cssi/SciSciGPT-SciSciNet huggingface dataset:
Retinal ganglion cell response to axotomy in the regenerating visual system of the newt (Triturus viridescens): an ultrastructural morphometric analysis.

Abstract The neuronal perikaryal response to axotomy in the retinal ganglion cell layer of the newt ( Triturus viridescens ) is a rapid and dramatic phenomenon. The earliest morphological changes are found in the nucleus and are prominent by 4 to 7 days postaxotomy (DPA). At that time, axotomized neurons begin to exhibit a dramatic chromatin pattern change from a heterochromatic to a euchromatic state. In addition, large multiple nucleoli are often seen in reactive nuclei, where one small nucleolus may infrequently be found in nuclei of intact controls. The passage of the ganglion cells through the various stages of nuclear reactivity can be plotted temporally. By 14 DPA the number of retinal ganglion cells demonstrating reactive nuclei and prominent nucleoli has reached a peak which continues through 21 DPA but thereafter declines returning to control conditions by 90 DPA. Only 50% to 60% of neurons within the retinal ganglion layer enter the reactive nuclear stages in response to axotomy. Therefore, a clear distinction can be made at the light microscopic level between reactive and nonreactive neurons with respect to changes in nuclear morphology. Neuronal perikaryal changes appearing later in response to axotomy can be demonstrated by electron microscopic morphometric analysis. By 7 DPA the only quantitatably significant changes are increases in the number and size of nucleoli per cell. However, by 14 DPA reative neurons show significant nuclear and cytoplasmic hypertrophy compared to intact controls and 7-DPA animals. In addition, significant increases in numbers of mitochondria, Golgi fields, and nucleoli were quantitated. Increases in bound and unbound ribosomes and nerotubules were also observed by 14 DPA.
Characteristics of 16-dehydroprogesterone reductase in cell extracts of the intestinal anaerobe, Eubacterium sp. strain 144.

Abstract 16-Dehydroprogesterone reductase (16-DHPR) activity was present in cell extracts of Eubacterium sp. strain 144 only when the organism was grown in the presence of steroids containing a Δ 16–17 double bond and C-20-ketone. Cells grown with 16-dehydropregnenolone contained 16-DHPR activity but lacked Δ 4–5 -3-keto steroid reductase activity. Pyruvate or sodium dithionite served as electron donors for 16-DHPR and both reactions required methyl viologen as an electron carrier. Neither NADH nor NADPH, with or without flavin nucleotides, were used by 16-DHPR. Enzyme activity was detected in the cytoplasmic fraction (40%) and membrane fraction (20%) of crude cell extracts, but 40% of the activity was unaccounted for following ultracentrifugation. 16-DHPR activity was unaffected by pH in potassium phosphate buffer over the range 5.0 to 8.5, but was inhibited by Tris-HCl above pH 7.0. 16-DHPR activity was inhibited by sulfhydryl reagents, but inhibitors of electron transport reactions or metal chelators did not affect the enzyme.
Adaptive system stability robustness via burst recovery

Abstract Adaptive systems which are based on a posteriori parameter update algorithms are shown to possess a specific type of ‘self-stabilization’ property, termed burst recovery. This results in bounded-disturbance bounded-error stability, provided that unbounded parameter drift does not occur. Persistent excitation prevents unbounded parameter drift, but only when both upper and lower bounds on excitation exist. For many adaptive systems, an upper bound on excitation cannot be assured using standard perturbation analyses, which require the disturbance to be ‘suitably small’ compared to the lower bound on excitation. This paper proves that burst recovery in conjunction with only a lower bound on excitation provides bounded-disturbance bounded-error stability. The disturbance need not be small, and additional algorithm modifications (such as parameter projection) are not necessary.
Random changepoint modelling of HIV immunologic responses

We propose a changepoint model for the analysis of longitudinal CD4 T-cell counts for HIV infected subjects following highly active antiretroviral treatment. The profile of CD4 counts for each subject follows a simple, 'broken stick' changepoint model, with random subject-specific parameters, including the changepoint. The model accounts for baseline covariates. The longitudinal CD4 records are censored at the time of the subject going off-study-treatment. This is a potentially informative drop-out mechanism, which we address by modelling it jointly with the CD4 count outcome. The drop-out model incorporates terms from the CD4 model, including the changepoint. The estimation is done in a Bayesian framework, with implementation via Markov chain Monte Carlo methods in the WinBUGS software. Model selection using DIC indicates that the data support the complex random changepoint and informative censoring model.
Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with Klebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice. Male and female C57BL/6 mice were exposed to O3 or to filtered air (FA) (control) and then infected intratracheally with K. pneumoniae bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h. 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice. O3 exposure reduces the ability of mice to survive K. pneumoniae infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.
Aspirin increases tissue oedema after skeletal muscle ischaemia and reperfusion

