cssi/SciSciGPT-SciSciNet huggingface dataset:
Real-time chemical analysis of aerosol particles using an ion trap mass spectrometer

Chemical analysis of aerosol particles in real time has been demonstrated using laser desorption mass spectrometry in an ion trap. Airborne particulates were extracted from the air directly into a vacuum system through a capillary and a skimmer with differential pumping. The injected particles were detected individually at two positions by fiberoptic based optical detectors. The velocity of the particle was estimated by the time difference between them and used to predict the arrival time at the center of the ion trap, so that a Nd:YAG laser could be fired exactly on time to desorb/ablate the particle. The desorbed and ionized species from the microparticle were analyzed by the ion trap mass spectrometer (ITMS). The sample aerosol particles were generated by nebulizing salt solution into the air through an orifice with a Piezoelectric vibrator. Mass spectra of potassium nitrate particles with a size of 15 Am in diameter extracted directly from the air have been measured. The velocity distribution of potassium nitrate particles (15{mu}m) extracted through a capillary with a inner diameter of 0.5 mm was found to have a maximum at 160 m/s. The electronic timing control system that measures the velocity of the individual microparticle and triggers themore » desorption laser to intercept the fast moving microparticle will be discussed.« less
Activated Sludge Treatment of Poultry Processing Wastewater

Abstract Wastewater from a poultry processing plant was treated with activated sludge in a laboratory-scale system. Results of the study showed that the activated sludge method was feasible and that it removed more than 90% of the chemical oxygen demand (COD), suspended solids and fat. Overall performance and sludge settling characteristics were best at a sludge age of 2 to 3.5 days.
Many-atom screening effects on diffusion in dense helium.

The structure and dynamics of helium at 5 eV over the density range 1.5{le}{rho}{le}8 g/cm{sup 3} were studied using self-consistent-field molecular dynamics. Representative results for the pair-correlation function, velocity autocorrelation function, and the average charge density surrounding an atom are presented. Many-atom screening is found to have an important effect on all of these quantities above 0.3 g/cm{sup 3}. Above 2 g/cm{sup 3}, screening effects appear to saturate, and the coefficient of diffusion tends to the limit of a one-component plasma.
Posterior vitreous detachment: evolution and complications of its early stages.

Purpose To summarize emerging concepts regarding the onset and progression, traction effects, and complications of the early stages of age-related posterior vitreous detachment (PVD). Design Interpretive essay. Methods Review and synthesis of selected literature, with clinical illustrations, interpretation, and perspective. Results Imaging of the vitreoretinal interface with optical coherence tomography has shown that PVD begins in the perifoveal macula. Recent longitudinal studies have demonstrated conclusively that early PVD stages persist chronically and progress slowly over months to years. Vitreous traction forces resulting from perifoveal PVD with a small vitreofoveolar adhesion (500 μm or less) may cause localized cystoid foveal thickening or one of several macular hole conditions. Traction associated with larger adhesion zones may cause or exacerbate a separate group of macular disorders. Ultrastructural studies suggest that epiretinal membrane develops from cortical vitreous remnants left on the retinal surface after PVD and plays an important role in traction vitreomaculopathies. Conclusions Age-related PVD is an insidious, chronic event that begins in the perifoveal macula and evolves over a prolonged period before vitreopapillary separation. Although asymptomatic in most individuals, its early stages may be complicated by a variety of macular and optic disc pathologic features, determined in part by the size and strength of the residual vitreoretinal adhesion.
Understanding Middle School Students’ Physical Activity and Health-Related Quality of Life: An Expectancy-Value Perspective

Assessing and promoting physical activity and health-related quality of life (HRQOL) have become major public health issues, but little is known regarding HRQOL and its relation with physical activity in adolescents. This study attempted to examine relationships among middle school students’ motivation, physical activity, and HRQOL by using the expectancy-value model as a theoretical framework. Participants were 282 middle school students who responded to a previously validated inventory assessing their motivation, physical activity, and HRQOL. Correlation analyses revealed that expectancy-related beliefs and task values were positively related to physical activity and HRQOL. Physical activity was positively associated with physical, emotional, and social functioning of HRQOL. Regression analyses showed a significant relationship between increasing expectancy-related beliefs and increasing degrees of HRQOL. This research line is promising in that it can provide useful information regarding the translation of theory to practice in influencing adolescents’ physical activity and HRQOL.
Uranus photochemistry and prospects for Voyager 2 at Neptune

CH4 is the only photochemically active constituent in the atmospheres of Uranus and Neptune. NH3, H2O and H2S are all removed by condensation at pressures greater than 1.5 bars. Although the bulk mole fraction (about 2 percent) of CH4 is 20-30 times its solar value on both planets, it drops to its saturation limit (about 0.0001) at the Uranus tropopause, but remains high (about 2 percent) at the Neptune tropopause. This results in much greater mixing ratios of the product hydrocarbons in the stratosphere of Neptune. On both planets, the photolysis products of CH4 undergo condensation near the tropopause and the upper stratosphere. Voyager observations of the hydrocarbons at Uranus and those planned at Neptune are discussed, along with their implications for upper-atmospheric physics and thermochemistry.
Food Problems and Emerging Policy Responses in Sub-Saharan Africa

