cssi/SciSciGPT-SciSciNet huggingface dataset:
Reversal of P-glycoprotein expressed in Escherichia coli leaky mutant by ascorbic acid

It has been reported that functional expression of the multidrug resistance protein P-glycoprotein (P-gp) in E. coli is useful for screening P-gp substrates and inhibitors. In the present study, we have constructed by nitrosoguanidine and UV mutagenesis 28 leaky mutants of E. coli UT5600. These mutants are significantly susceptible to the toxic effect of known P-gp substrates and lipophilic cancer drugs. Mouse mdr1 was functionally expressed in the most permeable E. coli mutant (UTP17). Expression of P-gp in this mutant confers cross-resistance to mitomycin C, tegafur, daunorubicin, rhodamine 6G, tetraphenylphosphonium bromide and ciprofloxacin. To examine the reversal of P-gp expressed in this heterologous system, UTP17 cells expressing mouse mdr1 or lac permease as negative control were treated with various concentrations of mitomycin C with or without ascorbic acid. We found that ascorbic acid abrogated P-gp mediated multidrug resistance, suggesting that ascorbic acid might be used in combination with anticancer drugs to reduce emergence of multidrug resistance. We also demonstrated that tomato lectin antagonized the inhibitory action of ascorbic acid. This study provide a heterologous system for mdr1 expression in E. coli leaky mutant that can be used as a system for the screening of P-gp inducers and inhibitors, since it is quick and simple.
Periodic magnetospheric substorms: Multiple space‐based and ground‐based instrumental observations

[1] Quasi-periodic, sawtooth-like variations of energetic plasma particle fluxes are often measured at geosynchronous orbit during magnetic storms. The outstanding problems are whether the sawtooth flux variations represent particle injections from the tail to the inner magnetosphere, whether the sawtooth variations correspond to substorm onsets, and what mechanism is responsible for the generation of periodic particle injections (or periodic substorms). In this paper, we present the measurements of multiple space-based and ground-based instruments in the magnetosphere and ionosphere during two magnetic storms. The Geotail satellite was located in the near tail between XGSM = −20 and −30 RE and detected periodic southward turnings of the magnetospheric magnetic field. The southward turnings of Bz are interpreted as the signature of periodic near-tail reconnection and plasmoid formations. Geosynchronous satellites measured periodic gradual dropouts and rapid increases of energetic charged fluxes and magnetic field dipolarization. The IMAGE satellite measured enhanced emissions of energetic neutral atoms in the ring current and auroral brightenings. The Canadian Auroral Network for the OPEN Program Unified Study's photometers measured intensifications and latitudinal motion of auroral emissions. The auroral electrojet index showed periodic increases. These magnetospheric and ionospheric phenomena have the same periodicity and indicate the occurrence of periodic substorms. There is an excellent correspondence among the substorm signatures from all the measurements. The results show that periodic magnetospheric substorms can indeed occur during continuous southward interplanetary magnetic field, and the mean period in these two cases is ∼2.7 hours. The sawtooth variations of energetic plasma fluxes at geosynchronous orbit represent true particle injections from the tail to the inner magnetosphere. The sawtooth injections are related to the near-tail reconnection and correspond to the onsets of periodic substorms.
Lírica y novela pastoril de la Colonia: Nuevas ediciones

Grandeza Mexicana de Bernardo de Balbuena. Edicion critica de JOSE CARLOS GONZALEZ BOIXO. Roma: Bulzoni, 1988. Pp. 123. Siglo de Oro en las selvas de Erifile de Bernardo de Balbuena. Edicion, introduccion y notas de JOSE CARLOS GONZALEZ BOIXO. Xalapa: Universidad Veracruzana, 1989. Pp. 320 (mas paginas e indices de ilustraciones). Primera parte del Parnaso Antartico de obras amatorias de Diego Mexia. Edicion facsimilar. Introduccion de TRINIDAD BARRERA. Roma: Bulzoni, 1990. Pp. 276.
On piecewise reference technologies

In this paper we introduce a piecewise parametric production model that may be used as a reference technology for efficiency gauging. We show that other piecewise reference technologies used in efficiency measuring are obtained as special cases of our model.
Molecular Modeling Study Of Chiral Drug Crystals: Lattice Energy Calculations

The lattice energies of a number of chiral drugs with known crystal structures were calculated using Dreiding II force field. The lattice energies, including van der Waals, Coulombic, and hydrogen-bonding energies, of homochiral and racemic crystals of some ephedrine derivatives and of several other chiral drugs, are compared. The calculated energies are correlated with experimental data to probe the underlying intermolecular forces responsible for the formation of racemic species, racemic conglomerates, or racemic compounds, termed chiral discrimination. Comparison of the calculated energies among ephedrine derivatives reveals that a greater Coulombic energy corresponds to a higher melting temperature, while a greater van der Waals energy corresponds to a larger enthalpy of fusion. For seven pairs of homochiral and racemic compounds, correlation of the differences between the two forms in the calculated energies and experimental enthalpy of fusion suggests that the van der Waals interactions play a key role in the chiral discrimination in the crystalline state. For salts of the chiral drugs, the counter ions diminish chiral discrimination by increasing the Coulombic interactions. This result may explain why salt forms favor the formation of racemic conglomerates, thereby facilitating the resolution of racemates.
Cardiovascular-related discharge of periaqueductal gray neurons during sleep-waking states