Purpose : Skeletal muscle ischaemia reperfusion syndrome affects patients following lower limb revascularisation. Aspirin has the potential to attenuate these effects. Methods : Using an established model of hind limb tourniquet ischaemia, the effects of oral and intravenous aspirin administration were observed after 6 h of ischaemia and 18 h reperfusion. Samples were obtained and analysed for muscle viability and oedema, and lung neutrophil infiltration. Results : Aspirin, when compared to placebo and controls, significantly increased muscle interstitial oedema when given orally and intravenously. It had no effect on tissue viability or lung neutrophil infiltration. Conclusion : Aspirin increases tissue oedema after ischaemia and reperfusion but has no effect on tissue viability. Although its mechanism of action has not been clarified, aspirin may influence the no-reflow component of ischaemia-reperfusion syndrome.
High power microwave slow wave structure for relativistic beams

High power RF sources are used in many applications including Satellite communications, Radar, Electronic Counter-Measures (ECM). Most of them consist of Klystrons, Magnetrons or Gyrotrons which are narrow band, bulky structures. Very few TWTs compatible with very high power (above 100KW) in S-band have been reported in literature. A challenge in designing small, high power TWTs relates to over-heating that counter the principles for designing slow-wave structures. Other difficulties lie in the formulating very high beam velocity using very small electrical lengths. More specifically, small electrical lengths do not interact efficiently with the incoming electron beam. Also, for large phase velocity waves, the interaction impedance decreases, causing lower gain and output power. With these challenges in mind, and with goal of reducing the size of TWTs, in this paper we investigate (1) novel slow-wave structures to achieve large RF phase velocity with moderate interaction impedance, (2) materials for structural stability to counter heating effects.
A case study on how to manage the theft of information

This paper shows the importance that management plays in the protection of information and in the planning to handle a security breach when a theft of information happens. Recent thefts of information that have hit major companies have caused concern. These thefts were caused by companies' inability to determine risks associated with the protection of their data and these companies lack of planning to properly manage a security breach when it occurs. It is becoming necessary, if not mandatory, for organizations to perform ongoing risk analysis to protect their systems. Organizations need to realize that the theft of information is a management issue as well as a technology one, and that these recent security breaches were mainly caused by business decisions by management and not a lack of technology.
Tracing requirements to defect reports: an application of information retrieval techniques

To support debugging, maintenance, verification and validation (V&V) and/or independent V&V (IV&V), it is necessary to understand the relationship between defect reports and their related artifacts. For example, one cannot correct a code-related defect report without being able to find the code that is affected. Information retrieval (IR) techniques have been used effectively to trace textual artifacts to each other. This has generally been applied to the problem of dynamically generating a trace between artifacts in the software document hierarchy after the fact (after development has proceeded to at least the next lifecycle phase). The same techniques can also be used to trace textual artifacts of the software engineering lifecycle to defect reports. We have applied the term frequency–inverse document frequency (TF-IDF) technique with relevance feedback, as implemented in our requirements tracing on-target (RETRO) tool, to the problem of tracing textual requirement elements to related textual defect reports. We have evaluated the technique using a dataset for a NASA scientific instrument. We found that recall of over 85% and precision of 69%, and recall of 70% and precision of 99% could be achieved, respectively, on two subsets of the dataset.
An objective kinematical formalism for the modeling of elastic-plastic materials subject to large deformation

A kinematical formalism for the analysis of two superposed finite elastic-plastic deformations is presented. This is offered as an alternative to the unnecessarily complex (in the view of this author) kinematical development of Schieck and Stumpf in the accompanying Journal article entitled “Deformation Analysis for Finite Elastic-Plastic Strains in a Lagrangean-Type Description” (Schieck and Stumpf, 1993, Int. J. Solids Structures30). It is claimed that this provides an equivalent kinematical foundation for their principal results.
Measurements of aerosol size‐resolved hygroscopicity at sub and supermicron sizes

[1] Airborne measurements of size-resolved aerosol hygroscopicity are presented using an optical particle counting and sizing technique. The measurement range of 0.25 to 3.5 μm is significantly greater, and extends to larger sizes, than previous in situ techniques. Preliminary results reveal a peak in aerosol hygroscopicity in the 0.5 –1.5 μm diameter size range in both marine and polluted aerosols. Geometric growth factors range from 1.3 to 1.5 and 1.1 to 1.3 for the sub and super-micron particles, respectively.
Efficient reachability checking using sequential SAT

