cssi/SciSciGPT-SciSciNet huggingface dataset:
The role of scientific evidence of risks and benefits in determining risk management policies for medications

Recent changes in the regulatory environment have called attention to the need for and potential benefits of greater and more detailed evidence to inform decisions based on the risk-benefit profile of medications. Nevertheless, access to potentially beneficial therapies continues to be impeded by a lack of sufficient information that could help optimize benefits and minimize risks of treatments for patients. Over-reliance on pre-marketing clinical trials and the FDA's spontaneous reporting adverse event system to support regulatory decisions has sustained an information void. Clinical trials are the gold standard for demonstrating efficacy, but they cannot fully predict safety when drugs are used in the real world. Spontaneous reporting can identify new signals, but cannot quantify those signals or place them in appropriate clinical context. In the face of new safety signals, absence of better information on how medications are used and how they perform in the real world setting, regulators are often limited to either continuing drug marketing without significant changes or withdrawing a medication from the market. Experience shows that information collected proactively, to better understand the background risks associated with the underlying disease and to better quantify the product risks, can influence these decisions to include a wider range of options regarding a product's availability, labeling and additional risk management strategies. This article presents several case studies of medications, including those in which insufficient data were available to address important safety signals and decisions were made to withdraw products, as well as those in which epidemiologic data were available to provide reassurance of product safety and allow continued product use, even though some may be marketed with additional risk management programs. More extensive and earlier epidemiologic assessment of risks and benefits of new products will create a new standard of evidence for industry and regulators and is likely to result in more effective and balanced regulatory actions, thereby affording better care for patients.
Family Members p53 and p73 Act Together in Chromatin Modification and Direct Repression of α-Fetoprotein Transcription

Aberrant expression of the α-fetoprotein (AFP) gene is a diagnostic tumor marker of hepatocellular carcinoma. We find that AFP gene expression is repressed by the TP53 family member p73 during normal hepatic development and when p73α or p73β is introduced into cultured hepatoma cells that express AFP. Transient co-transfection of p53 family members showed that p53 and transactivating (TA)-p73, but not TA-p63, repress endogenous AFP transcription additively or independently. p53-independent functions of p73 are further supported by delayed, p73-associated compensation of AFP repression during development of the p53-null mouse. Chromatin immunoprecipitation assays of normal and p53-null mouse liver tissue showed that TA-p73 binds at a previously identified p53 repressor site (-860/-830) within the distal promoter of AFP at a level equivalent to p53 in wild type liver, with increased binding of TA-p73 to chromatin in the absence of p53. Sequential chromatin immunoprecipitation analyses revealed that TA-p73 and p53 bind simultaneously to their shared regulatory site in wild type liver. Like the founding family member p53, TA-p73 represses AFP expression by chromatin structure alteration, targeting reduction of acetylated histone H3 lysine 9 and increased dimethylated histone H3 lysine 9 levels. However, chromatin-bound TA-p73 is associated with elevated di- and tri-methylated histone H3 lysine 4 levels in p53-null liver and hepatoma cells, concomitant with a reduced ability to repress transcription compared with p53.
Initial Assessment of the Effects of Radiation on the Electrical Characteristics of ${\rm TaO}_{\rm x}$ Memristive Memories

Radiation-induced effects on the electrical characteristics of TaOx memristive (or redox) memory are experimentally assessed. 10 keV x-ray irradiation is observed to cause switching of the memristors from high to low resistance states, as well as functional failure due to cumulative dose. Gamma rays and 4.5 MeV energy protons are not observed to cause significant change in resistance state or device function at levels up to 2.5 Mrad(Si) and 5 Mrad(Si) protons, respectively. 105 MeV and 480 MeV protons cause switching of the memristors from high to low resistance states in some cases, but do not exhibit a consistent degradation. 800 keV silicon ions are observed to cause resistance degradation, with an inverse dependence of resistance on oxygen vacancy density. Variation between different devices appears to be a key factor in determining the electrical response resulting from irradiation. The proposed degradation mechanism likely involves the creation of oxygen vacancies, but a better fundamental understanding of switching is needed before a definitive understanding of radiation degradation can be achieved.
Diagnosis of Cavernous Sinus Artenovenous Fistula by Measurement of Ocular Pulse Amplitude

