cssi/SciSciGPT-SciSciNet huggingface dataset:
Serotonergic afferents to the rat olfactory bulb: I. Origins and laminar specificity of serotonergic inputs in the adult rat.

This is a study of the chemoanatomical organization of the projection from the raphe nuclei to the main olfactory bulb in the rat. A heavy projection from the dorsal and median raphe nuclei to the main olfactory bulb was shown by both retrograde and anterograde tracing techniques. Following injections of 1% wheat germ agglutinin- horseradish peroxidase (WGA-HRP) into the main olfactory bulb, up to 1300 neurons were retrogradely labeled in the dorsal and median raphe nuclei, a much larger number than has been suggested by previous studies. By combining 5-HT immunofluorescence with True blue retrograde fluorescent labeling, it was determined that the vast majority of raphe neurons that project to the olfactory bulb contain serotonin. Injections of WGA-HRP into dorsal and/or median raphe produced dense anterograde labeling in the glomeruli, while fewer labeled fibers were observed in the external plexiform layer, internal plexiform layer, and granule cell layer. In contrast to the number of other centrifugal afferents to the bulb, a significant contingent of fibers from the raphe nuclei enters the main olfactory bulb (MOB) from outside in, i.e., via the olfactory nerve layer. Serotonergic fibers in MOB were visualized by immunocytochemistry, and the distribution of specific 5- HT fibers closely matched the distribution of anterograde terminal label resulting from injections of WGA-HRP in the raphe nuclei. The serotonergic fibers have a specific laminar distribution and morphology in MOB. Thus, the density of the serotonergic innervation to the glomerular layer is 2–3 times that of any other layer in MOB. In addition to their preferential innervation of the glomeruli, glomerular and infraglomerular serotonergic fibers are morphologically different. Serotonergic fibers located in the glomerular layer are generally thick (0.25–0.60 micron) compared to the thinner (0.25–0.35 micron) fibers that predominate in infraglomerular layers. Another difference is that the glomerular fibers often contain varicosities that are greater than 1 micron in diameter, while varicosities along infraglomerular fibers are usually barely larger than the axonal diameter. Finally, glomerular fibers are much more intensely stained than infraglomerular fibers. Electrolytic lesions of the dorsal and median raphe caused a total depletion of serotonin fiber staining in the bulb, demonstrating that the raphe nuclei are the sole source of the serotonergic input to the main olfactory bulb. Thus, it has been demonstrated that serotonergic neurons in dorsal and median raphe project very heavily to glomeruli and less heavily to other layers in the main olfactory bulb.(ABSTRACT TRUNCATED AT 400 WORDS)
FSH-releasing hormone and LH-releasing hormone.

Publisher Summary This chapter discusses the role of follicle-stimulating hormone (FSH)-releasing hormone and luteinizing hormone (LH)-releasing hormone. The involvement of the anterior pituitary in process of reproduction began with the discovery of gonadotropic activity in the pituitary. FSH stimulates the growth of the ovarian follicle by promoting mitotic proliferation of the granulosa cells. The response to FSH is demonstrable by the presence of follicles in all stages of development, initiation of antrum formation, and increase in ovarian weight. FSH is a gametogenic hormone in the male; it affects the function and structure of seminiferous tubules and production of spermatozoa. In the hypophysectomized rat and in hypophysectomized humans, FSH, given together with LH, stimulates spermatogenesis. The presence of androgens is necessary for full spermatogenesis. LH is responsible for stimulation of steroidogenesis in the ovarian follicle and for ovulation in the ovary previously stimulated by FSH and the transformation of the graafian follicles into corpora lutea. After ovulation, under the influence of LH, some granulosa cells increase in size and undergo the process of luteinization.
Adenosine Cyclic 3',5'-Monophosphate Concentrations during the Positive Inotropic Response of Cat Cardiac Muscle to Polymeric Immobilized Isoproterenol

Changes in cardiac contractility and concentrations of cyclic 3',5'-AMP in isolated cat papillary muscles in response to isoproterenol diazotized to a 12,800 mol wt random copolymer of hydroxypropylglutamine with p -aminophenylalanine (copoly-Iso) have been examined. It has been previously shown that copoly-Iso retains positive chronotropic and inotropic effects in perfused guinea pig hearts and isolated cat papillary muscles, respectively, without isoproterenol dissociation. In the present experiments, in isometrically contracting cat papillary muscles copoly-Iso (equivalent to 0.37 µmole of isoproterenol) resulted in prompt increases in the force and velocity of contraction within 20 sec. The copoly-Iso responses reached maximal levels by 180 sec and were similar in magnitude and time course to peak l -isoproterenol responses. Cat papillary muscles frozen 30-180 sec subsequent to copoly-Iso addition were subjected to cyclic AMP radioimmune assay. No detectable change in cyclic AMP concentrations were observed during increases in contractility (e.g., cyclic AMP control level was 5.54 ± 0.49 pmoles/mg of protein, n = 5). In contrast, papillary muscles frozen 60 sec after soluble l -isoproterenol addition had markedly increased cyclic AMP levels (11.56 ± 2.49 pmoles/mg of protein, n = 6). Gel permeation chromatography of muscle bath contents at the time of papillary muscle freezing indicated that no isoproterenol dissociated from the matrix during the experiments. These results confirm our previous findings for glass bead immobilized isoproterenol, where nearly maximal inotropic responses were obtained without detectable changes in cyclic AMP concentrations, and place further into question the role of cyclic AMP in catecholamine-induced beta receptor-stimulated cardiac contractility.
Alcohol and Alcoholism in Traffic and Other Accidental Deaths