Reachability checking and preimage computation are fundamental problems in ATPG and formal verification. Traditional sequential search techniques based on ATPG/SAT, or on OBDDS have diverging strengths and weaknesses. Here, we describe how structural analysis and conflict-based learning are combined in order to improve the efficiency of sequential search. We use conflict-based learning and illegal state learning across time-frames. We also address issues in efficiently bounding the search space in a single time-frame and across time-frames. We analyze each of these techniques experimentally and demonstrate the advantages of each technique. We compare performance against a commercial sequential ATPG engine and VIS [RK. Brayton et al., (1996)] on a set of standard benchmarks.
Methodology for cell transformation assays with C3H/10T1/2 mouse embryo fibroblasts

Basic cell culture conditions required for execution of cell transformation studies with C3H/10T1/2 mouse embryo fibroblasts are described. These protocols permit assessment of the ability of chemicals to convert nontumorigenic C3H/10T1/2 cells to a tumorigenic phenotype characterized by altered controls upon in vitro cell division. Recent assay modifications that enhance the sensitivity of this focus formation assay and permit the study of multistage transformation processes are noted.
Three-dimensional reversed horseshoe vortex structures under broken solitary waves

Abstract Turbulent vortical structures under broken solitary waves are studied using three-dimensional smoothed particle hydrodynamics (SPH) method. The numerical model predicts water surface evolution and horizontal velocity very well in comparison with the experimental results. The numerical results detect organized coherent structures characterized as reversed horseshoe (hairpin) vortices being generated at the back of the broken spilling wave and traveling downward. The counter rotating legs of the reversed horseshoe structures appear to be a continuous form of the previously found obliquely descending eddies. The reversed horseshoe structures are associated with the turbulence motion of sweep events (downwelling motion) and transport momentum and turbulent kinetic energy downward into the water column. Vortex turning play an important role on the generation and evolution of three dimensional reversed horseshoe structures from the spanwise breaking wave rollers.
Basal and reactive plasma catecholamine levels under stress and anesthesia in rabbits.

Abstract The present study was undertaken to determine if electrical stimulation of the hypothalamic defense area (HDA) and baroreflex activation elicited by head up body tilt produced changes in plasma catecholamine (CA) levels in anesthetized rabbits. We also compared the effects of two anesthetics, isoflurane and sodium pentobarbital, upon basal and reactive CA levels, and upon autonomic reactivity. HDA stimulation was found to produce significant increases in plasma norepinephrine (NE) levels but not epinephrine (E) levels. Passive tilt was found to produce statistically significant increases in NE levels for both anesthetics used and a significant increase in E levels for animals anesthetized with isoflurane. Basal and reactive measurements provided evidence that pentobarbital has a more suppressive effect upon the autonomic nervous system than isoflurane: (a) Basal NE levels were significantly lower in pentobarbital-anesthetized animals than in isoflurane-anesthetized animals; and (b) Baroreceptor sensitivity to a passive tilt stressor was significantly higher for animals anesthetized with isoflurane than for animals anesthetized with pentobarbital.
Time reversal communication with a mobile source

Broadband underwater acoustic communication signals undergo either a compression or dilation in the presence of relative motion between a source and a receiver. Consequently, underwater acoustic communications with a mobile source/receiver require Doppler compensation through resampling. However, resampling may not be necessary when a channel-estimate-based time reversal approach is applied with frequent channel updates. Using experimental data (20–30 kHz), it is demonstrated that the performance of time reversal communication without resampling is similar to the case with resampling, along with the benefit of a modest computational saving.
4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2Y6 receptor

4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y6R potency generally better than γ-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y6R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y6R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t1/2 of 18 min) and surface-bound fluorescence. Known P2Y6R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y6R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y6R.
Total internal reflection photoacoustic spectroscopy for the detection of β-hematin.

Evanescent field sensing methods are currently used to detect many different types of disease markers and biologically important chemicals such as the HER2 breast cancer receptor. Hinoue et al. used Total Internal Reflection Photoacoustic Spectroscopy (TIRPAS) as a method of using the evanescent field to detect an optically opaque dye at a sample interface. Although their methods were successful at detecting dyes, the results at that time did not show a very practical spectroscopic technique, which was due to the less than typical sensitivity of TIRPAS as a spectroscopy modality given the low power ( ∼ 1 to 2 W) lasers being used. Contrarily, we have used an Nd:YAG laser with a five nanosecond pulse that gives peak power of 1 MW coupled with the TIRPAS system to increase the sensitivity of this technique for biological material sensing. All efforts were focused on the eventual detection of the optically absorbing material, hemozoin, which is created as a byproduct of a malarial infection in blood. We used an optically analogous material, β-hematin, to determine the potential for detection in the TIRPAS system. In addition, four properties which control the sensitivity were investigated to increase understanding about the sensor's function as a biosensing method.
The crystal structure of trifluoromethylcobalamin, a coenzyme B12 analog