Background: The ocular pulse amplitude (OPA), the difference between the maximum and minimum intraocular pressure (IOP) during the cardiac cycle, has been reported to be elevated in the eye ipsilateral to a cavernous sinus arteriovenous fistula. Methods: The OPA was measured with a pneumotonometer in three groups of patients. Patients in group 1 had no orbital disease (n = 50), patients in group 2 had either unilateral or asymmetric orbital disease (n = 30), and patients in group 3 had angiographically proven cavernous sinus arteriovenous fistulas (n = 15). Results: Patients in group 3 had a higher OPA than patients in either group 1 ( P P P Conclusion: A ΔOPA of more than 1.6 mmHg was 100% sensitive and 93% specific in identifying patients with cavernous sinus arteriovenous fistulas. There was no difference in ΔOPA between direct and dural cavernous sinus arteriovenous fistulas. Successful transvascular embolization of the cavernous sinus arteriovenous fistula normalized the ΔOPA by reducing the OPA on the affected side.
Monitoring, planning, and self-efficacy during learning with hypermedia: The impact of conceptual scaffolds

Self-report data and think-aloud data from 37 undergraduates were used to examine the impact of conceptual scaffolds on self-efficacy, monitoring, and planning during learning with a commercial hypermedia environment. Participants, randomly assigned to either the No Scaffolding (NS) or Conceptual Scaffolding (CS) condition, used a hypermedia environment for 30min to learn about the circulatory system. Think-aloud data collected during this learning task was used to measure participants' self-regulated learning (SRL) with hypermedia. Additionally, participants completed a self-efficacy questionnaire at three points during the learning task (immediately prior to the 30-min hypermedia learning task, 10min into the learning task, and 20min into the learning task). Results indicated that participants from both conditions reported higher levels of self-efficacy immediately before the hypermedia learning task, and that they decreased their use of SRL processes related to monitoring as they progressed through the hypermedia learning task. In addition, results also indicated that participants in the CS condition used, on average, more SRL processes related to planning during the hypermedia learning task than participants in the NS condition.
Acoustics of Transonic Flow Around an Oscillating Flap

Investigation of noise mechanisms due to unsteady transonic flow is important for aircraft noise reduction. In this work, the near-field impulsive noise due to an oscillating flap is simulated numerically. The problem is modeled by the two-dimensional high frequency transonic small disturbance equation (VTRAN2 code). The three types of unsteady shock wave motion have been identified. Two different important disturbances exist in the pressure signal. The disturbances are related to the unsteady motion of the supersonic pocket and fluctuating lift, and drag forces. Pressure wave signatures, noise frequency spectra, and noise directivity are shown.
Use of Carborundum for Ruling Test Plates

THE communication from Mr. A. Mallock in NATURE of September 1, p. 10, reminds me of the marked success that I have had in the use of fine carborundum points for scratching on glass. Some years ago, when confronted with the task of preparing small oscillograph mirrors from microscope cover-glasses, I found that a small fragment of carborundum crystal tied in the split end of a match or forced into a piece of soft rubber for a handle made an excellent glass-cutter. The scratches were so fine and clean-cut that the glass could easily be broken into very narrow strips.
Traitement hybride des anévrysmes aortiques englobant les artères viscérales et rénales

