13), providing the template for a rolling circle mode of replication (14). Thus, genome circularization has been thought to be a prerequisite for viral DNA replication, although …
Nonlocal evolutions for image regularization

A nonlocal quadratic functional of weighted differences is examined. The weights are based on image features and represent the affinity between different pixels in the image. By prescribing different formulas for the weights, one can generalize many local and nonlocal linear denoising algorithms, including nonlocal means and bilateral filters. The steepest descent for minimizing the functional can be interpreted as a nonlocal diffusion process. We show state of the art denoising results using the nonlocal flow.
Intramolecular van der waals interactions and chemical shifts of alkyl hydroxyl oxygen and alkyl fluorine nuclei

Abstract The correlation between the local steric van der Waals interactions as calculated by the MM2 force field and the chemical shift of the resonant nucleus has been extended to alkyl hydroxyl oxygen and alkyl fluorine. Root-mean-square errors corresponding to about 11 and 12%, respectively, of the total shift range are found. The extension of the model to two more elements of the first row strengthens its base and provides an explanation for known correlations between observed shifts in isostructural systems.
Helix−Coil Transition of a Four-Way DNA Junction Observed by Multiple Fluorescence Parameters

The thermal denaturation of immobile four-way DNA (“Holliday-”) junctions with 17 base pair arms was studied via fluorescence spectroscopic measurements. Two arms of the molecule were labeled at the 5′-end with fluorescein and tetramethylrhodamine, respectively. Melting was monitored by the fluorescence intensity of the dyes, the fluorescence anisotropy of tetramethylrhodamine, and Forster resonance energy transfer (FRET) between fluorescein and rhodamine. To fit the thermal denaturation curves of the four-way junctions, two basic thermodynamic models were tested: (1) all-or-none transitions assuming a molecularity of one, two, or four and (2) a statistical “zipper” model. The all-or-none models correspond to reaction mechanisms assuming that the cooperative melting unit (that is, the structure changing from complete helix to complete coil) consists of (1) one arm, (2) two neighboring arms (which have one continuous strand common to the two arms), or (3) all four arms. In each case, the melting of the coo...
Diffusion of self-interstitial atoms in silicon

Abstract Self-interstitial atoms are the principal point defects in silicon. These defects influence the diffusion of impurity atoms in silicon and their solubility. A method for the independent determination of the equilibrium concentration and of the diffusivity of these self-interstitials is suggested. In the framework of this approach some experimental results are discussed.
Age, growth and the potential for growth overfishing of spot (Leiostomus xanthurus) from the Chesapeake Bay, eastern USA

Spot (Leiostomus xanthurus) are a popular commercial and sport fish in the Chesapeake Bay region (USA), but have not been managed with age-based models because of a lack of information on vital rates. This study determined that transversely sectioned otoliths were the most appropriate structure to age spot, and subsequently used those ages to estimate biological parameters and evaluate the potential for growth overfishing. Because spot are short-lived, this study explored estimating population parameters using both whole annulus counts and fractional ages. Although fractional ages may be more realistic, parameters estimated using fractions of a year should be interpreted with caution. Growth of spot was rapid (84% of length attained in the first year), the natural mortality rate was high (59% year−1), and the total mortality rate (natural + fishing) was very high (80–94% year−1). Spot maximised cohort biomass early in life (≈1 year) and were relatively impervious to growth overfishing. This study illustrates the difficulty in providing management advice for species that maximise cohort biomass about the same time as their first potential spawning event. This study also documents that high exploitation rates and size selective fishing gear probably affect estimates of population parameters.
Gas-Phase and Solution-Phase Homolytic Bond Dissociation Energies of H-N(+) Bonds in the Conjugate Acids of Nitrogen Bases.

The oxidation potentials of 19 nitrogen bases (abbreviated as B: six primary amines, five secondary amines, two tertiary amines, three anilines, pyridine, quinuclidine, and 1,4-diazabicyclo[2,2,2]octane), i.e., Eox(B) values in dimethyl sulfoxide (DMSO) and/or acetonitrile (AN), have been measured. Combination of these Eox(B) values with the acidity values of the corresponding acids (pKHB+) in DMSO and/or AN using the equation: BDEHB+ = 1.37pKHB+ + 23.1 Eox(B) + C (C equals 59.5 kcal/mol in AN and 73.3 kcal/mol in DMSO) gave estimates of solution phase homolytic bond dissociation energies of H−B+ bonds. Gas-phase BDE values of H−B+ bonds were estimated from updated proton affinities (PA) and adiabatic ionization potentials (aIP) using the equation, BDE(HB+)g = PA + aIP − 314 kcal/mol. The BDEHB+ values estimated in AN were found to be 5−11 kcal/mol higher than the corresponding gas phase BDE(HB+)g values. These bond-strengthening effects in solution are interpreted as being due to the greater solvation ...
Kilometre-scale structures in the Sun's corona