Abstract The X-ray crystal structure of β-trifluoromethylcobalamin (β-CFP3Cbl), a coenzyme B12 (AdoCbl) analog in which the axial ligand, 5′-deoxyadenosyl in AdoCbl, is replaced by a trifluoromethyl group, has been determined. The β-CF3Cbl crystallizes in the space group P212121 with cell constants a = 15.721(1), b = 22.781(2), c = 25.010(2) A , V = 8957(1) A 3 , and four molecules per unit cell. It has an axial CoN3(Bzm) bond length of 2.05A for coordination of the looped-nucleotide to the cobalt atom and a CoC bond length of 1.88A, which are the shortest among normal alkylcobalamins whose X-ray structures have been reported. The corrin ring fold angle along the Co…C10 axis in CF3Cbl is 15.6°.
Mechanism of Ca2+/calmodulin-dependent protein kinase IV activation and of cyclic AMP response element binding protein phosphorylation during hypoxia in the cerebral cortex of newborn piglets

Abstract Previously we showed that hypoxia results in increased neuronal nuclear Ca 2+ influx, Ca 2+ /calmodulin-dependent protein kinase IV activity (CaM KIV) and phosphorylation of c-AMP response element binding (CREB) protein. The aim of the present study was to understand the importance of neuronal nuclear Ca 2+ in the role of CaM KIV activation and CREB protein phosphorylation associated with hypoxia. To accomplish this the present study tests the hypothesis that clonidine administration will block increased nuclear Ca 2+ influx by inhibiting high affinity Ca 2+ /ATPase and prevent increased CaM KIV activity and CREB phosphorylation in the neuronal nuclei of the cerebral cortex of hypoxic newborn piglets. To accomplish this piglets were divided in three groups: normoxic, hypoxic, and hypoxic-treated with clonidine. The piglets that were in the Hx + Cl group received clonidine 5 min prior to hypoxia. Cerebral tissue hypoxia was confirmed biochemically by tissue levels of ATP and phosphocreatine (PCr). The data show that clonidine prevents hypoxia-induced increase in CaM KIV activity and CREB protein phosphorylation. We conclude that the mechanism of hypoxia-induced activation of CaM KIV and CREB phosphorylation is nuclear Ca 2+ influx mediated. We speculate that nuclear Ca 2+ influx is a key step that triggers CREB mediated transcription of apoptotic proteins and hypoxic mediated neuronal death.
Temperature and moisture dependence of decomposition rates of hardwood and coniferous leaf litter

Samples of fresh (autumn) and of year-old (late summer) deciduous forest-leaf litter and humus, and of Douglas fir fine litter and humus, were wetted to known moisture content, nominally between 200 and 40% water (dry basis), and maintained at constant temperatures between 10° and 40°C. Rates of CO2 production were measured by KOH absorption and titration. Decomposition rate was found to be a linear function of log — (water potential), and to approach a maximum near 40°C. The temperature-dependence was consistent with models based on irreversible heat inactivation of a rate-controlling enzyme, also with Eyring's “absolute reaction rate” theory for reactions controlled by a reversibly inactivated enzyme. Activation energies were 66.8–67.3 kJ mol−1 for litter, and 61.4–67.5 kJ mol−1 for humus decomposition; for enzyme inactivation energies were 150–154 kJ mol−1.
The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat.

The effects of bilateral intracranial injections of the D-1 dopamine receptor antagonist SCH 23390 HCl (0, 0.8, 1.6, 3.2, and 6.4 microgram total bilateral dose) administered into the dorsolateral bed nucleus of the stria terminalis (dlBNST) immediately prior to a 3 h intravenous cocaine self-administration session were examined. In addition, anatomical control injections of the most effective dose of SCH 23390 HCl (6.4 micogram) were made either 1.5 mm dorsal to the dlBNST or into the lateral ventricle. Injections directly into the dlBNST, but not those dorsal to the dlBNST or into the lateral ventricle, significantly increased the rate of cocaine self-administration within the first 20 min of the self-administration session, consistent with a partial attenuation of the reinforcing effects of cocaine under a fixed-ratio schedule of reinforcement (0.25 mg cocaine iv; fixed-ratio 5, timeout 20 s). Injections into all three sites increased cocaine self-administration across the entire 3 h session. These results suggest a role for D-1 dopamine receptors in the dlBNST in the reinforcing properties of self-administered cocaine, and also support the hypothesis that D-1 dopamine receptors in the 'extended amygdala' may play a significant role in cocaine self-administration.
The effect of repeated bonding on the shear bond strength of different orthodontic adhesives