Sub-Saharan Africa currently faces serious food problems manifested in declining per capita food production, chronic malnutrition, rising food aid requirements, and growing food imports. There are basic weaknesses in the structure of food production, the performance of official marketing systems, infrastructure, and government policies in most sub-Saharan countries. During the last decade, these weaknesses were highlighted by rising demand and by a series of physical, economic, and political shocks which brought major food crises that governments could not ignore. Governments responded by making increased food self-reliance a major national objective and by formulating strategies for increasing domestic food production. Several countries recently have made policy changes to stimulate local food production, with mixed results. This paper will (a) characterize contemporary African food problems and highlight their longer-term implications, (b) provide information on emerging policy responses, and (c) identify the food policy issues raised by these policies.
Testing Vision-Based Sensors for Enclosed Underwater Environments When Applied to EKF SLAM

Robotic vehicles working in unknown environments require the ability to determine their location while learning about obstacles located around them. A classic approach to solving this problem is feature-based Simultaneous Localization and Mapping (SLAM) using an Extended Kalman Filter (EKF). In this paper, feature-based EKF SLAM is used to examine the feasibility of using a low cost vision-based sensor for performing SLAM in enclosed underwater environments. Classic acoustic-based range sensors suffer from poor performance in enclosed areas due to reflections, furthermore the relatively high cost of acoustic-based navigation sensors prevents their use on low cost underwater vehicles. To overcome these challenges, a custom vision-based range finder and a downward facing camera for the implementation of a standard feature tracking algorithm are used to perform EKF SLAM.Copyright © 2012 by ASME
Structural and immunochemical characterization of human urine arylsulfatase A purified by affinity chromatography.

Abstract Arylsulfatase A (aryl-sulfate sulfohydrolase, EC 3.1.6.1) was isolated from an ammonium sulfate precipitate of urinary proteins using two different affinity chromatography methods. One method involved the use of concanavalin A-Sepharose affinity chromatography at an early stage of purification, followed by preparative polyacrylamide gel electrophoresis. The other procedure employed arylsulfatase subunit affinity chromatography as the main step and resulted in a remarkably efficient purification. The enzyme had a specific activity of 63 U/mg. The final preparation of arylsulfatase A was homogeneous on the basis of polyacrylamide gel electrophoresis at pH 7.5 and by immunochemical analysis. However, when an enzyme sample obtained by either method of purification was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing or non-reducing conditions, peptide subunits, of 63.5 and 54.5 kDa, were observed. Immunological tests with 125I-labeled enzyme established the presence of a common protein component in both of the electrophoretically separable peptide subunits of human urine arylsulfatase. The amino acid analysis of homogeneous human urine arylsulfatase A showed only a few differences between it and the human liver enzyme. However, immunological cross-reactivity studies using rabbit anti-human urine arylsulfatase revealed immunological difference between the human urine and liver arylsulfatase A enzymes.
CD40L (CD154) expression in human liver allografts during chronic ductopenic rejection

The CD40-CD40L (CD154) interaction plays a pivotal role in the effector mechanisms of allograft rejection. Blockade of the CD40/CD40L costimulatory pathway prevents the development of chronic allograft rejection in several animal transplant models. The relevance of in situ CD40 and CD40L expression in human liver allografts was assessed by immunohistochemistry during ductopenic chronic rejection (CR). In CR allograft specimens (n = 8), marked CD40L expression was detected on Kupffer cells (KCs) and sinusoidal macrophages with a unique centrilobular distribution (P < .001). The CD40L+ KCs and macrophages were shown to be CD68+ after immunohistochemical analysis of serial sections with anti-CD68 monoclonal antibody. Moderate staining of vascular and sinusoidal endothelial cells and mononuclear infiltrates was observed in some CR cases. These findings were in contrast to the absence of CD40L expression in controls (n = 11) consisting of stable liver allograft and normal liver tissue specimens. Only occasional CD40 expression in some cases of CR and controls was observed. In CR, CD40L (CD154) expression is manifested on KCs and macrophages. The present novel data show another important cellular source of CD40L expression and suggest a potential role of KCs/macrophages and CD40/CD40L costimulatory interactions in the pathogenesis of chronic rejection ductopenic liver allograft.
Pregnancy loss and thrombosis with protein C deficiency.