Rationnelle Nous souhaitions analyser notre experience du traitement hybride des anevrysmes aortiques englobant les arteres renales et viscerales. Methodes Nous avons mene une revue retrospective de 36 patients consecutifs qui avaient eu des pontages renaux/visceraux suivis par la mise en place d’endoprotheses aortiques. Les donnees demographiques des patients, l’histoire medicale, les interventions, les complications, la permeabilite prothetique, et la survie des patients etaient recueillies. Une analyse observationnelle et comparative etait realisee. Resultats L’âge moyen des patients etait de 71 ans. Le diametre anevrysmal moyen etait de 6,3 cm (range 4,1-9,4 cm). Selon la classification de Crawford, il y avait 1 type I, 10 type II, 12 type III, 10 type IV, et 3 anevrysmes pararenaux. Quatre patients etaient symptomatiques. Cent vingt-trois pontages etaient realises (mediane: 3/patient), dont 62 arteres renales, 32 arteres mesenteriques superieures, et 29 troncs cœliaques. Une revascularisation retrograde (via les arteres iliaques, l’aorte, ou un jambage de prothese aorto-bi-femorale) etait utilisee chez 30 patients et une revascularisation anterograde etait utilise chez six patients (trois a partir de l’aorte supracœliaque, et trois pontages renaux a partir de branches de tronc cœliaque). La mortalite hospitaliere etait de 8,3% (3 patients). Avec un suivi moyen de 6 mois, la survie etait de 80%. Une complication morbide majeure survenait chez 17 patients (47%), dont la necessite de dialyse (5), l’ischemie colique (3), l’alteration de l’etat general (5), la paraparesie temporaire (1), et la reintervention (7). Aucun patient n’a presente de paraplegie permanente. La duree moyenne de sejour etait de 26 jours (range 8-100 jours). La permeabilite primaire des pontages reno-visceraux etait de 93% a 8 mois. Au cours du suivi, 14 patients developpaient au moins une endofuite, 2 patients necessitaient une intervention percutanee, et les autres restaient en observation. Au dernier suivi, quatre endofuites de type 2 et une endofuite de type 3 etaient notees avec un anevrysme stable ou en diminution. Conclusion Le traitement hybride des anevrysmes aortiques englobant les arteres renales et viscerales est faisable avec une mortalite raisonnable et des taux de permeabilite satisfaisants a court terme concernant les pontages reno-visceraux. Cependant la morbidite des procedures de deroutage est elevee. Une selection plus stricte des patients pourrait ameliorer ces resultats.
Multifunctional Remote Laboratories for Real Experiments, Engineering Processes, and Manufacturing Methods

This paper describes the efficient structures of various multifunctional remote laboratories for real experiments, engineering processes, and manufacturing methods. Some theoretical problems concerning functional completeness, universality, flexibility, and programmability of such remote laboratories and facilities are discussed in the framework of a new interdisciplinary scientific approach called general formal technology (GFT). GFT is a branch of general system theory (GST). It correlates with Alexander Bogdanov’s Tektology and can be used to investigate formal algorithmic and physical system structures for the synthesis and analysis of various objects.
A theoretical derivation of the dependence of the remotely sensed reflectance of the ocean on the inherent optical properties

An expression for the ratio of the upwelling nadir radiance L(pi, z) and the downwelling scalar irradiance E(sub od)(Z) is derived from the following equation of radiative transfer. This expression is given by RSR(z) = (L(pi, z))/E(sub od) = (f(sub b)(z)b(sub b)(z))/2 pi(k(pi, z) + c(z) - F(sub L)(z)b(sub f)(z)), where b(sub b)(z) is the backscattering coefficient, k(pi, z) is the vertical attenuation coefficient of the nadir radiance, c(z) is the beam attenuation coefficient, and f(sub b)(z) and f(sub L)(z) are shape parameters that depend on the shape of the volume scattering function and the radiance distribution. Successive approximations are subsequently applied to the above exact equation. These are f(sub b)(z) = (2 pi beta(pi - theta(sub m), z)/(b(sub b)(z))), where beta(pi - theta(sub m), z) is the volume scattering function at 180 deg minus the zenith angle of the maximum radiance, and k(pi, z) = am = c(1 - 0.52 b/c - 0.44 (b/c)(exp 2)), where m is a parameter that is numerically equal to the inverse of the average cosine of the asymptotic light field for a medium with the same inherent optical properties, a is the absorption coefficient, and b/c is the single scattering albedo. Together with f(sub L)(z) = 1.05 and application of Gershun's equation, it is shown that for nearly all oceanic cases RSR(z) identical to L(pi, z)/E(sub od)(z) = (Beta(pi - theta(sub m), z))/(a(z)(1 + m(z))).
Ars2 Promotes Proper Replication-Dependent Histone mRNA 3′ End Formation

Ars2 is a component of the nuclear cap-binding complex that contributes to microRNA biogenesis and is required for cellular proliferation. Here, we expand on the repertoire of Ars2-dependent microRNAs and determine that Ars2 regulates a number of mRNAs, the largest defined subset of which code for histones. Histone mRNAs are unique among mammalian mRNAs because they are not normally polyadenylated but, rather, are cleaved following a 3' stem loop. A significant reduction in correctly processed histone mRNAs was observed following Ars2 depletion, concurrent with an increase in polyadenylated histone transcripts. Furthermore, Ars2 physically associated with histone mRNAs and the noncoding RNA 7SK. Knockdown of 7SK led to an enhanced ratio of cleaved to polyadenylated histone transcripts, an effect dependent on Ars2. Together, the data demonstrate that Ars2 contributes to histone mRNA 3' end formation and expression and these functional properties of Ars2 are negatively regulated by interaction with 7SK RNA.
Design Innovation Size and Shape Optimization of a 1.0mm Multifunctional Forceps-Scissors Surgical Instrument