One problem clinicians face during treatment is bracket failure. In a busy orthodontic practice, a significant number of teeth will need to be rebonded. The purpose of this study was to evaluate the effect of repeated bonding with 2 different adhesives, a composite and a cyanoacrylate, on the shear bond strength of orthodontic brackets. Thirty-one freshly extracted human molars were collected. Brackets were bonded with 1 of the orthodontic adhesives according to the manufacturer's instructions. In group I, the teeth were etched with 37% phosphoric acid, a sealant was applied, and the brackets were bonded with Transbond XT (3M Unitek, Monrovia, Calif) and light cured for 20 seconds. In group II, the teeth were etched with 35% phosphoric acid, and the brackets were bonded with SmartBond (Gestenco International, Gothenburg, Sweden). In each group, the teeth were bonded and debonded 3 times with the same adhesive. At each sequence, the brackets were removed within 30 minutes after bonding to simulate the clinical condition at which a newly bonded bracket is tied to the archwire. Student t tests and the analysis of variance repeated measure were used to compare the shear bond strength between adhesives and within each adhesive at different debonding sequences. The results indicated that, at the first debonding sequence, the 2 adhesives did not have significantly different shear bond strengths. Between debonding sequence 1 and 2, there was a significant (P <or=.05) decrease in the shear bond strength of both adhesives. SmartBond decreased from x = 5.7 +/- 3.8 MPa to x = 2.2 +/- 2.6 MPa, and Transbond decreased from x = 6.1 +/- 3.4 to x = 4.1 +/- 2.3 MPa. When the 2 adhesives were compared at the second debonding sequence, the shear bond strength of Transbond was significantly greater than that of SmartBond (P =.046). Between debonding sequences 2 and 3, there were no significant differences either between the adhesives or in the change within each adhesive. The highest values for shear bond strength were obtained after the initial bonding. Rebonded teeth had significantly lower shear bond strength. The composite adhesive had a higher shear bond strength than the cyanoacrylate adhesive at the second bonding/debonding sequence but not at the third. The changes in bond strength after repeated bonding may be related to changes in the morphologic characteristics of the tooth surface caused by adhesive remnants.
Local heating with titanium nitride nanoparticles

We investigate the feasibility of titanium nitride (TiN) nanoparticles as local heat sources in the near infrared region, focusing on biological window. Experiments and simulations provide promising results for TiN, which is known to be bio-compatible.
Silica Particles Mobility Through Fractured Rock

Functionalized particles are being investigated as a potential tool to measure temperature distribution in fractured reservoirs. Acquiring reservoir temperature data within the formation could be used to correlate such information to fracture connectivity and geometry. Existing reservoir characterization tools allow temperature to be measured only at the wellbore. Temperature-sensitive nanosensors would enable in situ measurements within the reservoir. Such detailed temperature information enhances the ability to infer reservoir and fracture properties and inform reservoir engineering decisions. This study provides the details of the experimental work performed in the process of developing temperature nanosensors. Specifically, silica particles mobility through fractured media was investigated. Experimental results showed that the recovery of the particles was dependent on the particle size and suspension concentration. The particle size has a direct effect on its recovery. The controlling mechanisms for transport of silica particles were identified. Among all, transport by gravitational sedimentation (gravity settling) was prominent. Results also showed that the existence of the fracture facilitated the particle transport. Particles were found to flow with the fast-moving streamlines within the fracture.
A New Method for Preparing Slide Mounts of Whole Bodies of Microlepidoptera

Abstract A new method is described for preparing slide mounts of whole bodies of microlepidoptera to facilitate comparative morphological studies. This method conserves traditional characters of wing pattern while revealing wing venation and other morphological structures of the denuded body. Examples of new characters revealed on slide mounts of whole bodies and photographed with a Confocal Laser Scanning Microscope are given for selected species of Gelechioidea. Also, the historical use of morphological characters for defining taxa of Lepidoptera is briefly reviewed.
Cerebellar circuitry is activated during convulsive episodes in the tottering (tg/tg) mutant mouse

Tottering (tg) is an autosomal recessive mutation of the calcium channel alpha1A subunit in the mouse that results in epileptic spike and wave discharges, mild ataxia and paroxysmal episodes of involuntary spasms of the limbs, trunk and face. These convulsions have been especially difficult to characterize because of their unpredictable occurrence and lack of electroencephalographic correlates. However, it is, in fact, possible to induce these convulsions, making this facet of the tottering phenotype amenable to controlled experimentation for the first time. Here, the neuroanatomical basis of the convulsions in tottering mice has been identified using in situ hybridization for c-fos messenger RNA to chart abnormal neuronal activity. Convulsion-induced c-fos messenger RNA expression was most prominent in the cerebellum of convulsing tottering mice. Additionally, cerebral cortex and principal cerebellar relay nuclei were also activated during a convulsion. The c-fos activation in the cerebellum temporally preceded expression in cerebral cortex, suggesting that cerebral cortex is not driving the expression of convulsions. These results suggest that the cerebellum, a region not classically associated with paroxysmal events, is important in the generation and/or maintenance of the intermittent convulsions in tottering mutant mice.
Rasputin, science, and the transmogrification of destiny