The periaqueductal gray (PAG) contains topographically organized areas that, upon stimulation or lesion, lead to modifications in blood pressure and heart rate and redistribution of blood flow. We examined patterns of discharge of single neurons in the PAG in 5 undrugged, freely moving cats to determine if cardiovascular patterning changes observed during different sleep states were related to activity in this midbrain region. Cross-correlation histograms and linear regression techniques were used to calculate dependencies between neuronal discharge and cardiac activity. Fifty of 68 cells recorded (74%) showed a discharge timing relationship (cardiac cycle-by-cycle) and/or a tonic discharge correlation with the cardiac cycle. Nearly all (48 or 96%) of these dependencies were state related. The large proportion of neurons showing a state-related cardiac dependency suggests that the PAG may contribute to mediating different cardiac patterns observed in each state.
Relative Potencies of Polychlorinated Dibenzo-p-dioxins, Dibenzofurans, and Biphenyls Derived from Hepatic Porphyrin Accumulation in Mice

Hepatic porphyrin accumulation was studied after subchronic dosing of female B6C3F1 mice by gavage with single congeners of polychlorinated or polybrominated dibenzo-p-dioxins (PCDDs, PBDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). Quantitative hepatic porphyrin profile analyses in selected samples showed uroporphyrin and heptacarboxylporphyrin as the main porphyrins detected. Dose-dependent increases in total hepatic porphyrins were found for all congeners tested. At lower dose levels, relative potencies, based on administered dose as well as target tissue dose, of PCDDs, PCDFs, and coplanar PCBs, using 2,3,7,8-tetrachlorodibenzo-p-dioxin as a reference compound, were in the same range as those previously derived from the induction of hepatic CYP1A1 and CYP1A2 enzyme activities. CYP1A2 has been reported to be involved in the oxidation of uroporphyringen III to uroporphyrin III. All these facts suggest the involvement of an aryl hydrocarbon receptor-mediated mechanism in hepatic porphyrin accumulation, possibly via CYP1A2. However, the relative potencies of the mono-ortho-substituted PCBs were higher for hepatic porphyrin accumulation than for hepatic CYP1A1 and CYP1A2 induction. In addition, hepatic porphyrin accumulation was the highest after exposure to mono-ortho-PCBs. Since mono-ortho-substituted PCBs induce the phenobarbital-inducible CYP2B isoforms of cytochrome P450, an additional induction of δ-aminolevulinic acid synthetase may also contribute to hepatic porphyrin accumulation following subchronic exposure to these particular congeners. Relative potencies derived from hepatic porphyrin accumulation after PCDD, PCDF, or coplanar PCB administration are a useful tool in risk assessment. However, the higher relative potencies of the mono-ortho-substituted PCBs have important implications for risk assessment of these compounds.
ON THE LINEAR STABILITY OF THE INVISCID KARMAN VORTEX STREET

The classical point-vortex model for a Karman vortex street is linearly stable only for an isolated case. This property has been shown numerically to hold for other, more complicated, models of the same flow. It is shown here that it is a consequence of the Hamiltonian structure of the model, related to the codimension of the set of matrices with a particular Jordan block structure in the space of Hamiltonian matrices, and that it can be expected to hold generically for any two-dimensional inviscid array of vortices that has back-to-fore symmetry, and that is 'close enough' to the point-vortex model.
Volatile Organic Compounds in the Unsaturated Zone from Radioactive Wastes

Volatile organic compounds (VOCs) are often comingled with low-level radioactive wastes (LLRW), but little is known about subsurface VOC emanations from LLRW landfills. The current study systematically quantified VOCs associated with LLRW over an 11-yr period at the USGS Amargosa Desert Research Site (ADRS) in southwestern Nevada. Unsaturated-zone gas samples of VOCs were collected by adsorption on resin cartridges and analyzed by thermal desorption and GC/MS. Sixty of 87 VOC method analytes were detected in the 110-m-thick unsaturated zone surrounding a LLRW disposal facility. Chlorofluorocarbons (CFCs) were detected in 100% of samples collected. Chlorofluorocarbons are powerful greenhouse gases, deplete stratospheric ozone, and are likely released from LLRW facilities worldwide. Soil-gas samples collected from a depth of 24 m and a horizontal distance 100 m south of the nearest waste-disposal trench contained >60,000 ppbv total VOCs, including >37,000 ppbv CFCs. Extensive sampling in the shallow unsaturated zone (0-2 m deep) identified areas where total VOC concentrations exceeded 5000 ppbv at the 1.5-m depth. Volatile organic compound concentrations exceeded background levels up to 300 m from the facility. Maximum vertical diffusive fluxes of total VOCs were estimated to be 1 g m yr. Volatile organic compound distributions were similar but not identical to those previously determined for tritium and elemental mercury. To our knowledge, this study is the first to characterize the unsaturated zone distribution of VOCs emanating from a LLRW landfill. Our results may help explain anomalous transport of radionuclides at the ADRS and elsewhere.
Echocardiographic features of a purulent pericardial peel.