To assess the role of alcohol and alcoholism in motor vehicle and other accidental deaths, New Jersey State Medical Examiner cases from Essex County aged 16 or older during a 4-year period, October 1981 to September 1985, were analyzed. Cases were classified as alcoholics according to the following criteria: (1) autopsy findings of liver change or pancreatitis due to alcoholism or (2) any case record report of drinking problems. There were 467 age-eligible cases whose certified manner of death was an accident for which the decedent may have had some responsibility. The study sample consists of 300 cases with blood or brain alcohol levels (BALs) obtained within 6 h after injury, including 96 motor vehicle drivers, 78 pedestrians in motor vehicle accidents, 38 fire victims, and 33 fall victims. In the study sample, 23% were classified as alcoholics, 47% had positive BALs, and 36% had levels of 0.10% or more. Alcoholics much more often than nonalcoholics had positive BALs and levels of 0.20% or more. Acciden...
Alvin W. Gouldner and industrial sociology at Columbia University.

Alvin W. Gouldner (1920–1980) was a prolific sociologist of the post-World War II era who spent the early part of his career (the 1950s) in the field of industrial sociology. A case study of Gouldner's early life and career is useful insofar as it intertwines with the development of industrial sociology as a distinct subfield within sociology. Through this analysis we are also better able to understand how and in what ways a burgeoning organizational studies program developed at Columbia University during the 1940s. This analysis of the historical and cultural contexts within which Gouldner came to prominence as an industrial sociologist at Columbia, and the intellectual program that resulted, can also help shed light on more recent trends in organizational studies. © 2001 John Wiley & Sons, Inc.
Male germ cells express abundant endogenous siRNAs

In mammals, endogenous siRNAs (endo-siRNAs) have only been reported in murine oocytes and embryonic stem cells. Here, we show that murine spermatogenic cells express numerous endo-siRNAs, which are likely to be derived from naturally occurring double-stranded RNA (dsRNA) precursors. The biogenesis of these testicular endo-siRNAs is DROSHA independent, but DICER dependent. These male germ cell endo-siRNAs can potentially target hundreds of transcripts or thousands of DNA regions in the genome. Overall, our work has unveiled another hidden layer of regulation imposed by small noncoding RNAs during male germ cell development.
Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer

Abstract Hyperacute rejection of discordant xenografts occurs rapidly, precluding cellular infiltration. Thus the role of cellular rejection in discordant xenografts is debated. Using adoptive transfer of sensitized splenocytes and passive transfer of sensitized serum, we evaluated the influence of cellular and humoral elements on cellular infiltration and rejection in the guinea-pig-to-rat discordant xenograft model. Guinea-pig hearts were transplanted into Lewis rats. Pretransplant, rats underwent splenectomy and plasma exchange and were started on daily cobra venom factor injections. Xenografts rejected faster after adoptive (1, 2, 2 and 2 days) or passive (1, 1, 2 and 2 days) transfer than controls (4, 4, 4 and 4 days; p Our data suggest that either sensitized serum or sensitized cells are capable of initiating an accelerated rejection characterized by cellular infiltration. Despite subtle differences, the population of infiltrating cells was similar in each group. Thus, although rejection may be initiated by either cellular or humoral influences, the ultimate result is the same. We have, therefore, established a small animal model to study cellular rejection in discordant xenografts. This model will help evaluate the role of cell subsets and xenoantibodies in xenograft rejection and will help determine the precise relationship between the two when hyperacute rejection is prevented.
Stress relaxation, internal stress and work hardening in LiF and NaCl crystals

Abstract Stress relaxation is used as an indirect method for determining the velocity-stress exponent for dislocation motion in LiF and NaCl. With the knowledge of this exponent, the applied stress can be separated into its effective stress and internal stress components. The variation of these components with strain is examined and it indicates that work hardening in these crystals is largely due to the development of internal stresses.
Effects of oral estrogen, raloxifene and arzoxifene on gene expression in serotonin neurons of macaques

