cssi/SciSciGPT-SciSciNet huggingface dataset:
Functional studies of frataxin

Mitochondria generate adenosine triphosphate (ATP) but also dangerous reactive oxygen species (ROS). One-electron reduction of dioxygen in the early stages of the electron transport chain yields a superoxide radical that is detoxified by mitochondrial superoxide dismutase to give hydrogen peroxide. The hydroxyl radical is derived from decomposition of hydrogen peroxide via the Fenton reaction, catalyzed by Fe 2 + ions. Mitochondria require a constant supply of Fe 2 + for heme and iron-sulfur cluster biosyntheses and therefore are particularly susceptible to ROS attack. Two main antioxidant defenses are known in mitochondria: enzymes that catalytically remove ROS. e.g. superoxide dismutase and glutathione peroxidase, and low molecular weight agents that scavenge ROS, including coenzyme Q, glutathione, and vitamins E and C. An effective defensive system, however, should also involve means to control the availability of pro-oxidants such as Fe 2 + ions. There is increasing evidence that this function may be carried out by the mitochondrial protein frataxin. Frataxin deficiency is the primary cause of Friedreich's ataxia (FRDA), an autosomal recessive degenerative disease. Frataxin is a highly conserved mitochondrial protein that plays a critical role in iron homeostasis. Respiratory deficits, abnormal cellular iron distribution and increased oxidative damage are associated with frataxin defects in yeast and mouse models of FRDA. The mechanism by which frataxin regulates iron metabolism is unknown. The yeast frataxin homologue (mYfh1p) is activated by Fe(II) in the presence of oxygen and assembles stepwise into a 48-subunit multimer (a48) that sequesters >2000 atoms of iron in a ferrihydrite mineral core. Assembly of mYfhlp is driven by two sequential iron oxidation reactions: a fast ferroxidase reaction catalyzed by mYfhlp induces the first assembly step (α→α3). followed by a slower autoxidation reaction that promotes the assembly of higher order oligomers yielding α48. Depending on the ionic environment, stepwise assembly is associated with the sequestration of <50-75 Fe(II)/subunit. This Fe(II) is initially loosely bound to mYfhlp and can be readily mobilized by chelators or made available to the mitochondrial enzyme ferrochelatase to synthesize heme. However, as iron oxidation and mineralization proceed, Fe(III) becomes progressively inaccessible and a stable iron-protein complex is produced. In conclusion, by coupling iron oxidation with stepwise assembly, frataxin can successively function as an iron chaperon or an iron store. Reduced iron availability and solubility and increased oxidative damage may therefore explain the pathogenesis of FRDA.
High-resolution streamflow trend analysis applicable to annual decision calendars: a western United States case study

Changes in the seasonality of streamflow in the western United States have important implications for water resources management and the wellbeing of coupled human-natural systems. An assessment of changes in the timing and magnitude of streamflow resolved at fine time scales (days to weeks and seasons) is highly relevant to adaptive management strategies that are responsive to changing hydrologic baselines. In this paper, we present a regional analysis of the changes in streamflow seasonality through a broad classification of streams and quantification of increases and decreases in flow, based on a quantile regression methodology. This analysis affords a useful research product to examine the diversity of trends across seasons for individual streams. The trend analysis methodology can identify windows of change, thus revealing vulnerabilities within decision calendars and species lifecycles, an important consideration for adaptation and mitigation efforts.
Period-doubling Route to Multiple-pulsing in Femtosecond Fiber Lasers

An analytical model, compatible with large changes, describes soliton mode-locking in fiber lasers. The predicted period-doubling route to multiple-pulsing is confirmed experimentally. The simple model explains the remarkable observation that chaos does not follow period-doubling.
Estimation of propensity scores using generalized additive models

Propensity score matching is often used in observational studies to create treatment and control groups with similar distributions of observed covariates. Typically, propensity scores are estimated using logistic regressions that assume linearity between the logistic link and the predictors. We evaluate the use of generalized additive models (GAMs) for estimating propensity scores. We compare logistic regressions and GAMs in terms of balancing covariates using simulation studies with artificial and genuine data. We find that, when the distributions of covariates in the treatment and control groups overlap sufficiently, using GAMs can improve overall covariate balance, especially for higher-order moments of distributions. When the distributions in the two groups overlap insufficiently, GAM more clearly reveals this fact than logistic regression does. We also demonstrate via simulation that matching with GAMs can result in larger reductions in bias when estimating treatment effects than matching with logistic regression.
Bi5PO10 — A new bismuth phosphate

Abstract The title compound has been prepared for the first time and single crystals were grown by the Czochralski technique. Precession x-ray photographs indicated space groups C2, Cm, or C2/m with a = 19.642 A , b = 11.441 A , c = 21.131 A , and β = 112.37 deg.
Bidirectional emission from a ring resonator driven by an external field and containing a saturable absorber