Abstract OBJECTIVES : Protein C inhibits coagulation and promotes fibrinolysis. This study investigates the association between protein C deficiency and pregnancy loss, thrombosis in pregnancy, and thrombosis with oral contraception. STUDY DESIGN : Fifteen protein C-deficient patients and 37 controls from a single kindred were studied. An obstetric history was obtained by telephone. Data were analyzed by logistic regression, Fisher's exact test, and Student t test. RESULTS : Protein C-deficient women experienced a 33% pregnancy loss versus 19% in the controls (not significant). Thromboembolism during pregnancy in protein C-deficient women was 33% (45% in those not receiving prophylactic anticoagulation) versus 5% in controls (odds ratio 7.37, p = 0.026). Five of 12 protein C-deficient women using oral contraception developed thrombosis versus 0 of 33 controls. The risk of thrombosis for protein C-deficient women using oral contraception is increased ( p CONCLUSIONS : Perinatal outcome is not statistically different with protein C deficiency. Protein C deficiency increases the risk of thrombosis during pregnancy and with oral contraception. Prophylactic heparin is suggested during pregnancy for protein C-deficient women with personal or family histories of thrombosis. Oral contraception is not advised. (Am J Obstet Gynecol 1992;167:968–72.)
How Far Do Cosmic Rays Travel

Two entirely different suggestions have been advanced in the literature as to where the cosmic rays originate. The first suggestion is that cosmic rays are of local origin (upper earth atmosphere, our own planetary system, etc.). The other suggestion is that cosmic rays are produced or have been produced throughout the universe, or even more specifically, throughout interstellar or intergalactic spaces. This latter view has especially been advanced by R. A. Millikan.
Advances in digital power control

This paper introduces recent advances in digitally controlled DC/DC switching converters. Three main blocks appear in almost every digital controller: the eADC, the digital compensator, and the DPWM. The implementation and different structures of these blocks are explained. Compensator design and some nonlinear control techniques that improve the performance of the switching converters are discussed. Experimental and simulation results are provided to validate the design techniques.
The effect of smoothing functions on data obtained from a FFT

This research investigated the effect on power spectra when data-smoothing functions were used on EEG data prior to submitting them to a FFT. We used two smoothing function options: not using any smoothing function and using the Parzen smoothing function. We developed a program to evaluate each of these functions with real and standard data. When a set of data is submitted to smoothing prior to being submitted to a FFT, there are statistically significant differences in the power spectra obtained from the FFT. This finding holds true for standard waveforms as well as for real EEG data.
Duration of relative protection of screening for cervical cancer.

Abstract The reduction in cervical cancer among women with at least one previous negative Pap smear can be assessed in terms of the time elapsed since the last smear was taken. One indicator of the utility of screening is the duration of relative protection, commonly calculated as the inverse of the disease odds ratio. Most investigations of the extent of relative protection provided by Pap testing have relied on data from centrally organized screening programs or case-control studies. For geographic areas without mass screening programs or tumor registries, reliance on subject recall of Pap tests is required. We conducted a case-control investigation of cervical cancer and interviewed 153 Maryland women with invasive disease and two control groups: 153 case-nominated controls and 392 randomly selected controls. The duration of relative protection of screening for disease was 4–6 years for both control groups [relative protection (RP) = 4.30, 95% confidence interval (CI) = 1.5–12.7 for neighborhood controls, RP = 3.63, 95% CI = 1.4–9.6 for random controls]. These findings held after adjusting for education, ever treated for a sexually transmitted disease, smoking, age at menarche and at first sexual intercourse, number of pregnancies, lifetime contraceptive use, and utilization of obstetrician-gynecologist services; the RPs increased upon adjustment. However, there was a decline in the RP with increased duration. Our findings are directly comparable to reports where smears have been verified, suggesting that self-reports of previous tests may be reliable as a method to evaluate the utility of screening.
Visions of Odalisques: Orientalism and Conspicuous Consumption in Leila Sebbar's "Le peintre et son modèle" (2007)

Many Algerian writers (Alloula, Djebar, Boudjedra) have revisited the representational politics of colonial iconography despite awareness that this endeavor is at risk of renewing exoticism. This article examines how Leila Sebbar’s “Le peintre et son modele” reproduces such a problematic stance through the inclusion of a photograph by Joel Leick inline with her short story. Whereas Sebbar attempts to deconstruct the photograph’s orientalism by placing it outside the realm of the aesthetic and resituating it within the sexual exploitation of women in the former French colonies, I intend to demonstrate how this photograph reintroduces the very inequalities that her text tries to evacuate. Leick’s model elicits an eroticized gaze from readers, who become onlookers and obedient participants in the neocolonial consumption process. Rereading Sebbar’s short story through the lens of this photograph thus shows current limitations to the power of postcolonial texts and, ultimately, their troubled dependence on orientalist iconography.
Forward masking and unmasking of the offset cochlear compound action potential of the gerbil: comparison with suppression areas of the onset cochlear compound action potential.

Abstract Simultaneous and forward maskers were used to generate ‘onset’ and ‘offset’ compound action potential tuning curves (TCs) in the gerbil. The simultaneously masked offset TC, generated in response to a 16 kHz, 65 dB SPL probe stimulus, is W-shaped, with a low frequency tip at 11 kHz, a high frequency tip at 20 kHz. and a peak which occurs at 16 kHz. The 16 kHz forward masked onset TC has a single tip which occurs at 11 kHz. Although it lacks the finely tuned peak and high frequency tip of the stimultaneously masked offset TC, its single tip is more finely tuned than the low frequency tip of the simultaneously masked offset TC. Normalizing these two TCs [(1977) J. Acoust. Soc. Am. 62, 1048–1051] produces a figure which resembles 11 kHz onset TCs with their nonoverlapping regions which are analogs of two-tone suppression (2TS). A similar pattern occurs when probe stimuli at frequencies from 13 to 24 kHz are used to generate offset TCs; i.e., the forward masked offset TC resembles an onset TC and normalizing it to a simultaneously masked offset TC produces areas which resemble analogs of 2TS. Unmasking of the forward masked onset TCs [(1979) Hear, Res. 1, 133–154] produces regions of 2TS which are very similar to those produced by unmasking the forward masked offset TC which is generated by a higher frequency tone. These regions of 2TS for the Offset TC, as determined by unmasking, are very similar to the analogs of 2TS described above.
Dry etching of GaAs with Cl2: correlation between the surface Cl coverage and the etching rate at steady state