A size and shape optimization routine is developed for a 1.0 mm diameter multifunctional instrument for minimally invasive surgery. The instrument is a compliant mechanism capable of both grasping and cutting. Multifunctional instruments are expected to be beneficial in the operating room because of their ability to perform multiple surgical tasks, thereby decreasing the total number of instrument exchanges in a single procedure. With fewer instrument exchanges, the risk of inadvertent tissue trauma as well as overall surgical time and costs are reduced. The focus of this paper is to investigate the performance effects of allowing the cross-sectional area along the length of the device to vary. This investigation is accomplished by defining various cross-sectional segments in terms of parametric variables and optimizing the dimensions of the instrument to provide a sufficient opening of the forceps jaws while maintaining adequate cutting and grasping forces. Two optimization problems are considered. First, all parametric segments are set equal to one another to achieve size optimization. Second, each segment is allowed to vary independently, thereby achieving shape optimization. Large deformation finite element analysis and optimization are conducted using ANSYS®. Finally, prototypes are fabricated using wire EMD and experiments are conducted to evaluate the instrument performance. As a result of allowing the cross-sectional area to vary, i.e., conducting shape optimization, the forceps and scissors blocked forces increased by as much as 83.2% and 87%, respectively. During prototype evaluations, it is found that the finite element analysis predictions were within 10% of the measured tool performance. Therefore, for this application, it is concluded that performing shape optimization does significantly influence the performance of the instrument.
Female preferences for large, heavy mates in Schistocerca americana (Orthoptera : Acrididae)

The significance of female choice in shaping mating systems remains problematic. The following study clearly documents female preferences in a species of grasshopper,Schistocerca americana, over the course of 3 years. Three sets of animals were observed in an outdoor seminatural cage. Females were found to mate more often with large, heavy males. Furthermore, remating by a female within a week was less likely if she mated with a large or heavy male. Because females were found to oviposit 2 days after a mating on average, these large heavy males may also be chosen cryptically (as defined in the literature) and father more offspring.
A study of basis set effects on structures and electronic structures of phosphine oxide and fluorophosphine oxide

A variety of basis sets have been used for geometric and electronic structure studies. Electronic effects were measured using integrated spatial electron populations (ISEP). The two largest basis sets used, 6-31G* and DZ+P, give significantly different results. Use of two d-orbital sets (6-31G*[dd]) or decontraction of the 2sp shell on phosphorus has little further effect. d-Orbitals on oxygen are required for consistent electronic structure results, and d-orbitals on fluorine have a small but significant effect. Use of diffuse functions, required for anions, is not recommended with small basis sets on neutral molecules. Large negative charges (≈−1.5) on oxygen are given by all of the larger basis sets by the ISEP procedure and indicate that the PO bond in these compounds is largely semi-polar. The best simple symbolic representation of phosphine oxide is H3P+0−, rather than H3P0.
Rhenium Complexes with Weakly Coordinating Solvent Ligands, cis-[Re(PR3)(CO)4(L)][BArF], L = CH2Cl2, Et2O, NC5F5: Decomposition to Chloride-Bridged Dimers in CH2Cl2 Solution

The solvent-coordinated complexes [cis-Re(CO)4(PR3)(S)][BArF] (R = Ph, iPr, Cy, BArF = [B(3,5-(CF3)2C6H3)4]-) for S = Et2O, CH2Cl2, and NC5F5 have been prepared from reaction of the neutral methyl precursors, cis-Re(CO)4(PR3)(Me), with either [H(OEt2)2][BArF] or [Ph3C][BArF] in the appropriate solvent. A crystal structure of the complex [cis-Re(CO)4(PiPr3)(ClCH2Cl)][BArF] shows that the dichloromethane ligand is coordinated through one chlorine, with an Re−Cl distance of 2.554(2) A. The first example of a structurally characterized pentafluoropyridine complex of rhenium was also determined, [cis-Re(CO)4(PiPr3)(NC5F5)][BArF], with an Re−N distance of 2.319(5) A. Activation of C−Cl bonds in the dichloromethane complexes result in the formation of the chloride-bridged dimers, {[cis-Re(CO)4(PR3)]2(μ-Cl)}{BArF}, and the X-ray structures of the Ph and Cy derivatives were determined.
NIFTY (NeuroImaging Functional Toolkit): an interactive program for functional MRI data processing and visualization