Cas d'un enfant de 2 ans 1/2 du a H. influenzae. La guerison a ete obtenue apres quelques jours de drainage et chloramphenicol intraveineux
Phases of a fermi gas with unequal spin populations

We have produced a two-component gas of ultracold, fermionic 6Li atoms with unequal spin populations. The real-space densities reveal two distinct superfluid phases, both with an evenly paired central core.
Two-Dimensional Linacs

We describe several schemes for rf acceleration of ribbon beams. (Although the ribbon edges of course, need to be focussed, these configurations are essentially 2-D.) They allow simpler modeling than quadrupole systems and, if operable, provide good matching to certain types of ion sources and beam neutralizers. We discuss four possible configurations, in chronological order of conception: (1) an rf linac with dc transverse field focussing; (2) a similar linac, also with many pairs of electrodes, but using rf focussing; (3) an RFQ-like configuration with continuous electrodes, in which energy changes slowly along the beam axis; and (4) a similar system in which the beam energy oscillates along the axis. We discuss some of the advantages and disadvantages of these systems, and analyze the last case in some detail. 8 refs., 1 fig.
Mapping of surrogate markers of cellular components and structures using laser desorption/ionization mass spectrometry.

Laser desorption/ionization mass spectrometry (LDI-MS) has been used to assess the potential of using surrogate markers, bound to cellular structures containing nucleic acids, to image or map the position of these structures within biological samples. In this study, organic dyes were used as markers because of their established use in the histochemical marking of nucleic acids, and also because they are amenable to LDI-MS. Eight cationic dyes were tested and all could be desorbed from nucleic acid samples without additional matrix after specifically binding to these molecules. Methylene Blue was the best of these based on its sensitivity to detection by LDI-MS and the fact that it can be washed from the tissue in areas where it was not specifically bound to provide low-intensity background signals. Experiments are reported which characterize the M+ ion signal obtained from Methylene Blue with regard to sensitivity, reproducibility and possible use for quantitation. This dye was used to map (with a lateral resolution of 25 µm) several nucleic acid-containing samples spotted on prepared surfaces, and to image the location of nucleic acids in two model tissues, retinal vertical sections and thyroid whole mount sections. Copyright © 2000 John Wiley & Sons, Ltd.
The ordinary URCA process in the presence of positrons and large magnetic fields

The effect of positron capture on the ordinary URCA neutrino luminosity in a zero magnetic field is investigated for several values of the degeneracy parameter and the range of temperatures 5×108K–5×1010K. The rate for this process is then compared with those in large magnetic fields (on the order ofHc =m2c3/eh=4.414×1010 G). The results indicate that positron capture reduces the effect of large magnetic fields on this process at high temperatures.
Incorporation of Functional Guest Molecules into an Internally Functionalizable Dendrimer through Olefin Metathesis

A poly(aryl ether) dendrimer bearing 22 allyl groups throughout the interior of the molecule has been prepared using a convergent synthetic approach. The internal functionalities of this dendrimer can be used to attach small molecule guests to the interior of the dendrimer using olefin metathesis. A ruthenium-based Grubbs catalyst was used to covalently attach an allylated pyrene and imidazolidinone via cross-metathesis. The extent of coupling was estimated by UV, NMR, and elemental analysis data. The high tolerance of cross-metathesis to a range of functional groups enables the incorporation of a wide range of molecules and provides access to different inner environments in one step from a single source of dendrimer.
Response to hepatitis B vaccine in Alaska natives with chronic alcoholism compared with non-alcoholic control subjects.

Abstract purpose: This study was designed to determine if (1) alcoholics have a higher prevalence of hepatitis B virus (HBV) serologic markers than do non-alcoholic controls and (2) if they respond to hepatitis B vaccination in a manner similar to that of non-alcoholic controls. patients and methods: The study was designed as a case-control study, and 129 Alaska Natives were recruited. Alcoholics were recruited from inpatient wards, outpatient clinics, a soup kitchen serving the homeless, and several alcohol rehabilitation centers; control subjects were recruited primarily from among Alaska Native Hospital employees. A standardized questionnaire, the Alcohol Dependency Scale (ADS), was administered to all participants. Each participant was screened for hepatitis B serologic markers, had liver function studies performed, and was examined for evidence of liver disease. Participants seronegative for HBV markers received three doses of hepatitis B vaccine. Linear regression analysis was performed to compare the amount of alcohol intake and variables associated with liver disease with the response to hepatitis B vaccination and antibody levels achieved. Using an ADS score of greater than 13, 64 participants were classified as chronic alcoholics, and 60 were classified as controls. results: HBV seropositivity was found in 22 alcoholics (34.4%) and seven controls (11.7%). After adjusting for age and sex, this difference was significant (χ 2 mh = 6.57, df=1; p=0.012). Abnormal levels of liver transaminase occurred significantly more often in alcoholic participants than in control subjects (χ 2 mh = 4.91, df=1; p=0.026). Of 95 seronegative persons, 72 received three doses of hepatitis B plasma-derived vaccine. Alcoholic subjects and control subjects did not differ significantly in their response to vaccination. Only four alcoholics and two controls did not develop antibody to hepatitis B surface antigen (anti-HBs) after hepatitis B vaccination, and two alcoholics and three controls had anti-HBs levels less than 10 SRU by radioimmunoassay. Mean anti-HBs levels measured in milli-international units (mIU) for the 62 responders showed a decrease in the anti-HBs level with increasing age (p 10 mIU between alcoholics and controls younger than 45 years of age, but in persons greater than 45 years of age, alcoholics had a lower mean anti-HBs log 10 mIU level than did controls; this difference, however, was not significant (p >0.10). conclusion: Chronic alcoholics have a higher prevalence of HBV seromarkers than do age-matched controls. Seronegative alcoholics, especially those under age 45, respond well to hepatitis B vaccination, and such vaccination should be considered in all chronic alcoholic persons.
O2 saturation and slings.