The serotonin neural system contributes to cognition and affect, both of which exhibit pathologies with gender bias. We previously showed that estrogen (E) treatment of female macaques via Silastic implant alters gene expression for tryptophan hydroxylase (TPH), the serotonin reuptake transporter (SERT) and the 5HT1A autoreceptor. In addition, we have found that serotonin neurons of macaques express ER beta (ERβ). Together these studies suggest that the serotonin neural system could transduce the action of estrogen via ERβ on aspects of mood and cognition. However, estrogen replacement therapy can increase the risk for breast and uterine cancer. Therefore, we questioned whether the selective estrogen receptor modulators, raloxifene and arzoxifene, act in a manner similar to E on gene expression in serotonin neurons of a nonhuman primate model. Female rhesus macaques were ovariectomized and orally dosed with vehicle, estradiol 17β, raloxifene or arzoxifene once per day by sipper bottles for 30 days. The animals were then euthanized and the midbrains were prepared for in situ hybridization for TPH, SERT and 5HT1A receptor mRNAs followed by densitometric analysis. There was a significant increase in TPH total signal (positive pixels×OD) with E, raloxifene and arzoxifene, respectively. There was a significant decrease in SERT mRNA optical density with all treatments. 5HT1A autoreceptor mRNA did not change with any treatment. If these changes in gene expression are reflected by similar changes in the functional proteins, then raloxifene or arzoxifene could increase serotonin neurotransmission with little or no negative action in peripheral tissues. In conclusion, the selective estrogen receptor modulators, raloxifene and arzoxifene, act in a manner similar to natural E on TPH and SERT mRNA expression in serotonin neurons. This suggests that raloxifene and arzoxifene are agonists at ERβ in the context of the serotonin neuron. However, the responses to E were more variable and less robust with the oral dosing paradigm compared to a chronic implant paradigm.
Neighbor-aware dynamic thermal management for multi-core platform

With the high integration density and complexity of the modern multi-core platform, thermal problems become more and more significant for both the manufacture and system designer. Dynamic thermal management technique is one effective and efficient way to mitigate and avoid thermal emergences. In this paper, we propose a novel predictive dynamic thermal management algorithm to maximize the multi-core system throughput while satisfying the peak temperature constraints. Different from the conventional approaches, we found that it is not necessarily always a good choice to migrate a hot task to the core with the lowest temperature. Instead, in our algorithm, we develop a new temperature prediction technique and migration scheme that take the local temperature of a core as well as the impacts from neighboring cores into considerations. According to our experiment results on a practical Intel desktop platform, the proposed algorithm can significantly improve the throughput compared with the conventional approach.
Production of highly polarized vapors using laser optical pumping with velocity-changing collisions

Experiments have shown the novel combination of laser optical pumping and velocity-changing collisions (between active- and buffer-gas atoms) to be very effective in producing vapors with high atomic or nuclear polarizations. This paper presents a theory which has proven successful in analyzing these experiments. The theory predicts the amount of polarization attainable for particular experimental conditions and establishes the general criteria for optimum polarization. The theory is based on sets of coupled rate equations, which contain terms describing the pumping process (i.e., stimulated absorption or emission), radiative branching, relaxation, and velocity-changing collisions. The collision terms are written in the strong-collision approximation, which assumes that a single collision, on average, thermalizes the velocity distribution. Expressions are derived for the polarization and level populations.
Rapid Screening for Temperature-Sensitive Alleles in Plants

We developed a simple and fast method to identify temperature-sensitive alleles of essential plant genes. We used primary and tertiary structure information to identify residues in the core of the protein of interest. These residues were mutated and tested for temperature sensitivity, taking advantage of the exceptionally rapid 1-week complementation assay in the moss Physcomitrella patens. As test molecules, we selected the actin-binding proteins profilin and actin-depolymerizing factor, because they are essential and their loss-of-function phenotype can be fully rescued. Screening a small number of candidate mutants, we successfully identified temperature-sensitive alleles of both profilin and actin-depolymerizing factor. Plants harboring these alleles grew well at the permissive temperature of 20°C to 25°C but showed a complete loss of function at the restrictive temperature of 32°C. Notably, the profilin mutation identified in the moss gene can be transferred to profilins from other plant species, also rendering them temperature sensitive. The ability to routinely generate temperature-sensitive alleles of essential plant proteins provides a powerful tool for the study of gene function in plants.
Landsat-4/5 Band 6 relative radiometry

Relative radiometric responses for the thematic mapper (TM) band 6 data from Landsat-4 and Landsat-5 were analyzed, and an algorithm has been developed that significantly reduces the striping in Band 6 images due to detector mismatch. The TM internal calibration system as originally designed includes a DC restore circuit, which acts as a feedback system designed to keep detector bias at a constant value. There is a strong indication that the DC restore circuitry implemented in Band 6 does not function as it had been designed to. It operates as designed only during a portion of the calibration interval and not at all during acquisition of scene data. This renders the data acquired during the calibration shutter interval period virtually useless for correction of the individual responses of the four detectors in Band 6. It was observed and statistically quantified that the relative response of each of the detectors to the band average is stable over the dynamic range and throughout the lifetime of the instrument. This allows an alternate approach to relative radiometric correction of TM Band 6 images.
A Time-Series Investigation of the U.S. Real Health Expenditure: Evidence from Nonlinear Unit Root Tests

This paper contributes to the literature on health expenditure studies by applying the non-linear unit root tests formulated recently by Kapetanios et al. (Journal of Econometrics 112(2):359–79, 2003) to empirically test whether the U.S. real health expenditure time-series are non-stationary or non-linear and globally stationary during a relatively long period from 1965 to 2009. For comparison purposes, it also reports the results of a battery of traditional linear unit root tests and the Lee and Strazicich’s minimum LM unit root (Review of Economics and Statistics 85(4):1082–1089, 2003) test for structural breaks. The empirical findings of the paper show that in the United States during the period under investigation, the real health expenditure time-series are non-stationary in levels. Policy implications of the empirical findings are discussed.
Surface functionalization for self-referencing surface plasmon resonance (SPR) biosensors by multi-step self-assembly