Abstract While dry etching of GaAs with chlorine is technologically important for manufacturing semiconductor devices, little is known conclusively about the surface chemical reactivity responsible for this etching process. In this work, modulated molecular beam scattering (MMBS) has been combined with temperature-programmed reaction (TPR) and Auger electron spectroscopy (AES) to study the reaction of molecular chlorine with GaAs. The MMBS and AES results indicate that the surface coverage of chlorine during steady state etching over the temperature range of 350–650 K is in the monolayer regime. Above 700 K the surface is chlorine free. A direct correlation is observed between the number of vacant surface sites and the Cl2 reaction probability. This result suggests a Langmuir adsorption model for the surface reaction, and it is shown that such a model combined with the product evolution kinetics determined from TPR studies successfully simulates the temperature dependence of the chlorine evolved from the surface during modulated molecular beam scattering.
Fetal thymocyte potential for T cell receptor Vγ3-Jγ1 junctional modification

Junctional modifications of T cell receptor (TcR) and immunoglobulin (Ig) gene joining regions provide great diversity to respective protein repertoires. The addition of non-germ-line-encoded nucleotides (N-regions) in the V-J gamma junction is one such modification which is developmentally regulated, rarely evident in the fetal animal, but common in the adult. A question has recently arisen as to whether developmentally patterned N-region additions in V-J gamma joins are a reflection of T cell progenitors which are committed to particular types of rearrangement prior to the event, or of changing environmental influences on uncommitted cell populations. To address this question with regard to the V gamma 3-J gamma 1 join, T cells were examined in the fetal thymic organ culture (FTOC), a system with which the environment of early progenitor cells could be deliberately altered. At various times following FTOC initiation, cells were isolated for examination by the polymerase chain reaction, cloning and sequencing. V gamma 3-J gamma 1 sequences within genomic DNA as well as cDNA were evaluated. Data from these studies revealed frequent N-region additions within V-J gamma joins among day 14 fetal thymocyte populations, a situation dissimilar from that in vivo. Also dissimilar from the in vivo situation was the degree of exonuclease activity evident in FTOC. The canonical V gamma 3-J gamma 1 join (a frequent junction lacking N-region addition) was recognized in all experiments, but was least common among DNA versus cDNA sequences. Results illustrate that early progenitor cell populations are not programmed to exclude junctional modifications from V gamma 3-J gamma 1 joins.
Pharmacotherapy of compulsive hoarding

Compulsive hoarding is a common and potentially disabling disorder. This article reviews studies of the effects of hoarding on response to serotonin reuptake inhibitor (SRI) medications in patients with obsessive-compulsive disorder (OCD), as well as recent studies of pharmacotherapy specifically for patients with the compulsive hoarding syndrome. Taken together, the results of these studies indicate that the "conventional wisdom" that compulsive hoarding does not respond well to SRI treatment is wrong. SRIs appear to be as effective for compulsive hoarders as for nonhoarding OCD patients. A case is presented of a compulsive hoarding patient who responded well to pharmacotherapy with a novel agent. Symptom improvement from pharmacotherapy of compulsive hoarding appears to be at least as great as that resulting from cognitive-behavioral therapy (CBT). However, the combination of pharmacotherapy and CBT for compulsive hoarding is likely more effective than either treatment alone.
Lyapunov stability criteria for zonal adaptive-optics systems

Lyapunov stability criteria are derived for a first-order closed-loop adaptive-optics servo system, resulting in a linear matrix equation that includes the system geometry, servo parameters, and wave-front reconstruction matrix. It is demonstrated that instability zones depend on the choice of matrix estimator and the servo-loop gain. Divergence of the error propagator gives results that are consistent with the Lyapunov equation. The significance of these results is discussed.
Chlorpromazine methiodide acts at the vestibular nuclear complex to induce barrel rotation in the rat.