To the Editor. — I read with interest the recent article on cardiorespiratory stability of infants carried in slings by Stening et al.1 This is an important topic for which objective data have not been available. Unfortunately, the article suffers from a number of significant flaws. The most glaring is the definition of desaturation as a decline in oxygen concentration to <88% for at least 10 seconds. There are 10 published studies on the normal oxygen saturation of infants. In a recent review of this issue by Poets,2 it was determined that the baseline saturation of infants is 93% to 100% in term and preterm neonates and 97% to 100% in term and preterm infants; therefore, the current study has not been able to identify the number of abnormal desaturation events that occur in a sling. It is also troubling that the authors make the assumption that, in the absence of outright respiratory arrest, significant apnea, or bradycardia, chronic and/or recurrent subclinical oxygen desaturation should not be considered a “clinically relevant” event. There are published reports of both cognitive3 and behavioral difficulties4 in infants who are exposed to chronic or recurrent hypoxia. The authors therefore should be more guarded in their conclusions, because the most we can say is that there …
THE VALUE OF THE STUDIED ITEM IN THE MATCHING CRITERION IN DIFFERENTIAL ITEM FUNCTIONING (DIF) ANALYSIS

The nature of the matching criterion (usually the total score) in the study of differential item functioning (DIF) has been shown to impact the accuracy of different DIF detection procedures. One of the topics related to the nature of the matching criterion is whether the studied item should be included. Although many studies exist that suggest the studied item should always be included in the criterion, the validity of this statement for models other than the Rasch model has not been studied. This study evaluates the effect of including/excluding the studied item in the matching criterion for situations that mimic real testing situations where the assumptions of the Rasch model are violated. A simulation study was conducted where the effect of including/excluding the studied item in the matching criterion was studied relative to different magnitudes of DIF and different group ability distributions, for data that follow the two-parameter logistic (2PL) item response theory (IRT) and multidimensional item response theory (MIRT) models. Results from the study show that including the studied item leads to less biased DIF estimates and more appropriate Type I error rate, especially when the group ability distributions are different. Systematic bias positioning DIF estimation in favor of the high ability group was consistently found across all simulated conditions when the studied item was excluded from the matching criterion.
Expression of endothelial cell adhesion molecules in neovascularized tissue.

Objective:Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine-stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds. Methods:The expression of P- and E-selectin, VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10–15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mice (background). Results:Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P-selectin expression was highest in neovascularized sponge and skin. TNF-α elicited an increase...
The reluctant gamesperson — A comment on Baye, Kovenock and De Vries

My role with respect to “efficient rent-seeking”1 is an unfortunate one. Rather by accident, I discovered a new paradox in economics, something we emphatically don’t need. Various people have attempted to abolish the paradox or demonstrate that it is not very severe. My unhappy role has been pushing the discussion “Back to the Bog”.2 Although I don’t like paradoxes, I invented one and now I am defending it.
Three-dimensional culture environments enhance osteoblast differentiation.

Purpose: In previous work from our laboratory, we demonstrated that the three-dimensional (3D) cell cultures developed in simulated microgravity environments enhanced osseous-like aggregate formation and accelerated preosteoblast cell differentiation. Thus, as described here, we hypothesize that aggregate formation and mineralization would occur with fewer than 10 × 106 cells as previously described. Materials and Methods: Human preosteoblastic cells were cultured at different concentrations in a rotary wall vessel to simulate microgravity for 7 days. Aggregate size was assessed, and mineralization and collagen expression detected using Von Kossa and Masson Trichrome staining. Scanning electron microscopy was used for structural and elemental analysis. Immunohistochemistry was used to detect expression of the osteogenic markers BSPII and osteopontin (OP). Results: Size and calcium expression were dependent upon cultured cell number (p < 0.01). Calcium and collagen expression were detected throughout the aggregate, but organization was independent of cell number. Aggregates had similar microscopic structural patterns demonstrating organized development. Presence of BSPII and OP showed that the aggregates share common differentiation proteins with in vivo bone formation. Conclusions: These results may lead to novel bone engineering techniques associated with dental treatment.
A Critical Review of Estimates of Net Income from Agriculture for 1880 and 1900: New Hampshire, a Case Study

During the past twenty-five years American economic historians have made substantial progress in improving the quantitative measures of the nation's economic performance in the nineteenth century. Using New Hampshire as a case study, this paper attempts to build on this earlier research in the area of late-nineteenth-century American agriculture; the primary focus is on Richard Easterlin's estimates of state and regional income. The research reported here suggests that Easterlin's estimates need to be revised on the basis of state-level analysis and that in their present form his figures may lead to erroneous conclusions about the regional distribution of service income in late-nineteenth-century America.
A novel phenoxy thiophene sulphonamide molecule protects against glutamate evoked oxidative injury in a neuronal cell model.