Abstract Recently, a novel SPR sensor with on-chip referencing has been realized. In this sensor, one-half of the gold sensing surface is covered with a high refractive index overlayer of tantalum pentoxide (Ta2O5). When polychromatic beam illuminates the sensing surface, surface plasmon resonance in the areas with and without the overlayer occur at different wavelengths. Therefore, the reflected light exhibits two dips associated with SPRs in those two areas. When functionalized properly, one of the areas can be used as a specific sensing channel for detection of specific bio-interactions and the other can act as a reference channel for compensation for background refractive index fluctuations. In this paper we present a new functionalization approach for these mixed architecture chips. The gold side of the chip is functionalized with a mixed self-assembled monolayer of polyethylene oxide (PEO) and biotin terminated (BAT) thiols whereas the Ta2O5 side is coated with PEO terminated silanes. The PEO terminated thiols and silanes serve as a protein resistant background, while the biotin terminated thiols are used to bind streptavidin, which in turn immobilizes biotinylated antibodies. Hence, the gold side of the chip is used for the binding and detection of target analytes and the Ta2O5 side functions as a reference channel that monitors bulk refractive index changes and temperature drift. We have studied human chorionic gonadotropin (hCG) as a model system, currently detecting down to 5 ng/ml. In addition, we demonstrate the power of the on-chip reference channel for compensating for refractive index changes and eliminating false alarms.
Effects of cholinesterase inhibitors on the neuromuscular blocking action of suxamethonium.

Prolonged neuromuscular block occurs when suxamethonium is given after neostigmine or pyridostigmine; however, studies of edrophonium and suxamethonium have yielded conflicting results. We have studied, therefore, interactions between suxamethonium and all three anticholinesterases in rats anaesthetized with pentobarbitone. After recovery from an initial bolus of suxamethonium, saline, edrophonium, pyridostigmine or neostigmine was administered and a second dose of suxamethonium was then given. All three anticholinesterases prolonged the duration of neuromuscular block (90% suppression to 50% twitch recovery) to 127(SEM 9)%, 127(10)% and 138 (11)% of baseline for edrophonium, pyridostigmine and neostigmine, respectively. Recovery index (25% to 75% twitch recovery) was increased also to 125 (9)%; 149 (10%) and 185 (15)% of baseline, respectively for the three drugs.
Abstract 3064: An alternative mechanism of action for paclitaxel in breast cancer

Paclitaxel is a microtubule-stabilizing drug that binds to the β-tubulin subunit and accumulates in mitotic cells. As a chemotherapeutic agent, paclitaxel is used for the treatment of a variety of cancers including breast. Currently, no biomarker is available to predict which patients will benefit from paclitaxel treatment. Paclitaxel studies in cells focus primarily on relatively high concentrations of the drug, which cause cells to die following long-term mitotic arrest. The clinically relevant concentration of paclitaxel is currently unknown, although it is widely speculated to be in the low nM range. Cells exposed to low concentrations of paclitaxel complete mitosis with minimal delay, but frequently contain multipolar spindles. In chromosomally stable breast cancer cells, low concentrations of paclitaxel are sufficient to increase aneuploidy within two days of exposure. These data suggest that the mechanism of cell death due to low dose paclitaxel is likely to be quite different from the mechanism of cell death caused by high dose paclitaxel. They also predict that chromosomally instable (CIN) cells may be more sensitive to cell death caused by low doses of paclitaxel. CIN cells have an existing level of chromosomal missegregation, which is likely to be exacerbated by treatment with low doses of paclitaxel. Since missegregation of large numbers of chromosomes per division causes rapid cell death, these cells may be more likely to die after low dose paclitaxel treatment as a result of losing both copies of a vital chromosome. Chromosomally stable cells, which do not normally missegregate chromosomes with each division, would be more resistant to death following paclitaxel treatment than CIN cells. These data suggest that CIN may be used as a biomarker to determine which tumors are most likely to be sensitive to treatment with clinically relevant concentrations of paclitaxel. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3064. doi:1538-7445.AM2012-3064
Solar Cycle Variations in the Composition of the Suprathermal Heavy-Ion Population near 1 AU

We have measured the annual variation in the quiet-time composition of interplanetary suprathermal ions between 0.04 and 1 MeV nucleon-1 from 1994 November 20 through 2006 January 1. Our results show the following: (1) The C/O and Fe/O ratios are similar to the corresponding values measured in the solar wind and corotating interaction regions (CIRs) during solar minimum conditions of 1994-1997 and 2005. (2) During periods of increased solar activity between 1998 and 2002, the C/O ratio is similar to that measured in solar energetic particle (SEP) events, while the Fe/O ratio lies between the values measured in coronal mass ejection-driven interplanetary shock and SEP events. (3) The 3He/4He ratio lies in the 1.5%-5% range during 1997-2005 August, but it dropped by an order of magnitude during 2005. We conclude that the composition of the suprathermal ion population between ~6 and 30 times the solar wind speed near 1 AU is dynamic and is essentially dominated by ions accelerated in SEP events during solar maximum conditions and by suprathermal solar wind ions and/or those accelerated in CIRs during solar minimum conditions.
Group Identification and Group Homogeneity: A Case Study of NOLS Courses