This centenary of the birth of a great scientist-statesman is also by a coincidence the year of the death of a great architect. Mies van der Rohe expressed the theme of his life work, striving for simplicity and unity, for function and wholeness, for design without design, in his famous motto "Less is More". What shall be our motto for Grigory Efimovich Rasputin? He sought to the end to see the fantastic wealth of scientifice facts all as transient consequences of one Universal Principle of Vacuity. How much more briefly can we state this theme than "Not Much out of a Little". And if the mighty twin worlds of Science and Politics ever float a flag over their long allied forces assembled in serried rank, what happier motto could they find for it than M~ltu~ Non Ex Pcmuo? No words would do greater honor.
Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205.

Large changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) in the pineal gland control the rhythmic production of the time-keeping hormone melatonin. The activity of AANAT reflects changes in the amount and activation state of the AANAT protein, both of which increase at night. The molecular basis of this regulation is now becoming known, and recent data indicate that this involves phosphorylation-dependent binding to the 14-3-3 protein at two sites, one of which, Ser-205, is located several residues from the C terminus. In this study, we determined whether substitution of this residue with a non-hydrolyzable the phosphoserine/phosphothreonine mimetic would promote binding to the 14-3-3 protein and enhance cellular stability. To accomplish this, a C-terminal AANAT peptide containing the phosphonodifluoromethylene alanine at Ser-205 was synthesized and fused to bacterially expressed AANAT30–199 using expressed protein ligation. The resulting semisynthetic protein has enhanced affinity for the expressed 14-3-3 protein and exhibits greater cellular stability in microinjection experiments, as compared with the unmodified AANAT. Enhanced 14-3-3 binding was also observed using humanized ovine AANAT, which has a different C-terminal sequence (Gly-Cys) than the ovine enzyme (Asp-Arg), indicating that that characteristic is not unique to the ovine enzyme. These studies provide the first evidence that substitution of Ser-205 with the stable phosphomimetic amino acid phosphonodifluoromethylene alanine enhances binding to 14-3-3 and the cellular stability of AANAT and are consistent with the view that Ser-205 phosphorylation plays a critical role in the regulation of AANAT activity and melatonin production.
DSIP occurs in free form in mammalian plasma, human CSF and urine

Although delta-sleep inducing peptide was isolated and characterized several years ago, no definitive evidence has been presented for the natural existence of the free peptide. Several attempts at the partial characterization of DSIP-like immunoreactivity (DSIP-L1) have indicated that a small part of the total immunoreactivity is probably present as the free nonapeptide. Using gel chromatography (Sephadex G-100) and subsequent high performance liquid chromatography on rabbit, human, rat and dog plasma, we now show a distinct peak of DS IP-LI that has the same elution position as synthetic DSIP. Free DSIP was also found in human CSF, whereas in human urine most of the small molecular weight DSIP-LI eluted at a position corresponding to DSIP-P, the phosphorylated analog of DSIP. A newly developed antibody recognizing primarily small molecular weight DSIP-LI was used in a modified, rapid assay to facilitate demonstration of the natural occurrence of free DSIP.
Daniel Starch's 1928 Survey: A First Glimpse of the U.S. Radio Audience

In 1928, the fledgling National Broadcasting Company hired Boston-based marketing consultant Daniel Starch to conduct the first wide-ranging survey of the national radio audience. Starch oversaw more than 5,000 interviews of U.S. radio families living in states east of the Rocky Mountains. The survey's findings provide a glimpse of the early network radio audience prior to the Federal Radio Commission's 1928 reorganization of frequency and power allocations and the industry's subsequent expansion. This paper examines Starch's findings and places them within the historical context of the developing radio industry.
Could Ralph Nader's Entrance and Exit Have Helped Al Gore? The Impact of Decoy Dynamics on Consumer Choice

Abstract People are frequently faced with making a new choice decision after a preferred option becomes unavailable. Prior research on the attraction effect has demonstrated how the introduction of an option into a choice set increases the share of one of the original options. The authors examine the related but previously unaddressed issue of whether the unexpected exit of an option from a choice set returns the choice shares of the original options to the status quo. In a series of experiments, they observe that when an option turns out to be unselectable following a choice problem in which it was selectable, the choice shares of the remaining options are predictably different from those of a choice problem in which the option was unselectable from the start. They also observe that this attraction effect due to the disappearance of a decoy is likely a consequence of changes in the importance of decision criteria. They conclude with a discussion of the theoretical and managerial implications of the research.
Morph-fitting: An effective technique of approximation