We formulate a first-principles description of the behavior of a bidirectional ring cavity containing a saturable absorbing medium, and driven by an external coherent field. The setting of interest to this study is an extension of the ordinary optically bistable system, where a ring resonator supports only one of the two possible directions of propagation of the cavity field. In this more general case and in the uniform-field limit, we show that the dynamics of the fields-atoms system is described by an infinite set of coupled equations that can be readily solved by standard numerical means after appropriate truncation of the number of atomic variables. With the help of two different approaches, we find unexpected, long-time stationary solutions such that the forward and backward fields oscillate with different carrier frequencies: the first is based upon the time-dependent equations and the second on a set of nonlinear-algebraic equations describing the steady states. As an added confirmation, we carry out a linear-stability analysis of the unidirectional steady state for the purpose of identifying the conditions under which a backward field can grow from an initial fluctuation. By this approach we also suggest a possible strategy for the experimental observation of stationary, frequency-shifted output fields.
Gravitational Fields in Finite and Conformal Bondi Frames

We generalize the Bondi-Sachs treatment of the initial-value problem using null coordinate systems. This treatment is applicable in both finite and asymptotic regions of space whose sources are bounded by a finite world tube. Using the conformal techniques developed by Penrose, we rederive the results of Bondi and co-workers and of Sachs in conformal-space language. Definitions of asymptotic symmetry "linkages" are developed which offer an invariant way of labeling the properties of finite regions of space, e.g., energy and momentum. These linkages form a representation of the Bondi-Metzner-Sachs asymptotic symmetry group.
Quantitative assessment of intragenic receptor tyrosine kinase deletions in primary glioblastomas: their prevalence and molecular correlates

Intragenic deletion is the most common form of activating mutation among receptor tyrosine kinases (RTK) in glioblastoma. However, these events are not detected by conventional DNA sequencing methods commonly utilized for tumor genotyping. To comprehensively assess the frequency, distribution, and expression levels of common RTK deletion mutants in glioblastoma, we analyzed RNA from a set of 192 glioblastoma samples from The Cancer Genome Atlas for the expression of EGFRvIII, EGFRvII, EGFRvV (carboxyl-terminal deletion), and PDGFRAΔ8,9. These mutations were detected in 24, 1.6, 4.7, and 1.6 % of cases, respectively. Overall, 29 % (55/189) of glioblastomas expressed at least one RTK intragenic deletion transcript in this panel. For EGFRvIII, samples were analyzed by both quantitative real-time PCR (QRT-PCR) and single mRNA molecule counting on the Nanostring nCounter platform. Nanostring proved to be highly sensitive, specific, and linear, with sensitivity comparable or exceeding that of RNA seq. We evaluated the prognostic significance and molecular correlates of RTK rearrangements. EGFRvIII was only detectable in tumors with focal amplification of the gene. Moreover, we found that EGFRvIII expression was not prognostic of poor outcome and that neither recurrent copy number alterations nor global changes in gene expression differentiate EGFRvIII-positive tumors from tumors with amplification of wild-type EGFR. The wide range of expression of mutant alleles and co-expression of multiple EGFR variants suggests that quantitative RNA-based clinical assays will be important for assessing the relative expression of intragenic deletions as therapeutic targets and/or candidate biomarkers. To this end, we demonstrate the performance of the Nanostring assay in RNA derived from routinely collected formalin-fixed paraffin-embedded tissue.
Unusual lymphoproliferative disorders in nine adults with HIV or AIDS: CT and pathologic findings.

PURPOSE: To identify characteristic computed tomographic (CT) findings in unusual pulmonary lymphoproliferative disorders seen in adults with the human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans and pathologic specimens from nine patients with pulmonary lymphoproliferative disorders. CT scans were evaluated for nodules, reticulation, areas of ground-glass attenuation, consolidation, and bronchial disease. Changes seen in pathologic specimens were classified as consistent with classic lymphocytic interstitial pneumonitis (LIP), mucosa-associated lymphoid tissue lymphoma (MALTOMA), or atypical lymphoproliferative disorder (ALD). Immunopathologic results were reviewed when available. RESULTS: Eight patients had AIDS. Five patients had classic LIP. One patient had MALTOMA, and three patients had ALD. Altogether, 2-4-mm-diameter nodules were the predominant CT finding in eight patients; these were peribronc...
Comment on “222Rn Premonitory signals for earthquakes?”

Radon and other terrestrial gases in groundwater and soil air have been studied in recent years in seismically active areas, especially in China, Japan, the former Soviet Union, and the United States, in search of changes that may be useful for earthquake prediction. Concentrations of radon, helim, hydrogen, mercury vapor, carbon dioxide, and several other gases have been found to be high along active faults. Faults may thus be paths of least resistance along which terrestrial gases generated or stored in the Earth can escape into the atmosphere. Gas-concentration changes with durations of hours to months have been observed before and after earthquakes at relatively few favorably situated sites, and their patterns have not always been repeated. Some of these sites are located as far as several hundred kilometers away from earthquake epicenters. These “sensitive” sites are generally situated along active faults, whether the seismogenic ones or not, especially at their intersections or bends, or at other structurally weak zones, possibly because of concentration of tectonic strain and abundance of pore fluids at such places (see review papers byKing, 1986, 1990). Due to this selectivity and for two other important reasons, studies of terrestrial gases for earthquake prediction have not been viewed favorably by most geophysicists, especially those in the United States.
LINEAR ELASTIC BUCKLING OF PLATES SUBJECTED TO COMBINED LOADS