Group processes are a central aspect of all outdoor adventure education (OAE) programs. How well a group functions is a product of the interactions between individuals and can have an impact on the individual and group outcomes of the program. Group identification shows how members identify with individuals in the group and the group as a whole (Henry, Arrow, & Carini, 1999). By increasing the individual level of group identity, groups can become more efficient and work harder toward the group's goal (Haslam, 2004). When members of the group have higher levels of identity, they see their own values and interests coming together with that of the group, thus â€œanchoringâ€ them closer and stronger to the group (Anderson, Riddle, & Martin, 1999; Cassidy, 2007). Thus, group identification is a construct that can provide a sense of how well a group functions.
Rousseau and the tensions of France's Contrat d'Accueil et d'Intégration

The Contrat d'Accueil et d'Integration is the keystone of France's revamped immigration paradigm aimed at integrating immigrants into French society and fostering social cohesion through adherence to a Rousseauian social contract. Because the use of the social contract as an immigration tool taps into an ideal (and thus flawed) philosophical tradition, it is important to move beyond the procedural mechanism and political implications to probe the deeper philosophical issues raised by grafting a Rousseauian social contract onto the immigration realm. From a Rousseauian perspective, discerning the nature of French republicanism is not a question of which paradigm—the traditional republican or the multicultural—has the better understanding of the fundamental values of modernity. Rather, what matters is how the French public views the scope of these values and whether the laws promulgated by the government in power reflect the general will of society as a whole. The contribution of this article lies in exposi...
The Isolation and Fractionation of Chicken Egg White Ovomucin

Abstract Three fractions of chicken egg white ovomucin were obtained from ovomucin precipitated by the classical method of dilution of egg white with water. The first fraction was obtained by dilute salt extraction of the precipitated ovomucin and consisted of smaller components of ovomucin. The second fraction was obtained by extraction with 1 M KCl of the precipitate remaining after dilute salt extraction and consisted of a heterogeneous mixture of components of larger mass. The third fraction, the ovomucin remaining after concentrated salt extraction, was insoluble. The two soluble fractions were found to be unstable with time (pH 8, μ 0.2). The rate of breakdown was slower in concentrated salt solution. The final breakdown product(s) for both fractions appeared to be a 6 S component (s) of molecular mass 1.5 × 105 daltons.
An optimization model and multiple matching heuristics for quality planning in manufacturing systems

Planning quality control operations for parts assigned to a manufacturing system is an important decision-making process. It involves the selection of quality tools and assignment of the tools and quality operations to machine centers or inspection stations. The problem is complicated by multiple variables involved and the interactions between the variables. Trade-off must be made to minimize the total cost and satisfy demands and resource constraints. Mathematical formulation can be used to integrate the decisions and characterize the problem. More efficient heuristic algorithms are developed based on a tripartite graph representation of the original problem. Experimental results showed that the algorithms proposed are effective and efficient in their computational performance.
A comparison of eluting agents for the ion-exchange purification of promethium

Abstract Laboratory experiments have shown that NTA (nitrilotriacetic acid) is markedly superior to EDTA (ethylenediaminetetraacetic acid) or DTPA (diethylenetriaminepentaacetic acid), the complexing agents previously used, for kilogram-scale ion-exchange purification of promethium. With NTA elution at 60°C, the position of yttrium is changed from the critical SmPmNz zone (with DTPA the sequence is SmYPm) to a place ahead of gadolinium; yielding an elution order: Y, Gd, Eu, Em, Pm, Nd, Pr. As a result of faster kinetics in the NTA system, a 100 per cent increase in the rate of band advance, compared to the rate obtained in the previously used DPTA process, can be achieved with equal or superior separation efficiency. The time required for a 300,000 Ci purification run has been reduced from 21 days with EDTA or 6 days with DTPA to less than 3 days with NTA.
Interfaces and fatigue Damage in a Ti-15-3/SCS-6 [0/90]2s Composite

The key role of interfaces in the initiation and propagation of fatigue damage is elucidated for a model eight ply [0/90] 2s Ti-15V-3Cr-3Al-3Sn (Ti-15–3) composite reinforced with SiC (SCS-6) fibers. Interfacial strengths obtained from fiber push-out tests are used in the quantification of shielding due to crack bridging. Composite fatigue tests are predicted using an idealized fracture mechanics model. The possible effects of interfacial strength variation on the predicted fatigue lives are also elucidated.
Regulation of Nitric Oxide Production by Tetrahydrobiopterin