Barrel rotation is a unique motor response observed in rats in which, following an intracerebral injection, the animal develop a twist about the long axis and rolls laterally repeatedly. The response was first described following injection of somatostatin. We have previously shown that ‘experimental dystonia’ in rats induced by intraventricular chlorpromazine methiodide (CPZMI) is identical to barrel rotation, and that it is due to an antimuscarinic effect. The purpose of the present study was to investigate the neuroanatomical basis of CPZMI-induced rotation. We injected CPZMI in 3 μl into right lateral and IVth ventricle and found that IVth ventricle injections were significantly more likely to induced rotation. Nuclear groups adjacent to the IVth ventricle, which are rich in muscarinic cholinergic receptors, include locus coeruleus and vestibular nuclear complex (VNC). We found that only VNC injections induced rotation. Only certain control compounds injected into VNC elicited the response. We conclude that barrel rotation has a specific neuroanatomical basis, involving central vestibular mechanisms, and that it has a specific pharmacologic basis.
Could firewall rules be public – a game theoretical perspective

Firewalls are among the most important components in network security. Traditionally, the rules of the firewall are kept private under the assumption that privacy of the ruleset makes attacks on the network more difficult. We posit that this assumption is no longer valid in the Internet of today due to two factors: the emergence of botnets reducing probing difficulty and second, the emergence of distributed applications where private rules increase the difficulty of troubleshooting. We argue that the enforcement of the policy is the key, not the secrecy of the policy itself. In this paper, we demonstrate through the application of game theory that public firewall rules when coupled with false information (lying) are actually better than keeping firewall rules private, especially when taken in the larger group context of the Internet. Interesting scenarios arise when honest, public firewalls are socially insured by other lying firewalls and networks adopting public firewalls become mutually beneficial to each other. The equilibrium under multiple-network game is socially optimal because the percentage of required lying firewalls in social optimum is much smaller than the percentage in single-network equilibrium and the chance of attacking through firewalls is further reduced to zero. Copyright © 2011 John Wiley & Sons, Ltd.
The effects of bonus contingencies in a classwide token program on math accuracy with middle‐school students with behavioral disorders

The effects of bonus points contingent on 80% accuracy in math with four middle-school special education students with behavior disorders were examined. A multiple-baseline design across students was used to evaluate the effects of bonus points. The overall results indicated that higher accuracy was found for math assignments during the bonus points condition than during baseline. This overall outcome was replicated for each subject in the study. The benefits of implementing a bonus contingency within an ongoing classroom token economy with middle-school students with behavior disorders are discussed. © 1998 John Wiley & Sons, Ltd.
The Genetics of Common Epilepsy Disorders: Lessons Learned from the Channelopathy Era

Idiopathic epilepsies are thought to be almost entirely the result of genetic determinants, most of which remain undiscovered. It was once widely accepted that mutations that change the amino acid sequence of ion channel proteins were the major cause of these epilepsies, making epilepsy in general a ''channelopathy.'' Since then, more comprehensive analysis of ion channel-encoding genes has largely rejected this hypothesis for common forms of epilepsy. Here, we discuss some of the assump- tions that led to the channelopathy hypothesis and propose ways to avoid similar mistakes going forward. We also offer insight into promising genetic candidates that we believe play a major role in susceptibility to common forms of idiopathic epilepsy.
Methoxyflurane: Effects upon cardiac contractility, rhythmicity, and blood pressure in dogs

Methoxyflurane was administered to unpremedicated dogs in increasing and decreasing cpncentrations while normal pulmonary ventilation was rigidly maintained. Myocardial contractility, blood pressure, pulse rate, electrocardiogram, and electroencephalogram were recorded continuously. A progressive decrease in contractile force of the heart muscle resulted as the inhaled concentration of methoxyflurane increased. A parallel decrease in systolic, diastolic, and pulse pressure occurred. Sinus bradycardia and an alteration in repolarization of cardiac muscle accompanied the dynamic changes. A lag occurred in recovery of all cardiovascular functions and the EEG following withdrawal of the agent. Burst suppression appeared when hypotension below 90 mm. Hg occurred. A comparison of the results of this study with those previously reported is presented.
Using Popular Films to Teach Systems Thinking

Making a paradigm shift from a linear perspective to a systemic perspective can present unique challenges to counseling students. Teaching students to make such a paradigm shift can be a challenge ...
Several remarks on the metric space of genetic codes

A genetic code, the mapping from trinucleotide codons to amino acids, can be viewed as a partition on the set of 64 codons. A small set of non-standard genetic codes is known, and these codes can be mathematically compared by their partitions of the codon set. To measure distances between set partitions, this study defines a parameterised family of metric functions that includes Shannon entropy as a special case. Distances were computed for 17 curated genetic codes using four members of the metric function family. With these metric functions, nuclear genetic codes had relatively small inter-code distances, while mitochondrial codes exhibited greater variance. Hierarchical clustering using Ward's algorithm produced a tight grouping of nuclear codes and several distinct clades of mitochondrial codes. This family of functions may be employed in other biological applications involving set partitions, such as analysis of microarray data, gene set enrichment and protein-protein interaction mapping.
Methamphetamine: A molecular and pathological exacerbate of HIV neurocognitive disorder

The use of the recreational drug methamphetamine is becoming more widespread, and it is accompanied by unsafe sexual behaviours that increase the transmission of the human immunodeficiency virus (HIV). This article reviews the available literature of the effect of methamphetamine on the HIV infected brain, and in particular the molecular disturbances and neuropathology associated within this cohort. Our molecular research indicates that methamphetamine and HIV have a synergistic pathological impact on neuronal cell injury and death, which may be mediated by an upregulation of interferon inducible genes observed within this group, thereby contributing to the neurocognitive deficits observed in clinical populations of HIV infected methamphetamine abusers.
Development of analytical and preparative chromatographic separations of novel growth hormone secretagogue compounds