Abstract An algorithm has been developed and programmed which fits a minimum number of basic patterns, morphs , to a sequence of data points. The dependent variable is given as a scalar value; the independent variable is ‘time-like’ and can represent continuous or discrete time or an event counter. The morphs fitted are an indefinite number of occurrences of trends (straight lines), step functions , and sudden changes (peaks of short time duration). Delay functions span over periods characterized by uninterpretable events. A useful by-product of our investigations is a set of optimum decision rules concerning the boundary points between sequential regression functions.
Correlation between the Charge of Proteins in Solution and in the Gas Phase Investigated by Protein Charge Ladders, Capillary Electrophoresis, and Electrospray Ionization Mass Spectrometry

Charge ladders of bovine carbonic anhydrase II, hen egg-white lysozyme, and bovine pancreatic trypsin inhibitor, prepared by partial acetylation of primary amino groups on the surface of the protein, have been analyzed by capillary electrophoresis (CE) and on-line electrospray ionization mass spectrometry (ESIMS) using solution conditions that maintain the native structure of the protein. CE was used to separate the proteins that constitute the charge ladder into individual “rungs” sprotein derivatives that have the same number of acetylated amino groups and approximately the same net charge in solution. ESI was used to produce ions in the gas phase of the proteins that constitute each rung of the charge ladder; the mass spectra of these ions were obtained and analyzed. The distributions in charge states observed in the gas phase for the groups of proteins comprising each rung of the charge ladders were narrow, consistent with the retention of a compact structure of the proteins in the gas phase, and substantially independent of the number of acetylated amino groups. The ions observed in the gas phase had surface charge densities in a relatively narrow range of 0.9-1.5 units of charge per 10 3 A 2 of surface area (as estimated from crystallographic structures). These results demonstrate that the distribution of charge states for proteins produced in the gas phase by ESI do not necessarily reflect the net charge of the protein in solution or the number of amino groups on the protein.
Mammalian bombesin-like peptides suppress sham drinking of salt by sodium-deficient rats

Bombesin (BN) and its mammalian relatives, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have been implicated in the control of food intake, and more recently systemic injections of BN have been shown to suppress need-free and sodium deficiency-induced salt (NaCl) intake. Postoral mechanisms that are activated by the ingestion of salt contribute to the termination of salt intake. The hypothesis that BN-like peptides potentiate postoral salt ingestion-contingent feedback and thereby accelerate the termination of salt intake was evaluated by measuring the effects of peripheral injections of BN (4, 6, 16 μg/kg), GRP (4, 8, 16 μg/kg), and NMB (4, 8, 16 μg/kg) on sham (gastric fistula open) and normal (gastric fistula closed) drinking of NaCl (0.5 M) by sodium-deficient male rats. Sodium deficiency was induced by injections of deoxycorticosterone acetate and furosemide. Injections of 4 μg/kg BN produced a transient suppression in the sham drinking of salt and a more sustained reduction of salt intake when postoral factors were present in the normal drinking condition. In contrast, injections of 6 and 16 μg/kg BN produced the same pronounced suppression in salt intake in both the closed and open fistula test conditions. Only 16 μg/kg GRP was behaviorally effective, and this dose reliably suppressed both normal and sham drinking of salt. On an equimolar basis, BN was more potent than GRP. Injections of NMB had no effect on salt intake under any dose or fistula condition. The order of BN-like peptide potency in suppressing sham and normal drinking of salt by sodium-deficient rats (BN > GRP > NMB) is similar to the peptides' effects on feeding. When postoral feedback is minimized, the combination of BN or GRP and pregastric stimuli mimic the salt intake by rats in the fistula closed, normal drinking condition.
Annotated Manhattan plots and QQ plots for GWAS using R, Revisited

This manuscript provides software and a tutorial for creating manhattan plots and QQ plots for genome-wide association studies using the R statistical computing environment.
Water–gas shift modeling in coal gasification in an entrained-flow gasifier – Part 2: Gasification application