The discovery of endothelium-derived relaxing factor (EDRF) by Furchgott and Zawadzki1 in 1980 and its identification as nitric oxide (NO) by Palmer and coworkers2 were key observations for our understanding of the physiology of vasodilation. Recently, the realization that tetrahydrobiopterin (BH4) may regulate the availability of EDRF has given us further insights into the regulation of vascular tone and refocused attention on the complex chemistry associated with NO synthase (EC 1.14.13.39) catalysis.3 4 NO synthases belong to large family of closely related enzymes that utilize a number of cofactors, including BH4, for production of NO from l-arginine. In the absence of BH4, NO synthases no longer produce NO but can catalyze reactions leading to the production of hydrogen peroxide (H2O2). In certain blood vessels, H2O2 mediates relaxation, and this may compensate for the loss of NO production due to the absence of BH4. Observations to support this have been made by Cosentino and Katusic5 using isolated rings of canine coronary arteries and 2,4,-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 synthesis. The importance of NO for many physiological pathways and its ubiquitous distribution throughout the body led to its nomination as the molecule of the year in 1992.6 An extensive family of NO synthases has been identified, and they can be subdivided into isoforms that are expressed constitutively and those that are evident only after induction. Production of NO by the latter group is often associated with cytotoxicity, and this is due in part to the very large quantities synthesized by the inducible enzyme systems.7 Both enzyme types have been cloned from a number of species and tissues, and they share common features related to the reactions they catalyze with l-arginine (see References 4 and 7 for reviews). …
Synthesis and Evaluation of Diphenyl Phosphonate Esters as Inhibitors of the Trypsin-like Granzymes A and K and Mast Cell Tryptase

Thirty-six new amino acid and peptidyl diphenyl phosphonate esters were synthesized and evaluated to identify potent and selective inhibitors for four trypsin-like proteases: lymphocyte granzymes A and K, human mast cell tryptase, and pancreatic trypsin. Among five Cbz derivatives of Lys and Arg homologues, Z-(4-AmPhe)P(OPh)2 is the most potent inhibitor for granzyme A, and Z-LysP(OPh)2 is the best inhibitor for granzyme K, mast tryptase, and trypsin. The amidino P1 residue D,L-(4-AmPhGly)P(OPh)2 was utilized in a series of compounds with several different N-protecting groups and systematic substitutions at P2 in Cbz-AA derivatives and at P3 in Cbz-AA-Ala derivatives. Generally, these phosphonates inhibit granzyme A and trypsin more potently than granzyme K and tryptase. The P2 Thr and Ala dipeptide phosphonates, Cbz-AA-(4-AmPhGly)P(OPh)2, are the most potent inhibitors for granzyme A, and Cbz-Thr-(4-AmPhGly)P(OPh)2 (kobs/[I] = 2220 M-1 s-1) was quite specific with much lower inhibition rates for granzyme K and trypsin (kobs/[I] = 3 and 97 M-1 s-1, respectively) and no inhibition with tryptase. The most effective inhibitor of granzyme A was Ph-SO2-Gly-Pro-(4-AmPhGly)P(OPh)2 with a second-order rate constant of 3650 M-1 s-1. The most potent inhibitor for granzyme K was 3, 3-diphenylpropanoyl-Pro-(4-AmPhGly)P(OPh)2 with a kobs/[I] = 1830 M-1 s-1; all other phosphonates inhibited granzyme K weakly (kobs/[I] < 60 M-1 s-1). Human mast cell tryptase was inhibited slowly by these phosphonates with Cbz-LysP(OPh)2 as the best inhibitor (kobs/[I] = 89 M-1 s-1). The overall results suggest that scaffolds of Phe-Thr-(4-AmPhe) and Phe-Pro-Lys will be useful to create selective phosphonate inhibitors for granzymes A and K, respectively, and that P4 substituents offer opportunities to further enhance selectivity and reactivity.
Hydrolysis of Secreted Sialoglycoprotein Immunoglobulin A (IgA) in ex Vivo and Biochemical Models of Bacterial Vaginosis

Bacterial vaginosis (BV) is a common polymicrobial imbalance of the vaginal flora associated with a wide variety of obstetric and gynecologic complications including serious infections and preterm birth. As evidenced by high recurrence rates following treatment, interventions for BV are still lacking. Several hydrolytic activities, including glycosidases and proteases, have been previously correlated with BV and have been hypothesized to degrade host sialoglycoproteins that participate in mucosal immune functions. Sialidase activity is most predictive of BV status and correlates strongly with adverse health outcomes. Here we combine clinical specimens with biochemical approaches to investigate secretory immunoglobulin A (SIgA) as a substrate of BV-associated glycosidases and proteases. We show that BV clinical specimens hydrolyze sialic acid from SIgA, but not in the presence of the sialidase inhibitor dehydro-deoxy-sialic acid. The collective action of BV-associated glycosidases exposes underlying mannose residues of SIgA, most apparent on the heavily N-glycosylated secretory component of the antibody. Terminal sialic acid residues on SIgA protect underlying carbohydrate residues from exposure and hydrolysis by exoglycosidases (galactosidase and hexosaminidase). It is known that both IgG and SIgA are present in the human reproductive tract. We show that the IgG heavy chain is more susceptible to proteolysis than its IgA counterpart. Gentle partial deglycosylation of the SIgA secretory component enhanced susceptibility to proteolysis. Together, these data support a model of BV in which SIgA is subject to stepwise exodeglycosylation and enhanced proteolysis, likely compromising the ability of the reproductive mucosa to neutralize and eliminate pathogens.
High Efficiency WCDMA Power Amplifier With Pulsed Load Modulation (PLM)