Abstract This paper presents a computer program for predicting the linear elastic buckling loads of plates with various loading and support conditions. The solution procedure approximates the governing differential equation by finite difference coefficients, uses these coefficients in a matrix and iteratively solves the matrix equations. The program runs within Microsoft Windows and provides graphical two and three-dimensional results of the buckled plate in addition to the plate buckling coefficient and buckling load. These results compare favorably to those listed in the reference. The program is written in C and can be easily modified to accommodate additional loading and support conditions.
A Pure-Jump Transaction-Level Price Model Yielding Cointegration

We propose a new transaction-level bivariate log-price model that yields fractional or standard cointegration. The model provides a link between market microstructure and lower-frequency observations. The two ingredients of our model are a long-memory stochastic duration process for the waiting times, {τk}, between trades and a pair of stationary noise processes, ({ek} and {ηk}), which determine the jump sizes in the pure-jump log-price process. Our model includes feedback between the disturbances of the two log-price series at the transaction level, which induces standard or fractional cointegration for any fixed sampling interval Δt. We prove that the cointegrating parameter can be consistently estimated by the ordinary least squares estimator, and we obtain a lower bound on the rate of convergence. We propose transaction-level method-of-moments estimators of the other parameters in our model and discuss the consistency of these estimators.
Reduction of non-specific binding in Ga(III) immobilized metal affinity chromatography for phosphopeptides by using endoproteinase glu-C as the digestive enzyme

The selectivity of immobilized metal affinity chromatography (IMAC) systems for the purification of phosphopeptides is poor. This is particularly a problem with tryptic digests of proteins where a large number of acidic peptides are produced that also bind during IMAC. The hypothesis examined in this work was that the selectivity of IMAC columns for phosphopeptides could be increased by using endoproteinase glu-C (glu-C) for protein digestion. Glu-C cleaves proteins at acidic residues and should reduce the number of acidic residues in peptides. This method was successfully applied to a mixture of model proteins and bovine milk. The percentage of phosphorylated peptides selected from proteolytic digests of the milk sample was increased from 40% with trypsin to 70% with glu-C. Additionally, this method was coupled with stable isotope coding methods to quantitatively compare the concentration of phosphoproteins between samples.
Study of the brittle fracture process under uniaxial compression

Abstract Static friction along inclined cracks in photoelastic models increases with both the loading and frictional displacement before the larger crack-wall asperities are broken or completely over-ridden. Elastic shocks resulting from successive stick-slip during this stage can be repeated more or less indefinitely with repeated loading and unloading. Locked-in residual stresses, especially around crack tips, result when the model is unloaded, because of frictional coupling between crack walls. Favorable crack arrays for initial growth in the model include particular sets of en-echelon cracks inclined 45° to the stress axis, but the critical orientation may be smaller in brittle rock if crack-wall friction in rock is greater than in the model. Axial growth of en-echelon cleavage cracks, inclined at angles smaller than 45°, was observed in feldspar during deformation of a pegmatite having a mineralogy and texture similar to granite. Their growth follows predictions derived from photoelastic model studies. Crack growth in the pegmatite begins between half and two-thirds of the ultimate strength. The first flaws to grow, however, also include pre-existing axially oriented cleavage cracks in the feldspar. Crack growth occurs randomly throughout the specimen as stress is increased, without much evidence that grain boundaries are activated for crack growth. But when the applied stress approaches the ultimate strength, two new features are observed. There is an abrupt development of finite frictional slip along favorably inclined flaws and grain boundaries, beginning with displacements of the order of the dimensions of grain-boundary asperities. Crack growth still occurs at various locations throughout the specimen at this stage, but there is also a detectable concentration of growth along potential shear zones. Flaw-wall friction appears to be one of the critical factors that determine the pegmatite's ultimate strength and the instability of through-going fracture.
Membranous glomerulonephritis and nephrosis post factor IX infusions in hemophilia B

Children with hemophilia B who receive exogenous factor IX infusions may rarely develop inhibitors to the exogenous factor IX and require desensitization. Nephrotic syndrome has recently been described in some of these children. We report the renal clinicopathological findings in a child with severe factor IX deficiency, requiring induction of an immune tolerance protocol, who developed nephrotic syndrome. Renal biopsy revealed peripheral capillary wall thickening and a spike appearance consistent with membranous glomerulonephritis. Electron microscopy showed prominent deposits throughout the thickness of the basement membrane. Factor IX dose reduction was accompanied by reversal of the child’s nephrotic syndrome without relapses.
Activatable Fluorescence Probes for the Cancer-Cell Specific Molecular Imaging of Cancer

Activatable fluorescence probes dramatically improve the target-to-background signal ratios compared with conventional probes. By applying such activatable probes to cancer-specific cell-surface markers it should be possible to improve the sensitivity and specificity of cancer imaging.
Auxin-induced ethylene biosynthesis in subapical stem sections of etiolated seedlings of Pisum sativum L.