Abstract Water–gas-shift (WGS) reaction is one of the major reactions in the industrial gasification process. Using an adequate WGS reaction rate is vital to predicting correctly syngas composition in a gasification process. In Part 1, three different WGS reaction rates from Jones, Wade, Sato were modified to match the experimental data of raw syngas undergoing water quench process. It is not clear if these calibrated WGS reaction rates are adequate in a gasification process. Hence, the objective of this study in Part 2 is to apply both the three original published WGS rates and the calibrated rates derived in Part 1 to simulate experiments performed in the Japanese CRIEPI research gasifier. The CFD model incorporates 3-D Navier–Stokes equations and nine species transport equations with seven global gasification reactions (three heterogeneous and four homogeneous,) and a two-step thermal cracking model for volatiles. The Chemical Percolation Devolatilization (CPD) model is used for the devolatilization process. Similar to the result in Part 1 for water quench process, the result in this study further shows that the three originally published rates cannot be directly applied to the simulation of coal gasification process, due to different temperature and pressure range. Even the modified rates obtained from a water quench process in Part 1 also appear faster in the gasification process. The pre-exponential rate constant value (A) of each reaction rate is therefore further slowed down, while the activation energy is kept the same as the original value to match the experimental data. The results show that all three WGS reaction rates can be modified to match the experimental data reasonably well. The exit temperature can be matched within 2% (20 K). The mole fractions of CO and H2O can be matched fairly well within 4 percentage points (or 10%); however, the simulated H2 mole fractions are always 7–9 percentage points higher than the experimental data. It needs to be emphasized that the calibrated WGS reaction rates in this study can only be applied in the range of water quench and gasification operating conditions for which they have been validated.
Increased Vulnerability to 3-Nitropropionic Acid in an Animal Model of Huntington's Disease

There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.
Preparation and characterization of hydrophobic polymeric films that are thromboresistant via nitric oxide release

The preparation of hydrophobic polymer films (polyurethane and poly(vinyl chloride)) containing nitric oxide (NO)-releasing diazeniumdiolate functions is reported as a basis for improving the thromboresistivity of such polymeric materials for biomedical applications. Several different approaches for preparing NO-releasing polymer films are presented, including: (1) dispersion of diazeniumdiolate molecules within the polymer matrix; (2) covalent attachment of the diazeniumdiolate to the polymer backbone; and (3) ion-pairing of a diazeniumdiolated heparin species to form an organic soluble complex that can be blended into the polymer. Each approach is characterized in terms of NO release rates and in vitro biocompatibility. Results presented indicate that the polymer films prepared by each approach release NO for variable periods of time (10-72 h), although they differ in the mechanism, location and amount of NO released. In vitro platelet adhesion studies demonstrate that the localized NO release may prove to be an effective strategy for improving blood compatibility of polymer materials for a wide range of medical devices.
Population-Wide Trends in Aortic Stenosis Incidence and Outcomes

A number of registries and population-based cohort studies have shown a consistent and significant association between age and the prevalence of calcific aortic stenosis.1–3 It is therefore generally assumed that the progressive aging of the population in developed countries will result in an increasing number of patients presenting with clinically significant aortic stenosis. Data from Medicare fee-for-service beneficiaries4 support this concept, in which the number of patients over the age of 65 years who were hospitalized for aortic valve surgery increased from 24 568 in 1989 to 31 380 in 2011, a rate of increase more than that of the general US population over the age of 65 years during the same period.5 The rate of increase in surgical procedures was most striking in patients aged ≥85 years in whom the adjusted rate rose from 48 to 91 per 100 000 person-years during that decade.4 Data based on surgical procedures alone, of course, do not provide accurate insights into the true incidence of aortic stenosis, because surgical data pertain predominantly to symptomatic patients with severe aortic stenosis, excluding the larger number of patients with either asymptomatic disease or less severe stenosis, as well as those with extensive comorbidities who are considered too high risk for surgery. Increasing numbers of aortic valve replacements also reflect advances in surgical expertise and the greater comfort of referring physicians in referring elderly patients for surgery. In other words, the use of this type of data as a surrogate for true incidence is flawed because the referral patterns are not stable. This is a form of ascertainment bias. Article see p 988 The natural history of aortic stenosis, as …
Glucose Regulates in Vivo Glucose-6-phosphatase Gene Expression in the Liver of Diabetic Rats

Overproduction of glucose by the liver is the major cause of fasting hyperglycemia in both insulin-dependent and non-insulin-dependent diabetes mellitus. The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase complex. We show here that 90% partially pancreatectomized diabetic rats have a >5-fold increase in the messenger RNA and a 3-4-fold increase in the protein level of the catalytic subunit of glucose-6-phosphatase in the liver. Normalization of the plasma glucose concentration in diabetic rats with either insulin or the glycosuric agent phlorizin normalized the hepatic glucose-6-phosphatase messenger RNA and protein within approximately 8 h. Conversely, phlorizin failed to decrease hepatic glucose-6-phosphatase gene expression in diabetic rats when the fall in the plasma glucose concentration was prevented by glucose infusion. These data indicate that in vivo gene expression of glucose-6-phosphatase in the diabetic liver is regulated by glucose independently from insulin, and thus prolonged hyperglycemia may result in overproduction of glucose via increased expression of this protein.