Complex non-constant-envelope modulations are often used in wireless communications. A power amplifier (PA) is developed based on the concept of pulsed load modulation (PLM) that can enhance the power efficiency of the PA when the output power is back off from the peak due to modulations. The PLM technique utilizes the time-varying behavior of switched resonators to form an optimal, power dependent load impedance. The switched resonator consists of a balanced pair of switching mode PAs that drive a high-Q bandpass filter. In addition to its efficiency enhancement through PLM, the PA is able to preserve the linearity of complex modulations through the architecture of envelope delta-sigma modulation (EDSM). In this paper, a 1.87 GHz PLM power amplifier is fabricated with a pair of 0.35 μm GaAs pHEMT devices. The duty cycle tests show its significant improvement on power efficiency at different back-off levels over traditional Class-B amplifiers. The PA module is also tested with a single-channel WCDMA signal with peak to average ratio (PAR) of 10.8 dB. It has achieved 39 dBc adjacent channel leakage ratio (ACLR) at 5 MHz offsets without needing additional linearization techniques. The power added efficiency in this case is 43% including the loss of the output filter and 52.6% if the loss of the filter is de-embedded.
Life Stressors as Risk Factors in Depression

Compelling evidence for an association between major adverse life experience and subsequent major depression is reviewed. Determining individual vulnerability to life stress and the effect of stressors on treatment outcome of depression are highlighted as the next major targets for contemporary stress research. Methodological concerns in the evaluation of stressors are detailed, and available data on variables that may influence the stress-depression relationship are presented. The critical importance of multivariate models in understanding individual vulnerability and outcome is emphasized. As methods for ascertaining stressful life events and chronic stressors continue to be refined, and models addressing the complex relationship of stressors and depression continue to be developed, prediction of stressor effects in onset and outcome of major depression will become increasingly more precise.
An Algorithm for Volume Estimation Based on Polyhedral Approxi mation

A volume algorithm is established which uses the data generated by computed tomography (CT) or ultrasound scans. The algorithm is based on a polyhedral reconstruction of an object of interest. Phantom studies indicate that the algorithm calculated volume is accurate within 3 percent. In a controlled clinical experiment on a laboratory animal, the algorithm calculated volume showed a maximum error of about 5 percent. In less controllable applications to human clinical data, volume calculations showed variations ranging up to 16 percent.
Mechanics of mixed mode small fatigue crack growth

Abstract An elastic-plastic analysis of a mixed mode crack was conducted under general yielding conditions using a finite element method. Based on the finite element analysis, a formula of the J-integral was developed, and the behavior of the crack opening or sliding displacement was investigated. Crack growth mechanics was discussed to explain mixed mode growth. A model expressed by the J-integral was proposed assuming that the crack growth is determined by the linear summation of relations of pure Mode I and II crack-tip deformation. The crack growth rate obtained using Inconel 718 thin-wall tubular specimens was correlated with the range of ΔJ evaluated from the proposed formula. The crack growth equations in terms of ΔJ for three different biaxial strain ratios were compared with the relations expected from the proposed crack growth model. The difference between the experimental results and the estimation was discussed from the viewpoint of crack closure and the geometry of the surface crack.
Particle flow inspired by Knothe-Rosenblatt transport for nonlinear filters

We derive a new algorithm for particle flow corresponding to Bayes’ rule that was inspired by Knothe- Rosenblatt transport, which is well known in transport theory. We emphasize that our flow is not Knothe- Rosenblatt transport, but rather it is a completely different algorithm for particle flow. In particular, we pick a nearly upper triangular Jacobian matrix, but the meaning of the word “Jacobian” as used here is completely different than used in Knothe-Rosenblatt transport.
An implementation of collaborative adaptation of cognitive radio parameters using an ontology and policy based approach

The main objective of this paper is to demonstrate the feasibility of the ontology and policy based approach to realize collaborative, automatic adaptation of cognitive radio parameters in the transmitter and receiver. The ontology and policy based approach features the following three aspects. First, all the internal and external information of the radio is represented in the Web Ontology Language (OWL). The transmitter and receiver share the same core ontology and thus can communicate with each other using this common language. Second, the policy rules are written in a declarative form and interpreted by a reasoner. Third, in order to exchange the OWL represented information between the radios, we adopt a more flexible signaling plan, which is different than the conventional protocol-predefined signaling plan, i.e. the control messages are added to an extendable payload, rather than embedded in the predefined protocol-dependent header or trailer. The paper discusses the implementation and shows some examples of radio behaviors resulting from the execution of the policies.
Chemoradiation-induced cell loss in human submandibular glands.