1-Aminocyclopropane-1-carboxylic acid (ACC) stimulated the production of ethylene in subapical stem sections of etiolated pea (cv. Alaska) seedlings in the presence and absence of indole-3-acetic acid (IAA). No lag period was evident following application of ACC, and the response was saturated at a concentration of 1 mM ACC. Levels of endogenous ACC paralleled the increase in ethylene production in sections treated with different concentrations of IAA and with selenoethionine or selenomethionine plus IAA. The IAA-induced formation of both ACC and ethylene was blocked by the rhizobitoxine analog aminoethoxyvinylglycine (AVG). Labelling studies with L-[U-14C]methionine showed an increase in the labelling of ethylene and ACC after treatment with IAA. IAA had no specific effect on the incorporation of label into S-methylmethionine or homoserine. The specific radioactivity of ethylene was similar to the specific radioactivity of carbon atoms 2 and 3 of ACC after treatment with IAA, indicating that all of the ethylene was derived from ACC. The activity of the ACC-forming enzyme was higher in sections incubated with IAA than in sections incubated with water alone. These results support the hypothesis that ACC is the in-vivo precursor of ethylene in etiolated pea tissue and that IAA stimulates ethylene production by increasing the activity of the ACC-forming enzyme.
Wave measurement and modeling in Chesapeake Bay

Abstract Three recently measured wind and wave data sets in the northern part of Chesapeake Bay (CB) are presented. Two of the three data sets were collected in late 1995. The third one was collected in July of 1998. The analyzed wind and wave data show that waves were dominated by locally generated, fetch limited young wind seas. Significant wave heights were highly correlated to the local driving wind speeds and the response time of the waves to the winds was about 1 h. We also tested two very different numerical wave models, Simulation of WAves Nearshore (SWAN) and Great Lakes Environmental Research Laboratory (GLERL), to hind-cast the wave conditions against the data sets. Time series model–data comparisons made using SWAN and GLERL showed that both models behaved well in response to a suddenly changing wind. In general, both SWAN and GLERL over-predicted significant wave height; SWAN over-predicted more than GLERL did. SWAN had a larger scatter index and a smaller correlation coefficient for wave height than GLERL had. In addition, both models slightly under-predicted the peak period with a fairly large scatter and low correlation coefficient. SWAN predicted mean wave direction better than GLERL did. Directional wave spectral comparisons between SWAN predictions and the data support these statistical comparisons. The GLERL model was much more computationally efficient for wind wave forecasts in CB. SWAN and GLERL predicted different wave height field distributions for the same winds in deeper water areas of the Bay where data were not available, however. These differences are as yet unresolved.
Cyproheptadine prevents the initial occurence of successive negative contrast

Abstract Rats shifted from 32% to 4% sucrose make fewer licks for 4% sucrose than rats having only experienced the lower reward. In Experiment 1, the occurrence of this contrast effect was prevented by the administration of the nonspecific serotonin antagonist cyproheptadine (3.0 or 6.0 mg/kg). The results of Experiments 2 and 3 demonstrated that the contrast-reducing action of cyproheptadine was not mediated by the antiserotonergic properties of the drug since systemic administration of the serotonin synthesis inhibitor, PCPA (150 or 300 mg/kg), failed to influence either the occurence of contrast or the attenuation of contrast by cyproheptadine. The results of Experiment 4 indicated that the contrast-reducing action of cyproheptadine was not mediated by the antihistaminergic properties of the drug since the antihistamine, pyrilamine (6 or 12 mg/kg), also failed to prevent the occurence of contrast. Finally, the contrast-reducing action of cyproheptadine was not due to rate-dependent and/or appetite stimulating effects since cyproheptadine did not serve to increase lick frequency in rate-dependent controls.
Ekman, emotional expression, and the art of empirical epiphany

In the mid and late 1960s, Paul Ekman offered a variety of bold assertions, some seemingly more radical today than others (Ekman, 1984, 1992, 1993). Emotions are expressed in a limited number of particular facial expressions. These expressions are universal and evolved. Facial expressions of emotion are remarkably brief, typically lasting 1 to 5 s. And germane to the interests of the present article, these brief facial expressions of emotion reveal a great deal about people s lives. In the present article I will present evidence that supports this last notion advanced by Ekman, that brief expressions of emotion reveal important things about the individual s life course. To do so I first theorize about how individual differences in emotion shape the life context. With this reasoning as backdrop, I then review four kinds of evidence that indicate that facial expression is revealing of the life that the individual has led and is likely to continue leading.
Controls on aeolian activity: some new perspectives from the Kelso Dunes, Mojave Desert, California

Abstract The extent and intensity of aeolian processes in the Kelso aeolian geomorphic system of the Mojave Desert have varied in a complex way in time and space. Geomorphic, stratigraphic, and sedimentologic studies allow the identification of areas of relict, dormant, and active dunes. In this area, dune activity has been affected by sediment supply, climatic changes (including changes in the seasonal distribution as well as the amount of precipitation), and topographic position. Understanding of the factures that influence dune activity has been facilitated by knowledge of the history of aeolian activity and its relationship to regional environmental change.
DILTIAZEM INHIBITS HALOTHANE-INDUCED CONTRACTIONS IN MALIGNANT HYPERTHERMIA-SUSCEPTIBLE MUSCLES IN VITRO