NIFTY (NeuroImaging Functional Toolkit) is a tool designed to perform quantitative analysis and visualization of neurofunctional magnetic resonance image (fMRI) data sets. NIFTY is an OSF/Motif application which utilizes the AVW (a visualization workshop) imaging library developed in our laboratory and includes algorithms for robust image registration, statistical analysis, and mapping of neurofunctional data sets. Anisotropic diffusion routines can be used to enhance the signal-to-noise- ratio of these images. Tools capable of histogram equalization, thresholding, volume rendering, atlas matching, and a large number of other functions can then be used to visualize the data. NIFTY's development will offer a robust and flexible system of essential functions integrated into an interactive, graphically-oriented program, allowing neuroscientists the means by which to process, visualize, and interpret their data.
Persistent Anomalies of the Extratropical Northern Hemisphere Wintertime Circulation: Structure

A study identifying horizontal and vertical structures of low patterns occurring with persistent 500 mb height anomalies in the central North Pacific, eastern North Atlantic, and northern Soviet Union regions is presented. The flow patterns of positive and negative anomalies are compared. The relationship between persistent anomalies and small recurrent anomaly patterns is examined. The temporal fluctuations of the persistent patterns are analyzed.
Impaired performance by post-trial injections of cycloheximide in a passive avoidance task

Cycloheximide, injected subcutaneously after training in a passive avoidance task resulted in impaired performances on the retest given 7 days later. A gradient was observed for this effect, injections given immediately after training producing most impairment and injections given 2 h after training producing none.
Absolute configuration of an allenic enzyme inactivator

Abstract X-Ray crystallographic analysis of the 4-(4′-bromophenyl)phenacyl ester of (+)-2,3-decadienoic acid has shown that the allenic inhibitor of β-hydroxy-decanoylthioester dehydrase has the S configuration.
The Quantum Pair of Pants

We compute the spectrum of the operator of multiplication by the complex coordinate in a Hilbert space of holomorphic functions on a disk with two circular holes. Additionally we determine the structure of the C -algebra generated by that operator. The algebra can be considered as the quantum pair of pants.
Adaptation and dynamics in X-cells and Y-cells of the cat retina.

On the basis of the spatial summation properties of their receptive fields, cat retinal ganglion cells were classified as either X-cells (linear) or Y-cells (non-linear). Responses were then obtained to a small, centered spot, square-wave modulated in time and superimposed on various levels of diffuse, steady background illumination. When fully dark-adapted, both X-cells and Y-cells produced responses that were entirely sustained. When well lightadapted but still in the scotopic range, both cell types produced largely transient responses with only a very small sustained component. The sustained or transient nature of responses is, therefore, not an invariant characteristic of X-cells and Y-cells in the scotopic range. We also conclude that the mechanism which controls the center's sensitivity in the scotopic range is similar though not identical in the two types of cells.
Defect Structure of Crystalline Quartz. II. Variation of Displacement Threshold Energy with Crystal Growth Rate

An optical-absorption maximum ($C$ band) is produced at about 220 m\ensuremath{\mu} in crystalline quartz by electron bombardment at 77\ifmmode^\circ\else\textdegree\fi{}K. The band is produced by the displacement of lattice atoms and not by ionization. Previously it was shown that the production rate of the band for constant integrated electron flux increases greatly with increased growth rate. In the present experiment, the threshold energy for the displacement which leads to $C$-band absorption was measured in synthetic crystalline quartz grown at 0.45 and 1.91 mm/day. Interpretations of the data lead to the conclusion that $C$-band absorption is caused by displacement of oxygen atoms and that the threshold energy for this displacement is a function of growth rate varying from 15\ifmmode\pm\else\textpm\fi{}5 eV for fast-growth (1.91 mm/day) material to 50\ifmmode\pm\else\textpm\fi{}5 eV for quartz grown at a slower rate (0.45 mm/day).
Atomically detailed simulations of surface resistances to transport of CH4, CF4, and C2H6 through silicalite membranes