Glutamate is one of the major neurotransmitters in the central nervous system. It is a potent neurotoxin capable of neuronal destruction through numerous signal pathways when present in high concentration. Glutamate-evoked excitotoxicity has been implicated in the etiology of many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and ischemic stroke. Increasing evidence has shown that reactive oxygen species (ROS) provoked by glutamate-linked oxidative stress plays a crucial role in the pathogenesis of these disorders. We previously reported the discovery of an aryl thiophene compound, 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B355252) from a proprietary library of small molecules. We showed that this compound was capable of potentiating nerve growth factor (NGF)-primed neurite outgrowth in neuronal cell models in a low NGF environment. In the present study we investigated the neuroprotective effects and signaling pathways of B355252 on glutamate-evoked excitotoxicity in HT-22, a murine hippocampal neuronal cell line. Glutamate significantly decreased HT-22 neuronal cell viability in a concentration-dependent manner as measured by the MTT assay. Co-treatment with 2, 4, and 8 μM B355252 protected against cell death caused by glutamate-induced toxicity by 9.1% (p<0.01), 26.0% (p<0.001), and 61.9% (p<0.001) respectively, compared to glutamate-treated control group. B355252 at a concentration of 8 μM fully rescued HT-22 from the neurototoxic effects of glutamate, and by itself increased cell viability by 16% (p<0.001) above untreated control. Glutamate enhanced reduction in glutathione (GSH) synthesis was reversed by 15% (p<0.01) in the presence of B355252. B355252 reduced the expression of apoptosis inducing factor (AIF) by 27%, while the proapoptotic Bcl-2 associated X protein (Bax) was strongly attenuated 3-fold. Glutamate-evoked increase in intracellular calcium (Ca2+) load and subsequent ROS production was inhibited by 71% (p<0.001) and 40% (p<0.001) respectively, to comparable level as untreated control in the presence of B355252. Glutamate significantly upregulated the phosphorylation of extracellular signal regulated kinase Erk1/2 (pERK1/2), while decreasing Erk3. In contrast, B355252 potently attenuated the glutamate-dependent activation of Erk1/2 and robustly increased the level of ERK3 in HT-22. A novel phenoxy thiophene small molecule, B355252, suppresses glutamate-evoked oxidative stress in HT-22 neurons by blocking Ca2+ and ROS production, and altering the expression or phosphorylation states of Erk kinases. This molecule previously reported to enhance neurite outgrowth in the presence of sub-physiological concentrations of NGF appears to be a promising drug candidate for development as a potential therapeutic and neuroprotective agent for various neurodegenerative disorders.
Preventing familial amyotrophic lateral sclerosis: is a clinical trial feasible?

Abstract Objective To evaluate the feasibility of a clinical trial designed to delay or prevent the onset of disease amongst subjects at risk for familial amyotrophic lateral sclerosis (fALS). Background The success of many agents in prolonging survival in the SOD1 model of ALS has not been translated into effective therapies for patients with ALS. It is our hypothesis that a trial in fALS may reproduce the positive effects seen in fALS animals. Methods Pedigrees with at least two affected family members were constructed. Unaffected family members were assigned a risk status based on their relationship to affected subjects. Attitudes towards genetic testing were ascertained amongst the at-risk family members. Results We obtained data about 5544 people (116 families) including 516 subjects with ALS (169 from SOD1 positive families) as well as 1056 subjects “definitely” or “probably” at risk for fALS (335 from SOD1 positive families). In excess of 80% of subjects indicated an interest in participating in a future clinical trial directed at delaying the onset of the disease. Assuming the use of a therapeutic agent that will prolong the time to the onset of fALS by 50%, we estimate that a sample size of between 261 and 610 subjects ‘definitely at risk’ will be required (power 0.8) depending on whether patients are followed for 10 or 5 years respectively. Conclusions A clinical trial in fALS may be feasible although such a trial would likely require prolonged follow-up and would require a therapeutic agent with a large clinical effect in order to be adequately powered.
Efficient edge detection by scale adaptation and recursive half-space filtering

A new edge detection algorithm has been developed and implemented that has both good speed and accuracy properties. The accuracy of the approach is derived from scale adaptation through anisotropic diffusion. The speed of the filter is based on recursive filtering. Specifically, the algorithm is implemented through a decomposition of the recursive filter into a convolution of two independent half space filters. This further improves the speed of the recursive filter and facilitates scale adaptation. The resulting algorithm is 1 - 2 orders of magnitude faster than comparable Gaussian based frequency domain and spatial domain methods. The new filter is omni-directional and super-elongated. It is also contour following, has computational complexity which is independent of scale, and has no truncation noise. The algorithm has been implemented and successfully applied to SPOT XS and Landsat MSS and TM imagery as one component of a region based image segmentation scheme.
Synthesis of internal standards for analytical determinations of primidone, and its metabolite, phenylethylmalonamide (PEMA)