The ability of diltiazem to suppress halothane and halothane-caffeine induced contractures in malignant hyperthermia (MH) susceptible pig muscle, was tested in vitro. Muscle specimens were divided into two groups and tested with a modified halothane-caffeine contracture test. One group acted as the control; the other group was pretreated with diltiazem 20 μmol litre−1. The control muscles developed contractures attributable to halothane and halothane-caffeine, whereas the diltiazem-treated specimens did not. Increases in muscle twitch tension as a result of halothane orhalothane-caffeine exposure occurred intreated and untreated specimens, but were significantly delayed in the presence of diltiazem. Muscle exhaustion observed after halothane and halothane-caffeine exposure in the control specimens did not occur in the diltiazem treated muscles.
Learned helplessness and the self-control model of depression.

Self-reinforcement, one element of the self-control model of depression proposed by Rehm, was evaluated as to its relationship with Seligman's learned helplessness phenomenon. Within a nonclinical population, subjects were divided by their Beck Depression Inventory scores into a Non-depressed group and a Very Mildly Depressed group. Subjects in each group were exposed to one of three treatments, Learned Helplessness, Nonlearned Helplessness, and Control conditions based upon the Levine multidimensional discrimination task. Depressed subjects gave significantly more self-punishment and less self-reward than nondepressed subjects after exposure to the experimental conditions. A significant interaction of depressed X treatment condition and post hoc analyses suggest an explanation for the previously noted facilitation effects of learned helplessness and suggest a self-control inoculation against increased depression when normals are exposed to conditions of learned helplessness. Effects of the learned-helple...
Soft Optic Modes in Barium Titanate

Phonon dispersion relations of BaTi${\mathrm{O}}_{3}$ have been measured in the cubic phase by the inelastic neutron scattering technique. The energy of the soft mode, consistent with Cochran's theory, decreases with temperature to 0.8 meV at 230\ifmmode^\circ\else\textdegree\fi{}C.
Scanning tunneling microscopy observations of Mercury droplets on graphite

Scanning tunneling microscopy surface pictures of micrometer size mercury accumulated around dislocations of graphite are presented. Mercury accumulated between linear dislocations appears to have an ordered structure ; cross sections of vertical layers are seen as small lines with atomic resolution. The distance between the small lines varies with atomic density. Mercury observed with one edge having a triangular shape smoothened with each scan. During the fifth scan a smooth edge, without any indication of the triangular edge, is seen. One and two atom thick mercury layers, due to strong interaction with the supporting graphite, are in the solid phase.
Vegetation response to climatic change in central Rift Valley, Kenya

Pollen analysis of a 15.5-m sediment core from Lake Naivasha, central Rift Valley of Kenya, reveals that the vegetation from before 20,290 to nearly 12,000 yr B.P. was dominated by open grassland, indicating arid conditions. Within this period a moderately wetter climate existed between 17,000 and 15,000 yr B.P., shown by relatively slight increase in both the montane and lowland forest vegetation. From approximately 12,000 to 6500 yr B.P., a change toward more trees and forests started at lower altitudes around the basin of Lake Naivasha, and later in the higher montane regions. After 6000 yr B.P. a decline in forest and lowland trees opened the vegetation into more grasslands and by 4000 yr B.P. a vegetation similar to the present was attained and has persisted to the present. During this period shallow-water aquatic plants became abundant in Lake Naivasha.
SU‐FF‐J‐80: Evaluation of Rotational and Translational Setup Variations for Brain Tumor Patients with Mask for Immobilization

Purpose: Rotational setup errors for braintumor patients undergoing external beam radiotherapy with a thermoplastic mask system were not well investigated and often ignored during the planning and treatment process. In this study, both translational and rotational setup variations are evaluated for braintumor patients undergoing external beam radiotherapy, using daily helical tomotherapy megavoltage computed tomography (MVCT) scans. Method and Materials: 15 primary braintumor patients who finished fractionated helical tomotherapy treatment were retrospectively selected. The number of fractions ranged from 29 to 34. Prior to each treatment fraction, an MVCT scan was performed over the brain volume. The MVCT images were registered with the planning CTimages based on bony structure using rigid translations in three dimensions and rotations in pitch, roll, and yaw. Results: The standard deviations (SD) for translations ranged 0.78 to 2.32 mm, 1.11 to 2.65 mm, and 0.52 to 6.65 mm in the RL, SI, and AP directions, respectively. The SD's ranged 0.28° to 0.83°, 0.35° to 1.04°, and 0.41° to 2.41° in pitch, roll, and yaw, respectively. 20.2%, 20.9%, and 38.9% of all the daily setups had more than 1° setup errors in pitch, roll, and yaw, respectively; and 58.4% had more than 1° errors in at least one rotational directions. 2.2%, 3.1%, and 20.9% had more than 2° setup errors in pitch, roll, and yaw, respectively, and 24.3% had more than 2° setup errors in at least one rotational directions. Residual translational setup errors in the absence of rotational setup corrections were also evaluated. Conclusion: Rotational setup variations can be significant for braintumor patients immobilized with masks, and setup corrections without rotations could lead to significant overall setup errors. Margins for treatment planning should take rotational setup variations into account. Daily image‐guided setup can be used to position the target volume.
Viability analysis of cryopreserved rat pancreatic islets using laser scanning confocal microscopy.