Abstract We have used atomically detailed methods to examine the surface resistances associated with single-component permeation of CH 4 , CF 4 , and C 2 H 6 through single crystal silicalite membranes. Dual control volume grand canonical molecular dynamics (DCV-GCMD) simulations can be used for this purpose, but only for extremely thin membranes and for relatively rapidly diffusing species. We use calculations of this type to introduce a more computationally efficient but approximate method for describing surface resistances, the local equilibrium flux method (LEFM). Using LEFM calculations, it is possible to accurately and rapidly predict surface resistances for large ranges of membrane operating conditions. Using this approach, we identify the crystal thicknesses beyond which surface resistances are negligible for single-component permeation of CH 4 , CF 4 , and C 2 H 6 through silicalite membranes as functions of membrane feed and permeate pressure.
Anaesthesia for ventricular aneurysmectomy

Our technique of anaesthesia for resection of ventricular aneurysms is described, The haemodynamic changes which lead to decreased oxygen availability, increased oxygen consumption, and decreased cardiac output are kept in mind. Thiopentone, curare, and methoxyflurane are administered in doses which provide adequate anaesthesia and avoid myocardial irritability or depression. Careful attention is given to maintaining coronary dilatation and improving tissue perfusion by deliberate use of coronary vasodilators. Blood gases, pH, and electrolytes, especially potassium, are monitored and maintained within normal limits, both during operation and postoperatively. Pharmacological support and return to partial cardiopulmonary bypass employed when the heart function is inadequate, are also discussed. The importance of monitoring left atrial pressure and correlating it with central venous pressure and mean blood pressure is emphasized. Evaluation of the amount of transfusion, status of the myocardium, and the need for and the effectiveness of drug therapy are based on these observations. Postoperative arrhythmias are to be treated promptly and specifically. Prevention and management of postoperative respiratory complications are of the utmost importance.
PRICKLE DISTRIBUTION IN ARALIA SPINOSA (ARALIACEAE)

The density of Aralia spinosa prickles varied with the age and architectural position of annual increments. Prickles were most common on young (1-4 years old, 2-3 m tall), unbranched stems. Prickles were less common on branches and were absent on inflorescences. Ramets that grew as sprouts after injury had more and longer prickles than ramets that had not arisen in this way. Leaf prickles were also more common on the leaves of trunk annual increments than on the leaves of branch annual increments. As with stem prickles, leaf prickles were more common on the leaves of stems that had sprouted after cutting than on the leaves of ramets that had not been previously cut. As bark developed, stem prickles were lost at a rate of about 10% per year. While dense prickles characterized young individuals, older individuals (> 15 years old) had very few prickles. ARALIA SPINOSA L. is a small tree of disturbed patches in the deciduous forests of eastern North America. Among Aralia's distinctive traits are large, bi-tripinnately compound, leaves, large terminal inflorescences, and abundant prickles on stems and leaves. While engaged in a study of the shoot architecture of Aralia spinosa (White, 1984), I noted that young, unbranched individuals were often more densely prickly than older Aralia individuals in the same population. I therefore posed the question: is the change in armature related to architectural development in Aralia? The shoot architecture of Aralia is distinctive (White, 1984). During the first three to five years of growth (the "trunk-building" phase), the ramet grows upward at 75 cm per year and is sterile and unbranched. During this phase, the spread of leaf area is accomplished entirely by means of the large, compound leaves. On average the ramets flower in their third or fourth year. The year after flowering, branches develop and the ramet slows greatly in annual extension growth. This study characterizes the distribution of Aralia prickles in space (i.e., their distribution relative to stem height and architecture) and time (i.e., their production, persistence, and relation to ramet development and bark formation).
α-Tocopherol regulation of hepatic cytochrome P450s and ABC transporters in rats