Knowledge of the structure of the Sun's corona is important for our understanding of how this high-temperature plasma is heated, and of the processes involved in the acceleration of the solar wind. The structure can be investigated directly by imaging at optical and shorter wavelengths, or indirectly through the effects of changing electron density on the propagation of radio waves (scattering and scintillation). Radio measurements have established many of the characteristics of the density fluctuations in the corona and solar wind, but the fundamental nature of these structures is not yet fully understood. Two specific features that have proved difficult to explain are an abrupt increase in anisotropy of the irregularities close to the Sun, and a break in the power-law spectrum describing the density fluctuations. Here I argue that these features are the manifestation of a transition from small ray-like or filamentary structures in the corona that rotate with the Sun to turbulent density irregularities convecting with the solar wind. I estimate the size of the smallest filamentary structure within coronal holes to be about I km at the Sun, approximately three orders of magnitude smaller than the smallest filamentary structures observed in images of different wavelengths.
International Continuing Medical Education: A Paradigm for Grassroots Development

Pediatric care providers in the developing world face daunting challenges, often exceeding available resources. This challenge presents an opportunity for constructive involvement in international medicine by pediatric emergency medicine (PEM) physicians. The significant need for providing improved pediatric care worldwide dovetails with a high level of interest in international medicine among medical students, residents, and practicing physicians in the United States and Canada. With its emphasis on acute management and resuscitation, PEM specialists possess a knowledge base and skill set vital to pediatric care in the developing world. Development of collaborative continuing medical education is an important step in the improvement of pediatric emergency care in the developing world. A paradigm of successful program development is discussed based on experiences in Guatemala and Ghana. Future directions in international continuing medical education, including enhanced PEM fellow involvement, are also discussed.
Structures and Free Energy Landscapes of the A53T Mutant-Type α-Synuclein Protein and Impact of A53T Mutation on the Structures of the Wild-Type α-Synuclein Protein with Dynamics

The A53T genetic missense mutation of the wild-type α-synuclein (αS) protein was initially identified in Greek and Italian families with familial Parkinson’s disease. Detailed understanding of the structures and the changes induced in the wild-type αS structure by the A53T mutation, as well as establishing the direct relationships between the rapid conformational changes and free energy landscapes of these intrinsically disordered fibrillogenic proteins, helps to enhance our fundamental knowledge and to gain insights into the pathogenic mechanism of Parkinson’s disease. We employed extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations to determine the secondary and tertiary structural properties as well as the conformational free energy surfaces of the wild-type and A53T mutant-type αS proteins in an aqueous solution medium using both implicit and explicit water models. The confined aqueous volume effect in the simulations of disordered proteins using an explici...
Influence of Different Unifloral Honeys on Heterocyclic Aromatic Amine Formation and Overall Mutagenicity in Fried Ground-beef Patties

The effects of different unifloral honeys (buckwheat, clover, and sage), carbohydrates (fructose, glucose, and sucrose), and antioxidants (vitamin E, BHT), and Trolox® (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) on heterocyclic aromatic amine (HAA) formation and overall mutagenicity in fried ground patties were evaluated. The inhibition of total HAA formation was achieved with buckwheat (55%), clover (52%), and sage (51%); and they also reduced overall mutagenicity 36, 31, and 26%, respectively. The addition of fructose, glucose, or fructose and glucose together, at levels comparable to their occurrence in honey, reduced (p < 0.05) mutagenicity and HAA formation by amounts comparable to that found with honey.
Neuronal ‘differentiation’ of murine neuroblastoma cells induced by neocarzinostatin: neural cell adhesion molecules

Abstract Neural crest tumor cells which have been pharmacologically induced in culture to undergo neuronal ‘differentiation’ have been proposed as a model for normal neural crest cell differentiation. We have previously reported that murine neuroblastoma cells treated with the antineoplastic agent neocarzinostatin (NCS) adopt the light microscopic appearance of differentiated neurons. After undergoing morphologic change, the cells no longer divide. As part of an effort to compare the process of differentiation in these cells with what is known about normal neural crest cells, we have examined the cellular distribution and isoform complement of neural cell adhesion molecules (NCAMs) in native and NCS-treated neuroblastoma cells. Our studies show that NCS induces profound changes in NCAM distribution. Immunohistochemical staining indicates that, in contrast to native neuroblastoma cells, more than 80% of treated cells display surface NCAM by 4 days following treatment. Unlike the case for normal neurons, NCAM is uniformly distributed over the treated cell surface. Neuroblastoma cells treated with NCS are more avidly adherent to culture plates coated with NCAM than are control neuroblastoma cells, reflecting the homophilic binding characteristics of NCAM. Interestingly, Western blot analysis for NCAM demonstrates similar total cellular content of a single NCAM species in both control and treated neuroblastoma cells. Furthermore, this 120 kDa mol. wt. NCAM is an isoform of NCAM not found on normally differentiated cerebellar neurons. While the presence of NCAM on these treated murine neuroblastoma cells is evidence for ‘differentiation’ along neuronal lines, the isoform complement and cell surface distribution of NCAM in treated cells are not normal. The change in surface staining for NCAM without a change in the total amount of NCAM suggests a redistribution of NCAM within the cell. This is supported by our finding that, while untreated cells do not stain superficially for NCAM, permeabilization of these cells leads to marked staining, implying that, upon treatment, cytoplasmic NCAM is translocated to the membrane.
Gastroesophageal Reflux-induced Bronchoconstriction: An Intraesophageal Acid Infusion Study Using State-of-the-Art Technology