We have developed a digital image analysis technique to assay the viability of frozen ‐ thawed pancreatic islets by using laser scanning confocal microscopy (LSCM) in conjunction with double fluorescent staining [acridine orange/propidium iodide (AO/PI)]. Freshly isolated rat pancreatic islets were cultured for 18 ‐ 24 h and then brought to a 2 M concentration of dimethyl sulfoxide (Me2SO) by serial addition at decreasing temperatures. Ice was nucleated in the islet suspension at a defined temperature (0107C), followed by a controlled period for equilibration and then cooling in a programmable bulk freezer at rates of 0.3, 1, 3, 10, and 307C/min to0707C. Samples were then stored in liquid nitrogen. Subsequent to rapid thawing and serial dilution with sucrose solution to remove Me2SO, AO/PI-stained individual islets were prepared for imaging on the LSCM. A series of optical sections through individual stained islets were obtained and processed to obtain high-contrast images at two different wavelengths; 488 nm and 514 nm for viable and damaged tissue, respectively. Image analysis algorithms consisted of template masking, generation of histograms of the pixel intensity profile, and gray level thresholding to obtain binary images. The total percentages of both types of tissue in the islet were computed by summing the two populations in each serial section. The spatial distributions of viable and damaged tissue were calculated from the threedimensional (3-D) data base for both cultured (control) and cryopreserved islets. The 3-D spatial distributions of damaged and viable tissue in the islets were computed by determining the normalized distance of each viable/damaged voxel from the centroid of the islet volume to a mathematically estimated 3-D superquadric surface used to estimate the outer boundary of the islet. Further, each isolated damaged cell was identified and its volume determined. These studies indicate that cryopreserved islets exhibit shape distortion and a decrease in the numerical density of cells in comparison to unfrozen controls. Maximal survival was observed at the slower cooling rates. Accordingly, damage was found to occur throughout the 3-D islet volume in distinct spatial distributions for islets frozen at the slower and the faster cooling rates. Further, it was found that the volume of the majority of damaged cells identified was consistent with that of cells ranging in diameter from 5 to 9 mm. q 1996 Academic Press, Inc.
A wet-oxidation method for determination of particulate organic nitrogen on glass fiber and 0.2 μm membrane filters

Abstract A persulfate wet-oxidation method is presented for determining particulate organic nitrogen (PON) on 0.2 μm membrane filters. We evaluated the suitability of 6 types of membrane filters on the basis of filter blanks, chemical interference and adsorption characteristics. Concurrent comparisons were made using the bicinchoninic acid (BCA) protein assay. The 0.2 μm TF-200 teflon filters had low background N, no chemical interference with either assay, low N adsorption and a higher trapping efficiency than glass fiber filters (Whatman GF/F). A 20–90% increase in PON estimates for water off the coast of Oregon was found using 0.2 μm TF-200 filters compared with GF/F filters. Our results indicate that submicron PON may be a significant component of total N in seawater.
One Year Neurodevelopmental and Medical Outcomes of Persistent Pulmonary Hypertension of the Newborn (PPHN) in a Placebo Controlled Trial of Inhaled Nitric Oxide

One Year Neurodevelopmental and Medical Outcomes of Persistent Pulmonary Hypertension of the Newborn (PPHN) in a Placebo Controlled Trial of Inhaled Nitric Oxide
The California Family Health Project: II. Family world view and adult health.

This article explores the pattern of relationships between family World View and adult Health in a community based sample of 225 families. Family World View refers to the beliefs, appraisals, and values that define a family's orientation to the world. The interrelationships among eight self-reported family World View variables are described, using principal components analyses (PCA) and multidimensional scaling analyses (MDS). Derived, joint-spouse World Views also are examined using inter-battery factor analysis. The World View variables then are analyzed as a set with 14 self-reported health variables for husbands and wives separately, using canonical correlation. The PCAs for family World View yielded poor solutions for both husbands and wives. The MDS displayed the eight variables in a circular pattern for husbands and for wives, indicating the absence of a single broad dimension, or subgroupings of separate dimensions, that could be used to “describe” the domain. In the canonical analyses, family World View was a strong correlate of Health, with approximately 50% of the variance accounted for by the respective canonical variates. For husbands, what we called Family Coherence, Family Religiousness, Family Life Engagement, and Family Optimism, were correlated with Health. For wives, Family Coherence, Family Religiousness, and Family Optimism, were correlated with Health. Different patterns of health scores emerged by gender, with behavioral indicators, such as Smoking and Drinking, more salient for husbands, and mood indicators, such as Anxiety and Depression, more salient for wives.
Is the Wisconsin Card Sorting Test a useful neurocognitive endophenotype