Synthetic routes are described tor the preparation of internal standards for analytical determinations of the antiepileptic agent primidone (1) and one of its primary in vivo metabolites, phenylethylmalonamide (PEMA, 3). The internal standards synthesized in the present study are p-methylprimidone (9) and p-methylPEMA (8). The internal standards differ in structure from the parent drug and metabolite in that the phenyl substituents of the drug and metabolite have been replaced by p-tolyl substituents. The synthetic route for the preparation of p-methylPEMA (8) entailed conversion of an appropriately substituted malonate to a 4,4-disubstituted pyrazoli-dine-3,5-dione, and Raney nickel reduction of the latter substance to a malonamide. This same sequence of reactions was useful for the preparation of PEMA (3) itself. A fusion of p-methylPEMA (8) with formic acid and formamidine acetate resulted in the formation of p-methyl-primidone (9).
Pregnancy-associated hospitalizations in the United States, 1999-2000

Objective The purpose of this study was to examine nondelivery, pregnancy-associated hospitalizations in the United States and the factors associated with them. Study design Population-based nondelivery hospitalizations during pregnancy were obtained from the 1999 and 2000 National Hospital Discharge Survey. Ratios of hospitalizations per 100 deliveries were calculated and analyzed by age, race, and payment source. Results The pregnancy-associated hospitalization ratio for 1999 through 2000 was 12.8 per 100 deliveries (95% CI, 11.8-13.8). Hospitalizations were highest among young women, African American women, and women without private insurance. Preterm labor, nausea and/or vomiting, and genitourinary complications accounted for one half of antenatal hospitalizations. Conclusion Pregnancy-associated hospitalizations declined during the 1990s. This may represent a decline in maternal morbidity or a change in management of pregnancy complications. Future research should be expanded to assess trends in morbidity treated in settings outside of hospitals.
Comprehensive photoluminescence-detected magnetic-resonance study of C 60 and C 70 glasses and films

The X-band photoluminescence-detected magnetic resonance (PLDMR) of ${\mathrm{C}}_{60}$ and ${\mathrm{C}}_{70}$ films and molecules isolated in toluene/polystyrene glasses is described. The PLDMR of the glasses is due to a triplet exciton delocalized over the entire molecule. However, the PLDMR of triplet-state ${\mathrm{C}}_{70}$ ${(}^{3}$${\mathrm{C}}_{70}$) strikingly differs from that of $^{3}\mathrm{C}_{60}$ in both line shape and dynamics, due to the much longer lifetime of $^{3}\mathrm{C}_{70}$ which is consequently phosphorescent. Two distinct types of triplet excitons are detected in the PLDMR of fullerene films, one similarly delocalized over the entire molecule and a second believed to be localized on a pentagon or hexagon face adjacent to a neighboring molecule. The PLDMR line shape of the delocalized triplet is distorted due to intermolecular interactions and half-field resonances consistent with triplet-triplet fusion are detected for both triplets. A narrow (5-G-wide) PL-enhancing resonance at g=2.0017 for ${\mathrm{C}}_{60}$ and 2.0029 for ${\mathrm{C}}_{70}$ is observed and attributed to recombination of long-lived charged polarons. The PLDMR of photo-oxidized and photopolymerized films of ${\mathrm{C}}_{60}$ and ${\mathrm{C}}_{70}$ is also described. Both processes quench the PLDMR of the localized triplet, but the spectra of photopolymerized ${\mathrm{C}}_{60}$ films reveal the possibility of a third triplet exciton delocalized across several molecules.
Implementation of the centroid method of Solymosi and Dombi

Multiple objective decision support, either for selection among finite alternatives or for combining multiple functions in mathematical programming, often involves estimating a set of weights of relative importance. Recently Solymosi and Dombi proposed a means of estimating such weights based upon ordinal preference information. This method relies upon the centroid of bounded weights. Analytic hierarchy process uses ratio estimates of pairwise comparisons. Using only ordinal information, the centroid of weights is developed as an alternative means of weighting hierarchical elements. These weights could be used in selection among alternatives directly, in concordance analysis, or in multiple objective linear programming. Formulation for the centroid of feasible weight values is presented with a table of values for cases where the preference ranking includes no ties. Comparison of the technique on a student job selection decision indicates slight, but insignificant, decline in accuracy relative to the analytic hierarchy based method.
Phylogeography and evolution in matsutake and close allies inferred by analyses of ITS sequences and AFLPs.