Study objective To study mechanisms of gastroesophageal reflux-induced bronchoconstriction during intraesophageal infusions. Design Prospective study blinded to the subject. Setting Outpatient pulmonary function laboratory at a 908-bed university hospital. Participants Forty-seven adult subjects divided into four groups: asthmatics with reflux, 20; asthmatics, 7; gastroesophageal refluxers, 10; and normal controls, 10. Asthmatics were defined by American Thoracic Society criteria, and refluxers were defined by symptoms and 24-hour pH monitoring. Interventions Dual antimony esophageal pH probe placed just below the upper esophageal sphincter and 5 cm above the lower esophageal sphincter. Intraesophageal infusions of normal saline solution followed by 0.1N hydrochloric acid then normal saline solution were given for 15 to 18 min. Spirometry and specific airway resistance (SRaw) were performed after placement of pH probes, insertion of esophageal infusion tube, and after each infusion. Bernstein tests were assessed during esophageal infusions. Measurements and results Peak expiratory flow rate (PEF) decreased with intraesophageal acid in all four groups (p Conclusions Intraesophageal acid infusions caused a decrease in PEF in all groups without evidence of microaspiration, implying a vagally mediated reflex may be involved. Esophageal mucosal inflammation, assessed by a positive Bernstein test, was not required. Asthmatics with reflux also had further decline in PEF despite acid clearance.
Personal Accounts of Successful Versus Failed Attempts at Life Change

Subjects (N = 119) wrote stories about successful or failed life change experiences. Stories reporting successful change attempts were more likely than stories reporting failed attempts to mention intense emotional experiences, external threats, and focal events that often culminated in crystallizations of discontent. These events were related to reevaluations of goals and life meaning and increased motivation to change. Social support, attributions of internal control, blaming external events for failure, and the development of a new sense of identity that incorporated the changed behavior were strongly associated with reports of successful change. Failure narratives were more likely than success narratives to describe change in terms of willpower and to indicate an active participation in maintaining the status quo. These results provide a glimpse at the phenomenology of life change attempts.
Intraindividual Relationships between Serum Protein Binding of Drugs in Normal Human Subjects, Patients with Impaired Renal Function, and Rats

The serum protein binding of phenytoin, salicylic acid, sulfisoxazole, and warfarin was determined in normal human adults, in patients with impaired renal function (kidney donor and recipient), and in adult male Sprague-Dawley rats. The free fraction values for salicylate and sulfisoxazole were significantly correlated in all three groups. The other correlations were statistically significant in only one or two of these groups. There was a statistically significant negative correlation between albumin concentration and the free fraction values of salicylic acid and sulfisoxazole (but not of phenytoin and only under special circumstances with warfarin) in normal human subjects and of phenytoin, salicylic acid, and sulfisoxazole (but not warfarin) in rats. No such correlation was observed for any of the drugs in patients with impaired renal function. These observations show that no single weakly acidic drug can serve as an index for quantitatively determining the effect of disease or species differences on the serum protein binding of other weakly acidic drugs.
The Sister (Mary) Joseph nodule: its significance in gynecology

Twenty-five cases of metastatic carcinoma of the umbilicus in women diagnosed and treated at Emory University Hospitals from 1973 to 1989 were reviewed, as were all previously reported cases in the English language literature. In our series, overall survival was greatest in patients treated with aggressive surgery and chemotherapy, compared with patients receiving no therapy or those treated with either surgery or adjunctive therapy alone. Individual survival was enhanced when the primary tumor site was of ovarian origin.
High School Accountability: The Role of Perceived Collective Efficacy

This study examined the relationship between collective efficacy and high school student achievement in a state with an accountability system heavily focused on achievement, measured by mandatory assessments in multiple content areas. Using social cognitive theory, a theoretical model was developed linking school context and collective efficacy to differences among schools in 12th grader student achievement. Structural equation modeling was used to test the fit of the model to data drawn from students and teachers in 96 state high schools. Collective efficacy was positively influenced by past mastery experience and negatively related to school socioeconomic disadvantage. Additionally, after accounting for the influence of several aspects of school context, collective efficacy remained a significant positive predictor of student performance across all content areas tested by the state. The authors discuss the implications of these findings for social cognitive theory and school improvement in an era of sch...
Agriculture and water pollution

The attempt by certain jurisdictions to preserve a rural lifestyle by means of farmland preservation may produce some unwanted side effects, such as polluted water supplies. While there are many excellent and important reasons to preserve high-quality agricultural land for food production, efforts to retain or encourage agricultural activities in areas experiencing rapid population growth may produce some serious environmental problems. For the entire post-WW II period the United States has experienced almost continuous suburban sprawl. Many incorporated areas, experiencing rapid development, have attempted to preserve open-space and less-developed land uses by actively attempting to preserve agricultural activities. Often the most recent migrants to a growing municipality exemplify the ‘last in’ syndrome by being among the most vociferous in attempting to halt further development.