The Wisconsin Card Sorting Test (WCST) has been utilized extensively as a measure of executive function and working memory and as a neurocognitive probe of prefrontal brain function. In studies of psychiatric illness--particularly schizophrenia--it has also been considered to be a cognitive vulnerability marker or endophenotype. Heritability is an important criterion for an endophenotype, but the very few studies of the heritability of the WCST have yielded inconsistent results. The goal of this study was to investigate the extent to which genetic and environmental factors influence WCST performance in a large adult twin sample. A computerized WCST was administered to 660 middle-aged male twins (170 monozygotic pairs and 160 dizygotic pairs). Polychoric intrapair correlations for six WCST scores were compared between MZ and DZ twins in order to assess heritability. Correlations were relatively low and there were no significant MZ-DZ differences. To our knowledge, this is the largest twin study of the WCST to date. There was no evidence for heritability of the WCST in this midlife adult sample. The WCST remains a valuable research tool, and we do not think that one should conclude from these results that genetic influences on frontal-executive function are unimportant. Rather, we believe that our results suggest that some properties of this particular test make it undesirable for use as an endophenotype.
Long-term Follow-up Outcome of Patients Undergoing Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

The long-term outcome of radiofrequency thermal ablation (RFA) for unresectable hepatocellular carcinoma (HCC) has not been reported. This study was performed to evaluate the long-term survival of patients with unresectable HCC after RFA and to identify possible factors that might affect survival. In this prospective study, 65 patients with unresectable HCC who underwent RFA were followed. A total of 84 RFA operations were performed percutaneously (n = 49), laparoscopically (n = 20), or by open surgery (n = 15), to ablate 191 tumors. Twenty-two patients died within 16 months; otherwise, the follow-up period was at least 16 months, up to 71 months, with median 20.0 months and mean (± standard deviation) 24.8 ± 18.4 months for all patients. Local tumor recurrence developed in 12 of 191 tumors (6.3%) in 11 of 84 operations (13.1%), or 11 of 65 patients (16.9%). New liver and/or extrahepatic recurrence developed in 48 operations (57.1%). The overall median, mean, and 5-year survivals were 40.0 months, 33.7 ± 2.9 months, and 39.9%. The disease-free survivals were 16.0 month, 32.9 ± 3.0 months, and 27.9%. Factors that had a significant effect on survival outcome after RFA were TNM cancer stage and the operative approach method employed for RFA. Age, gender, race, etiology, alpha-fetoprotein, previous or subsequent treatment, and liver function (Child-Pugh class) did not affect survival. For patients with unresectable HCC, RFA is an effective and repeatable local treatment that can afford long-term survival, although often with disease recurrence.
Exogenous or l-Rhamnose-Derived 1,2-Propanediol Is Metabolized via a pduD-Dependent Pathway in Listeria innocua

1,2-Propanediol (1,2-PD) added exogenously to cultures or produced endogenously from l-rhamnose is metabolized to n-propanol and propionate in Listeria innocua Lin11. The pduD gene, which encodes a diol dehydratase ss subunit homolog, is required for 1,2-PD catabolism. pduD and 16 other genes within the pduA-to-pduF region of a large gene cluster are induced in medium containing 1,2-PD.
Local and global gravitational aspects of domain wall space-times.

Local and global gravitational effects induced by eternal vacuum domain walls are studied. We concentrate on thin walls between nonequal and nonpositive cosmological constants on each side of the wall. The assumption of homogeneity, isotropy, and geodesic completeness of the space-time intrinsic to the wall as described in the comoving coordinate system and the constraint that the same symmetries hold in hypersurfaces parallel to the wall yield a general Ansatz for the line element of space-time. We restrict the problem further by demanding that the wall's surface energy density, \ensuremath{\sigma}, is positive and by requiring that the infinitely thin wall represents a thin-wall limit of kinklike scalar field configuration. These vacuum domain walls fall in three classes depending on the value of their \ensuremath{\sigma}: (1) extreme walls with \ensuremath{\sigma}=${\mathrm{\ensuremath{\sigma}}}_{\mathrm{ext}}$ are planar, static walls corresponding to supersymmetric configurations, (2) nonextreme walls with \ensuremath{\sigma}=${\mathrm{\ensuremath{\sigma}}}_{\mathrm{non}}$g${\mathrm{\ensuremath{\sigma}}}_{\mathrm{ext}}$ correspond to expanding bubbles with observers on either side of the wall being inside the bubble, and (3) ultraextreme walls with \ensuremath{\sigma}=${\mathrm{\ensuremath{\sigma}}}_{\mathrm{ultra}}$${\mathrm{\ensuremath{\sigma}}}_{\mathrm{ext}}$ represent the bubbles of false vacuum decay. On the sides with less negative cosmological constant, the extreme, nonextreme, and ultraextreme walls exhibit no, repulsive, and attractive effective ``gravitational forces,'' respectively. These ``gravitational forces'' are global effects not caused by local curvature. Since the nonextreme wall encloses observers on both sides, the supersymmetric system has the lowest gravitational mass accessible to outside observers. It is conjectured that similar positive mass protection occurs in all physical systems and that no finite negative mass object can exist inside the universe. We also discuss the global space-time structure of these singularity-free space-times and point out intriguing analogies with the causal structure of black holes.
THE CROWDING EFFECT AND MORPHOMETRIC VARIABILITY IN ECHINOSTOMA CAPRONI (DIGENEA: ECHINOSTOMATIDAE) FROM ICR MICE