Matsutake are commercially important ec- tomycorrhizal basidiomycetes in the genus Tricholo- ma. Despite their importance, the systematics of this species complex have remained elusive and little is known about their origin and biogeography. Using DNA analyses on a worldwide sample of matsutake, we present here the first comprehensive definition of natural groupings in this species complex. We infer patterns of migration and propose Eocene origins for the group in western North America by a transfer from an angiosperm-associated ancestor to an in- creasingly specialized conifer symbiont. From these origins, matsutake appear to have followed migratory routes parallel to those of coniferous hosts. Patterns of vicariance between eastern North America and eastern Asia are resolved and their origins are sug- gested to stem from migration through Beringia. Us- ing an analysis of genetic dissimilarity and geograph- ical distance, we reject both the possibility that mi- gration into Europe and Asia occurred through At- lantic bridges and the connection between matsutake populations in the Mahgrebi Mountains and those from Europe. Instead, African and European matsu- take appear to be the most recent ends of a westward expansion of the domain of these fungi from North
The chemistry of taxol

Abstract The chemistry of the potent anticancer diterpenoid taxol is reviewed, with an emphasis on isolation and analysis, structural modifications, partial synthesis, and structure-activity relationships.
Treatment of the neck in carcinoma of the parotid gland.

To review our experience in the treatment of the neck in patients with carcinoma of the parotid gland. A total of 263 patients were stratified into 3 groups: no neck dissection (NoND), elective neck dissection (END), and therapeutic neck dissection (TND). Clinicopathological characteristics of END and TND versus NoND were compared by Chi square test. Pathological positivity of each neck level was quantified. Neck recurrence–free survival was determined by Kaplan–Meier statistics. There were 232 cN0 and 31 cN+ patients. Of the cN0 patients, 74 had END. All cN+ patients had TND. Of the END group, occult neck metastases were detected in 26 (35 %) patients. The percentage of positivity was 6.7, 28.3, 21.3, 10.8, and 6.7 % for levels I to V, respectively. Compared to the NoND group, the END group was more likely to be over 60 years old, to have cT3T4 disease, and to have disease with more aggressive histology. Of the TND group, pathological positivity was found in 87 %. The percentage of positivity was 51.6, 77, 73, 53, and 40 % for levels I to V, respectively. Patients who had disease-positive necks had a poorer neck recurrence-free survival of 84.8 %. In patients with cN0 disease, observation of the neck is safe in those who are under 60 years of age with clinical T1 or T2 tumors and who have low-grade histology. END should be carried out in patients with cT3T4 disease or high-grade histology and should involve levels II to IV at a minimum. Patients with cN+ disease commonly have all neck levels involved and therefore should be managed with comprehensive neck dissection.
Image Mosaicking from Uncooled Thermal IR Video Captured by a Small UAV

This paper focuses on a practical technique for mosaicking video frames captured by thermal infrared (IR) cameras flown on a small Unmanned Aerial Vehicle (UAV). A Scale Invariant Feature Transform (SIFT) algorithm is used for detecting the matching feature points. Then, the k-d tree and RANSAC algorithms are used to find the best match as well as to eliminate the outliers. We propose a novel method called random M-least square to find the optimized projective transformation parameters between frames. Finally, we warp the images and adopt the multi-resolution blending method to stitch the registered frames. The whole process is applied to real UAV IR video to validate its robustness to noise and de-focusing. Also, the computational efficiency shows this method is a step in the direction of implementing a real-time UAV system.
Hypothalamic projections to cardiovascular centers of the medulla

Abstract The purpose of this project was to identify hypothalamic neurons having projections to two cardiovascular centers of the medulla, the rostral ventrolateral medulla (RVLM; a vasopressor region) and the nucleus of the solitary tract (NTS; a vasodepressor region). To accomplish this, fluorescent tracers (fast blue and diamidino yellow) were injected into NTS and RVLM, after each site had been physiologically identified in rats. In each case, one of the tracers was injected into the RVLM and another was injected into the NTS. Labelled neurons were subsequently observed along the entire rostral–caudal extent of the hypothalamus, where they were found in nuclei having known cardiovascular functions. Although the two groups of hypothalamomedullary neurons were largely overlapped in their distributions, less than 0.1% of the neurons were double labelled. In addition to this overlapping distribution of neurons, there were some areas within the hypothalamus where the two groups of hypothalamomedullary neurons were somewhat segregated. This clustering pattern was observed in the posterolateral hypothalamus (PLH) and, to a much lesser degree, in the paraventricular nucleus (PVN). Within the PLH, lying medial to the subthalamic nucleus, virtually all the labelled neurons projected exclusively to the NTS. Within the PVN, neurons projecting to the NTS were more numerous ventrally, whereas neurons projecting to the RVLM were more evenly dispersed within the PVN. In addition to hypothalamic labeling, clusters of labelled neurons were also observed in the zona incerta and the interstitial nucleus of the stria terminalis. Within the zona incerta, almost all the labelled neurons projected to the RVLM. Within the interstitial nucleus of the stria terminalis, neurons projecting to NTS were much more abundant in the dorsal portion of this nucleus; whereas, neurons projecting to the RVLM were more abundant ventrally. The findings of this study provide additional support to the notion that hypothalamic influences upon cardiovascular functions are in part mediated through hypothalamomedullary projections.
Effect of the menstrual cycle on energy and nutrient intake