Abstract Chromatographic separations of new growth hormone secretagogue compounds were developed to support structure–activity relationship (SAR) studies in conjunction with lead optimization. These new compounds differed from Merck’s MK-677 by having two chiral centers and thus diastereomeric mixtures were generated. Separation of initial compounds in the SAR was achieved on a Kromasil C18 column using an ammonium acetate buffer and acetonitrile. However, additional candidates were not separable on C18 columns and a chiral Kromasil CHI-DMB column was used to resolve the diastereomeric compounds. The Kromasil CHI-DMB packing was also used in a preparative chromatographic system to resolve multigram quantities of secretagogue candidates for testing. Chiral separations of different intermediates were also developed in support of evolution of an asymmetric synthetic route. This report summarizes development of the preparative chromatographic system used to purify diastereomeric mixtures and chiral separations of intermediates in the synthesis.
Quantifying the toxic and mutagenic activity of complex mixtures with salmonella typhimurium

The toxicity and mutagenicity of 11 compounds individually and in mixtures were quantified in Salmonella typhimurium strains TA98, TA100, and TA1537 by a modification of the Ames spot test. The distance (millimeters) from the center of the petri dish to the bacterial growth front represented the toxic response. When mutagenicity occurred, the distance from the inner radius to the outer radius of the mutagenic growth represented the mutagenic response. Multiple regression analysis was used to quantify the toxicity and mutagenicity of individual compounds in the mixtures. The results indicate that the effects of compounds in mixtures are generally additive.
The isolation and characterization of a calmodulin-encoding gene (CMD1) from the dimorphic fungus Candida albicans.

Abstract Candida albicans is a dimorphic, opportunistic pathogen of humans, and calcium and calmodulin have been implicated in its morphogenic transition. The C. albicans calmodulin-encoding gene, CMD1, was isolated from cDNA and genomic phage λ libraries using the Saccharomyces cerevisiae CMD gene as a hybridization probe. Southern-blot hybridization analysis of genomic DNA suggests the existence of only one type of calmodulin gene in C. albicans. Comparison of cDNA and genomic sequences identified a 222-bp intron located immediately after the Met start codon. The predicted amino acid sequence was 60% identical with yeast CMD and 70% identical with CMDs of filamentous fungi and vertebrates. We have localized the CMD1 gene to chromosome 3 using the contour-clamped homogeneous electric field gel electrophoresis. The CMD1 gene hybridized to a single 650-nucleotide transcript which was present in equivalent amounts in both the yeast and hyphal forms of the organism.
Evaluation of metal-mediated DNA binding of benzoxazole ligands by electrospray ionization mass spectrometry

The binding of a series of benzoxazole analogs with different amide- and ester-linked side chains to duplex DNA in the absence and presence of divalent metal cations is examined. All ligands were found to form complexes with Ni2+, Cu2+, and Zn2+, with 2:1 ligand/metal cation binding stoichiometries dominating for ligands containing shorter side chains (2, 6, 7, and 8), while 1:1 complexes were the most abundant for ligands with long side chains (9, 10, and 11). Ligand binding with duplex DNA in the absence of metal cations was assessed, and the long side-chain ligands were found to form low abundance complexes with 1:1 ligand/DNA binding stoichiometries. The ligands with the shorter side chains only formed DNA complexes in the presence of metal cations, most notably for 7 and 8 binding to DNA in the presence of Cu2+. The binding of long side-chain ligands was enhanced by Cu2+ and to a lesser degree by Ni2+ and Zn2+. The cytotoxicities of all of the ligands against the A549 lung cancer and MCF7 breast cancer cell lines were also examined. The ligands exhibiting the most dramatic metal-enhanced DNA binding also demonstrated the greatest cytotoxic activity. Both 7 and 8 were found to be the most cytotoxic against the A549 lung cancer cell line and 8 demonstrated moderate cytotoxicity against MCF7 breast cancer cells. Metal ions also enhanced the DNA binding of the ligands with the long side chains, especially for 9, which also exhibited the highest level of cytotoxicity of the long side-chain compounds.
Chapter 5 Vascular lesion formation