Population density, or crowding, was examined to determine its effect on the morphometric variability of Echinostoma caproni (Digenea) in ICR mice. Six mice were infected with 25 and 100 metacercariae, and a single mouse was infected with 300 metacercariae. All mice were infected at necropsy 22 days postinfection with recoveries of 77%, 69%, and 7.3%, respectively. Whole mounts were prepared, and 31 characters were evaluated (25 direct measurements and 6 ratios). Univariate and multivariate statistical analysis revealed significant differences between adult worms from all 3 groups. Twenty-seven of 31 characters showed significant within-group differences, with the primary differences between worms from 25/100 versus 300 metacercariae infections. Discriminant function analysis yielded a 100% correct classification based on infection size, which is consistent with studies on distinct species of Echinostoma. The low recovery from the mouse infected with 300 metacercariae suggests inflammatory expulsion of juvenile worms and the possibility of immunity as a factor in the crowding effect. These results suggest that external factors may affect morphometric variability of digenetic trematodes to a larger degree than previously recognized.
The effects of mercury compounds on the growth and orientation of cucumber seedlings.

Mercuric chloride alone, in admixture with fluorescein or chemically combined as mercurochrome inhibited cucumber growth and induced disorientation of root and shoot. The inhibitory effects of Hg-ion were reduced but the disorienting (ageotropic) effects enhanced by the presence of fluorescein. In addition to mercury, nine other elements were tested at concentrations up to 100 mg/l (as metal ion). Disorientation was induced by Zn, Ag, Cd, In, Pt and Hg. Pb and Au were not toxic, but Ga and Tl were too inhibitory to permit disturbances in orientation.
Reaction cross sections in heavy-ion collisions

Previously a compact formula for total reaction cross section for heavy-ion collisions as a function of energy was obtained by treating the angular momentum $l$ as a continuous variable. The accuracy of the continuum approximation is assessed and corrections are evaluated. The accuracy of the compact equation can be improved by a simple modification, if a higher accuracy is required. Simple rules to determine the barrier heights and the penetration probability for the $l$ partial wave from experimental data are presented for the collision of identical or nonidentical light nuclei.
Power reduction via separate synthesis and physical libraries

We introduce the concept of utilizing two cell libraries, one for synthesis and another for physical design. The physical library consists of only 9 functions, each with several drive and beta ratio options, for a total cell count of 186. We show that synthesis performs better with the inclusion of more complex cells (but only if they are power efficient), we augment the synthesis library to include numerous combinations of the basic 9 functions. The resulting synthesis library consists of a total of 865 cells. Note that these compound cells require only characterization (for a set of drive strengths, but only one beta ratio) and no layout. After design synthesis the compound cells are decomposed back to the basic (9) cells in the physical library. Then cell-size optimization is performed. The entire flow is efficient, with an ability to handle multi-million-gate commercial designs. Applied after state-of-the-art commercial synthesis, the application of a discrete cell-size selection tool, combined with the new dual library approach, results in a typical active area reduction of 40% for large current industrial designs, for the same delay.
Abstract PR02: Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK.

Recently, we identified somatic mutations in the RAS-family small GTPase gene RIT1 in 2.4% (10/413) of lung adenocarcinoma tumors. Mutation of RIT1 is mutually exclusive with other oncogenic mutations in the receptor tyrosine kinase/RAS pathway, suggesting that RIT1 mutations are rare driver mutations in lung adenocarcinoma. Oncogenic RIT1 mutations cluster in the switch II domain of the protein and are observed not only in lung adenocarcinoma but also in myeloid malignancies, breast carcinoma, cervical carcinoma, and in the germline of Noonan syndrome patients. Here we functionally characterize 26 RIT1 point mutations and in-frame insertions/deletions in murine fibroblasts and human immortalized lung epithelial cells and find that the majority of somatic RIT1 mutations are able to transform cells. Furthermore, we identified a human lung cancer cell line, NCI-H2110, with an endogenous RIT1 p.M90I mutation. Knockdown of RIT1 in NCI-H2110 cells revealed the role of RIT1 in regulation of PI3K and MEK signaling. Consistently, combination PI3K/MEK inhibition could inhibit cellular transformation induced by ectopic expression of mutated RIT1 . Furthermore, PI3K inhibition suppressed in vivo growth of NCI-H2110 cells. These data identify RIT1 as an oncogene and nominate combined PI3K and MEK inhibition as a therapeutic strategy in RIT1 -mutated cancers. This abstract is also presented as Poster A04 . Citation Format: Alice H. Berger, Fujiko Duke, Marcin Imielinski, Nathan Kaplan, Jeremiah Wala, Geng-Xian Shi, Douglas A. Andres, Matthew Meyerson. Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr PR02.