Midfollicular and midluteal dietary intakes of 18 women were evaluated between four and six ovulatory menstrual cycles. Phase lengths were established by basal body temperatures and urinary luteinizing hormone excretion. Midfollicular and midluteal diet records were collected 6-8 d after menstrual onset and 6-8 d after ovulation, respectively. Significant increases in energy [0.66 MJ (159 kcal), P = 0.003], protein (6.1 g, P = 0.02), carbohydrate (15.3 g, P = 0.04), and fat (8.6 g, P = 0.002) intakes were observed in midluteal phase when compared with midfollicular phase. Intakes of vitamin D, riboflavin, potassium, phosphorus, and magnesium also were significantly higher during midluteal phase (P < 0.05). These results support the regulation of food intake by menstrual cycle hormones and suggest that it is essential to consider phase of menstrual cycle in studies of nutrient intake performed in premenopausal women.
Novel 1 kv, normally-off, vertically integrated, dual-gate VJFET power switch with a low 4.6 mωcm 2 on-state resistance

In this abstract, Northrop Grumman presents a novel monolithically integrated 1 kV normally-off VJFET power switch that combines a normally-off VJFET section with a normally-on VJFET section in a single vertical structure. The upper gates control the normally-off section while the lower-gates control the normally-on section. Depending on the specifics of the switching application, the device can be either controlled only by the upper gate in cascode configuration or be switched in shorted-gate configuration. In conclusion, Northrop Grumman has successfully developed a novel SiC, vertically integrated, 1 kV, dual-gate VJFET normally-off power switch with a low 4.6 mΩcm2 on-state resistance.
Differential effects of acute and repeated citalopram in mouse models of anxiety and depression

Clinically, SSRIs are widely prescribed in the treatment of several anxiety disorders, though very few pre-clinical studies have observed a beneficial effect of this class of drugs in animal models of anxiety. Furthermore, the biphasic pattern observed clinically, an exacerbation of anxiety followed by beneficial effects, is rarely observed in animal studies. In the present study we document this clinical phenomenon in several behavioral paradigms. While a single injection of citalopram induced anxiogenic effects, three administrations of citalopram were sufficient to elicit anxiolytic effects. Congruent with these data, we observed that short-term repeated administration with citalopram was accompanied by an increase activation of CREB in hippocampus and a desensitization of 5-HT1A receptors, two phenomenon well associated with chronic (2-3 week) rather than acute effects of antidepressants. Moreover, anxiolytic effects of citalopram were abolished in CREB αΔ mutant animals in elevated zero maze and tail suspension test, but not in novelty-induced hypophagia or 5-HT1A receptors desensitization. The significance of the elevated-zero maze and TST paradigms in predicting therapeutic efficacy is well known while effects in NIH and 5-HT1A sensitization are less well-established. These data demonstrate that behavioral response to citalopram is dependent on frequency of acministration which is associated with differences in CREB requirements.
The Effects of Low Molar Mass Diluents on the Microstructure of Ionomers

The effect of polar and nonpolar low molar mass diluents on the microstructure of lightly sulfonated polystyrene (SPS) ionomers was studied using electron spin resonance spectroscopy, small-angle x-ray scattering, and dynamic mechanical analysis. Nonpolar diluents primarily affected the hydrocarbon - rich phase, while polar diluents partitioned into the ion-rich regions and disrupted the supramolecular structure. The ionic clusters remained intact, even at elevated temperatures, upon the addition of nonpolar solvents such as dodecane and dioctylphthalate. More polar solvents such as methanol and glycerol swelled the ionic domains and promoted increased mixing of the two phases.
Predicting exposure to and uses of television violence

The uses-and-gratifications tradition posits that individual needs for stimulation and for information vary systematically. These needs may affect what media sources and other stimuli are accessed by individuals. In this study we sampled adolescents and college students to examine (a) the relation between sensation seeking and exposure to violent and nonviolent television, and (b) the subsequent role that violent television may play among high sensation-seeking adolescents in their exposure to risky behaviors. Two sensation-seeking dimensions, disinhibition (positively) and experience seeking (negatively), related to adolescents' exposure to violent television. In addition, among sensation seekers, those who exhibit risk-taking behavior were not similar to those who watched violent television, making it unlikely that the two sets of behaviors can compensate for one another. We discuss implications and directions for future research.
Potential well structures in spherical inertial electrostatic confinement devices

Inertial electrostatic confinement (IEC) devices are of interest as neutron generators for many applications. Experiments by Hirsch inspired further efforts to decipher the potential distribution within IEC devices. In this paper, previous analyzes of potential distributions in IEC devices are reviewed and extended. Three types of IEC systems are classified and analyzed according to the arrangement of electrodes and the species within the system. These systems are the unipolar cathode-anode (UCA) system, the bipolar cathode-anode (BCA) system, and the bipolar anode-cathode (BAC) system. Results of extensive parametric studies are reported through an efficient method for solving the Poisson's equation. The method is benchmarked against prior computations by Hirsch and Swanson. For BCA and BAC systems, it is concluded that the double well depth (DWD) increases as the relative focusing of the secondary particle to the primary particle increases, agreeing with prior work by Momota and Miley. Although collisions are neglected in this model, and unverified energy distributions are employed, the method generally agrees with experimental observations by Gu that the DWD will increase as the perveance of the system is increased. Thus, the computations performed here serve as a valuable benchmark.