Abstract Interactions among cells of the blood vessel wall, blood cells, and materials probably contribute to certain reactive processes that limit the long-term success of a number of contemporary cardiovascular therapeutic interventions. For example, such interactions contribute to anastomotic hyperplasia following insertion of small caliber vascular prostheses and hyperplasia following insertion of intravascular stents. Blood-tissue interactions also probably contribute to restenosis following balloon or other types of angioplasty, saphenous vein bypass grafting, and the accelerated arteriosclerosis that complicates solid organ transplantation. Despite the diverse nature of the inciting interventions, common pathobiological mechanism may contribute to these tissue reactions. Signals arising from interactions between biomaterials and soluble or formed blood elements can modulate the functions of the cells that comprise the blood vessel wall. In many instances, altered endothelial function may play a primary or contributory role in vascular lesion formation. Migration and inappropriate proliferation of smooth muscle cells also commonly occur during reactions of blood vessels to interventional therapies. Increased accumulation of extracellular matrix materials and, sometimes, remodeling of this matrix often accompany smooth muscle migration and proliferation and participate in the formation of these vascular lesions. Such altered functions of vascular walls and their interactions with blood elements, including the coagulation system, platelets, and leukocytes, contribute to both initiation and progression of vascular lesions produced by cardiovascular interventions. Late in the natural history of these lesions, complications may arise that can yield significant clinical manifestations. Such complications include fissuring, rupture, ulceration, thrombosis and embolism, calcification of lesions and prosthetic devices, microvascular hemorrhage, and aneurysmal dilatation of vessels. These late complications often involve altered vascular cell functions related to interaction with soluble or formed elements of the blood and, when present, implanted biomaterials.
Comparison of Ultrasound Corticomedullary Strain with Doppler Parameters in Assessment of Renal Allograft Interstitial Fibrosis/Tubular Atrophy

To compare the capability of ultrasound strain and Doppler parameters in the assessment of renal allograft interstitial fibrosis/tubular atrophy (IF/TA), we prospectively measured ultrasound corticomedullary strain (strain) and intra-renal artery Doppler end-diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI) in 45 renal transplant recipients before their kidney biopsies. We used 2-D speckle tracking to estimate strain, the deformation ratio of renal cortex to medulla produced by external compression using the ultrasound transducer. We also measured Doppler EDV, PSV and RI at the renal allograft inter-lobar artery. Using the Banff scoring system for renal allograft IF/TA, 45 patients were divided into the following groups: group 1 with ≤5% (n = 12) cortical IF/TA; group 2 with 6%-25% (n = 12); group 3 with 26%-50% (n = 11); and group 4 with >50% (n = 10). We performed receiver operating characteristic curve analysis to test the accuracy of these ultrasound parameters and duration of transplantation in determining >26% cortical IF/TA. In our results, strain was statistically significant in all paired groups (all p 26%, including 26%-50% and >50%) and low-grade (≤25%, including 0.05). The areas under the receiver operating characteristic curve for strain, EDV, PSV, RI and duration of transplantation in determining >26% cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively. Our results suggest that corticomedullary strain seems to be superior to Doppler parameters and duration of transplantation in assessment of renal allograft cortical IF/TA.
Factors Affecting Individual's Intention to Purchase Smartphones from Technology Adoption and Technology Dependence Perspectives

The aim of this research is to identify factors affecting individual’s intention to purchase a Smartphone from the perspectives of technology adoption and technology dependence. This study takes into account the role of cell phone dependence and hedonic aspects of cell phone use, by combining technology acceptance model, diffusion of innovation theory and theory of optimal flow, in order to propose a new model for Smartphone purchase intention. The result of the study indicates that ‘cell phone dependence’, ‘enjoyment associated with using cell phone’ and ‘exposure to Smartphone’ have significant effects on ‘intention to use Smartphone’ which in turn positively affects ‘intention to purchase Smartphone’. This can justify the selfreinforcing increase in Smartphone purchases in recent years. The study concludes that the hedonic aspects of cell phone use and the degree of individuals’ dependence on cell phone are important factors attributing to their intention to purchase a Smartphone.
Treatment of equine glaucoma by transscleral neodymium:yttrium aluminum garnet laser cyclophotocoagulation: a retrospective study of 23 eyes of 16 horses.

Contact neodymium:yttrium aluminum garnet (Nd:YAG) laser transscleral cyclophotocoagulation (TSCP) was performed on 23 eyes of 16 horses for treatment of glaucoma. The mean highest preoperative IOP was 51 ± 17 mmHg. Follow-up evaluation was available for 19 eyes 1 day after surgery, 14 eyes from 1 to 2 weeks, 16 eyes from 4 to 6 weeks, 9 eyes from 12 to 16 weeks, and 10 eyes greater than 20 weeks after laser treatment. The mean intraocular pressure (IOP) the day following surgery was 34 ± 13 mmHg. The mean IOP for each follow-up period was: one to two weeks postoperative, 23 ± 9 mmHg; four to six weeks, 24 ± 7 mmHg; 12–16 weeks, 28 ± 10 mmHg; and 20 weeks, 22 ± 9 mmHg. IOP measurements were significantly different from pretreatment values for all follow-up intervals except for weeks 12–16 (P < 0.05). Treatment success was defined as maintenance of IOP < 30 mmHg. Treatment success was achieved in 93%, 88%, 78%, and 70% of the treated eyes at the 1–2 weeks, 4–6 weeks, 12–16 weeks, and the 20 weeks re-evaluation, respectively. No significant difference was found between the number of eyes visual at presentation (52.2%) and visual at 20 weeks (60%). The most common laser complications were conjunctival hyperemia (21.7%) and corneal ulcers (13.0%). Results of this study indicate that Nd:YAG TSCP is an effective method of controlling IOP and preserving vision in horses with glaucoma. An effective Nd:YAG laser protocol for TSCP in the equine glaucomatous eye is a power setting of 11 W, duration of 0.4 s, applied 5 mm posterior to the limbus at 60 sites, resulting in a total energy dose of 264 J.
Characterization of label‐retaining cells in the epidermis of a human skin equivalent