Objectives: Chemoradiation-induced xerostomia affects approximately 40,000 head and neck cancer patients annually in the United States. No human histopathologic or immunohistochemical data exist that characterize chemoradiation-related salivary gland damage. The objective of this study was to describe the histopathologic and immunohistochemical features of the non-acute phase of human submandibular gland damage after chemoradiation therapy. Methods: Pathologic materials were retrieved from patients who had undergone neck dissection after protocol-driven chemoradiotherapy for stage IV head and neck cancer at a tertiary head and neck cancer institute. Histologic and immunohistochemical analyses were performed on representative sections of chemoradiated submandibular glands, and findings were compared to age- and sex-matched, untreated control glands. Results: Forty patients were identified who had undergone neck dissection an average of 11 weeks after treatment with induction chemotherapy and chemoradiation therapy for non-oral head and neck cancer. In the chemoradiated glands, light microscopic findings included pronounced acinar cell loss with accompanying ductal metaplasia and ductal proliferation and increased fibrosis, chronic inflammation, nuclear atypia, and cytoplasmic vacuolization when compared with controls. Microvascular density was marginally affected by chemoradiation; cytokeratin staining showed preservation of ductal epithelium when compared to controls. Conclusions: Nonacute changes seen in human submandibular glands after chemoradiation therapy are compared to those seen in previously described irradiated animal and human models. Primary dysfunction in humans appears to be related to a reduction in function and number of submandibular gland acinar cells. The ductal system appears to be preserved after chemoradiation therapy. Implications for management of xerostomia are discussed. Key Words: Chemoradiation, xerostomia, submandibular gland. Laryngoscope, 115:958–964, 2005
Function allocation: algorithm, alchemy or apostasy?

Abstract Fitts gave us our list, the function allocation counterpart of Moses' 10 commandments, or Luther's 95 theses. Based on the qualitative axioms of Fitts, we have sought to evolve function allocation into a science. But can usable algorithms or procedures be attained? Thus far the logic has eluded us, in spite of valiant efforts. Some have declared in disgust that function allocation can never be more than black art. Must we admit that function allocation is mostly art, judgement based on experience, with little prospect for rigorous science? Or in the end must we become apostates, and abandon our hopes for rational function allocation according to those scientific principles we have held so dear in practicing our profession? The paper discusses the following problems of function allocation: (1) computers, automation and robotics offer ever greater capability, but at the cost of greater system complexity and designer bewilderment, making the stakes for function allocation ever higher than before; (2) proper function allocation differs by process stage; (3) automation appears most promising at intermediate complexity, but the bounds of “intermediate” are undefined; (4) “human-centered design”, while an appealing slogan, is fraught with inconsistencies in definition and generalizability; (5) “naturalistic decision-making” and “ecological” design are incompatible with normative decision theory; (6) function allocation is design, and therefore extends beyond science; and (7) living with the technological imperative, letting our evolving machines show us what they can do, acceding or resisting as the evidence becomes clear, appears inevitable. In spite of our best efforts to cope with these and other problems of function allocation, error and dispute over allocation criteria are human nature. Perhaps that is part of the Darwinian reality, the requisite variety, the progenitor of progress. At least we have it in our power to say no to new technology, or do we?
How Does the Perception of a Lesion Influence Visual Search Strategy in Mammogram Reading

Rationale and Objectives Radiologists do not decide whether to report or to dismiss a perceived finding based solely on the conspicuity of the finding itself, but rather, they compare the finding with selected areas of the background. In this article, we examined how the perception of a malignant mass changed the background sampling strategy of experienced mammographers when searching mammograms for breast cancer. We determined whether these changes were different for correctly reported masses and for both visually inspected but unreported masses (ie, misses) and for lesion-free areas that were interpreted as containing a malignant mass (ie, false-positive decisions). Materials and Methods Four experienced mammographers read a case set of 20 two-view mammograms on two trials. Fifteen cases contained one biopsy-proven malignant mass, and five cases were lesion-free. Each cancer case had two sets of images: 1) the ones in which the lesion was reported at mammography screening, and 2) the first prior mammogram. On each trial, for each cancer case, only one set of images was shown to the observer in a balanced mix of current and prior cases per trial. The complementary set was shown in the next trial. The lesion-free cases were shown in both trials. The observers’ eye positions were recorded. Spatial frequency analysis was used to represent the observers’ background sampling strategy, and analysis of variance and correlation analysis were used to evaluate whether there were significant differences in the background areas sampled before and after the observers’ eyes hit for the first time the location of the lesion. Results We found statistically significant differences (analysis of variance F(1,19) = 12.812, P = .0003) in the spatial frequency representation of the background areas sampled before and after the observers’ eyes first hit the location of a true malignant mass. There were no statistically significant differences in the spatial frequency representation of background areas sampled before and after the observers’ eyes first hit the location of a correctly reported malignant mass, but there were significant differences when either the observer did not report the mass (a miss) or the observer reported a lesion-free area as containing a mass (a false positive). Conclusion A true malignant mass that the observers correctly report may be perceived immediately after image onset, thus biasing background sampling from the start, whereas areas that yield both false-negative and false-positive decisions may only be perceived during visual examination of the parenchyma. For the false negatives, our data suggest that after fixating the location of the lesion, the observers actively tried to reconcile the perception of the lesion with its background, whereas for the false positives, which represent a “true” lesion for the observers, background sampling was clearly different before and after the location was fixated for the first time. Hence, the perception of a finding effectively biases any further analysis of the case.