. The human skin equivalent (HSE) is an in vitro reconstructed model that resembles skin morphologically and biochemically. The HSE is formed by overlaying a fibroblast-populated collagen matrix with a suspension of epidermal cells. Basal keratinocytes attach to the dermal equivalent via a newly formed basement membrane and multiply to form a stratified, differentiated epidermis. The aim of the studies described here was to characterize the basal cells of the HSE in terms of their cell cycling potential. The experiments utilized long-term labelling of the cells with tritiated thymidine ([3H]dT), followed by irradiation with ultraviolet light. [3H]dT incorporation was analysed via routine autoradiography. Irradiation with 100 J/m2 UV light increased the number of labelled basal cells by 58% over the control, the maximal stimulation observed. Decreased numbers of labelled basal cells were observed at doses of UV light greater than 100 J/m2. The maximal number of labelled basal cells was observed on day 14 and decreased over time; the number of labelled suprabasal cells increased concomitantly. Label-retaining cells (12%) persisted in the stratum basale of control HSEs after 32 days in culture. Labelled cells were observed in the apical layers of the stratum granulosum of control HSEs after 22 days in culture. These data suggest that the stratum basale of the HSE contains a population of slow-cycling cells whose characteristics resemble a subpopulation of slowly cycling cells found in normal human skin.
Recent Ideas on Upgrading the SLAC Accelerator

In June 1971, the SLAC accelerator will have completed its first five years of operation. The machine has recently achieved records of energy (22.1 GeV), peak beam current (82 mA at a 1.6 ..mu..s pulse length) and average beam power (880 kW). The demand for major accelerator innovations and improvements is becoming increasingly strong. Some of the recent ideas on this subject are summarized. There are a variety of options, and these can be divided into three categories: (a) improvements and upgrading of the existing linac; (b) energy and duty cycle increases by means of beam storage in a recirculation scheme, and (c) various colliding beam devices. The first category includes increasing beam energy by addition of rf power or increasing duty cycle by modifying the modulators; it also includes an rf monochromatizer which could sharpen energy spectrum by a factor of 30. The second category involves a scheme which would increase beam energy by ''storing'' the electrons in a recirculator until they can be re-injected and reaccelerated by the accelerator a second time. The third category comprises the possibility of colliding the linac beam with the beams stored in the SLAC storage ring (SPEAR) or of colliding the linacmore » beam with itself.« less
Thinking in cycles: MWC is a good model for acetylcholine receptor-channels.

Abstract Neuromuscular acetylcholine receptors have long been a model system for understanding the mechanisms of operation of ligand-gated ion channels and fast chemical synapses. These five subunit membrane proteins have two allosteric (transmitter) binding sites and a distant ion channel domain. Occupation of the binding sites by agonist molecules transiently increases the probability that the channel is ion-permeable. Recent experiments show that the Monod, Wyman and Changeux formalism for allosteric proteins, originally developed for haemoglobin, is an excellent model for acetylcholine receptors. By using mutations and single-channel electrophysiology, the gating equilibrium constants for receptors with zero, one or two bound agonist molecules, and the agonist association and dissociation rate constants from both the closed- and open-channel conformations, have been estimated experimentally. The change in affinity for each transmitter molecule between closed and open conformations provides ∼–5.1 kcal mol−1 towards the global gating isomerization of the protein.
TACE/ADAM17 Processing of EGFR Ligands Indicates a Role as a Physiological Convertase

EGF family growth factors, including transforming growth factor-alpha (TGFalpha), amphiregulin (AR), and heparin-binding EGF (HB-EGF), are invariably expressed as transmembrane precursors that are cleaved at one or more sites in the extracellular domain to release soluble growth factor. Considerable attention has focused on the identification of proteases responsible for these processing events. We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane precursor, proTGFalpha. Here, we review our findings that primary keratinocytes from Tace(deltaZn/deltaZn) mice, which express a nonfunctional TACE, released dramatically lower levels of soluble TGFalpha compared to their normal counterparts, even though TGFalpha mRNA and cell-associated protein levels were similar in the two cell populations. Restoration of TACE activity in Tace(deltaZn/deltaZn) cells increased shedding of TGFalpha species, including the mature, 6-kDa protein. Further, exogenous TACE enzyme accurately cleaved the N-terminal processing site of proTGFalpha in cell lysates, as well as both physiologic sites of a soluble proTGFalpha ectodomain. TACE also accurately cleaved peptide substrates corresponding to the processing sites of several additional EGF family members, and restoration of TACE activity enhanced the shedding of soluble AR and HB-EGF proteins from Tace(deltaZn/deltaZn) cells. Finally, reduction of functional TACE gene dosage greatly exacerbated the open-eye defect of Egfr(wa-2/wa-2) newborns, which is regulated by redundant actions of several EGF family ligands. The implications of these results for the biology of the EGF family and TACE are discussed.