To test the hypothesis that supra-elevated hepatic alpha-tocopherol concentrations would up-regulate mechanisms that result in increased hepatic alpha-tocopherol metabolism and excretion, rats received daily subcutaneous alpha-tocopherol injections (10 mg/100 g body wt) and then were sacrificed on Day 0 or 12 h following their previous injection on Days 3, 6, 9, 12, 15, and 18. Liver alpha-tocopherol concentrations increased from 12 +/- 1 nmol/g (mean +/- SE) to 819 +/- 74 (Day 3), decreased at Day 9 (486 +/- 67), and continued to decrease through Day 18 (338 +/- 37). alpha-Tocopherol metabolites and their intermediates increased and decreased similarly to alpha-tocopherol albeit at lower concentrations. There were no changes in known vitamin E regulatory proteins, i.e., hepatic alpha-tocopherol transfer protein or cytochrome P450 (CYP) 4F. In contrast, both CYP3A and CYP2B, key xenobiotic metabolizing enzymes, doubled by Day 6 and remained elevated, while P450 reductase increased more slowly. Consistent with the decrease in liver alpha-tocopherol concentrations, a protein involved in biliary xenobiotic excretion, p-glycoprotein, increased at Day 9, doubling by Day 15. Thus hepatic alpha-tocopherol concentrations altered hepatic proteins involved in metabolism and disposition of xenobiotic agents.
69,71Ga and 14N high-field NMR of gallium nitride films

Gallium nitride thick films produced by HVPE having varying levels of defects have been characterized by 69,71Ga and 14N NMR at high field (11.7 T). The highest quality film yields the sharpest NMR peaks, from which highly accurate NMR parameters, viz. nuclear quadrupole coupling constants (NQCC), isotropic chemical shifts and chemical shift anisotropies, could be derived from studies as a function of film orientation. Poorer quality films (larger X-ray rocking curve widths) exhibit markedly broader 71Ga satellite transition peaks with a longer T2 relaxation time, and additional high-frequency shoulders or peaks for the central transitions. The linewidths of the 14N doublet are also broader in the poorer quality films. The 71Ga spectra of films containing high oxygen levels show a new high-frequency central-transition peak with a very short T1. The high-frequency peaks in all cases may be due to Knight shifts arising from conduction electrons. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamics of discrete distribution for Smoluchowski coagulation model

Abstract A new mathematical approach to the dynamics of a coagulation model with the collision frequency coefficient independent of particle size is presented. The technique consists in developing differential equations for the moments of the discrete distribution of the particle size, which allows an exact analytical solution for the dynamics of the size distribution to be determined. Analysis of this solution provides additional proof for the self-preserving hypothesis. The main novelty of the approach is the development of the criteria for the time required to attain the asymptotic distribution for both monodisperse and polydisperse initial distributions.
Active Combustion Control for Aircraft Gas Turbine Engines

Lean-burning combustors are susceptible to combustion instabilities. Additionally, due to non-uniformities in the fuel-air mixing and in the combustion process, there typically exist hot areas in the combustor exit plane. These hot areas limit the operating temperature at the turbine inlet and thus constrain performance and efficiency. Finally, it is necessary to optimize the fuel-air ratio and flame temperature throughout the combustor to minimize the production of pollutants. In recent years, there has been considerable activity addressing Active Combustion Control. NASA Glenn Research Center's Active Combustion Control Technology effort aims to demonstrate active control in a realistic environment relevant to aircraft engines. Analysis and experiments are tied to aircraft gas turbine combustors. Considerable progress has been shown in demonstrating technologies for Combustion Instability Control, Pattern Factor Control, and Emissions Minimizing Control. Future plans are to advance the maturity of active combustion control technology to eventual demonstration in an engine environment.
Excimer laser ablation of Cr-contaminated polyimide

Excimer laser radiation at 193 and 248 nm has been used for the maskless and selective removal of chromium (Cr) contaminants present on polyimide surfaces with fine-line gold (Au) metallization features patterned on them. Excimer laser cleaning has been successful in restoring the dielectric performance of these polyimide surfaces. The differences in ablation thresholds and rates and the respective process windows, established at 193 and 248 nm, for the removal of Cr are discussed.
A novel PD model for gatifloxacin (GF) vs. salmonella typhi (ST) in timed kill curves (KC)

Quinolones are the mainstay of treatment for ST infections but there is growing concern about resistance to older quinolones & poor understanding of quinolone/ST PD. We have developed a new approach to modelling KC data & have applied it to describing the PD of GF vs. ST. Log-phase cultures (107–8 CFU/mL) of ST (MIC=0.5 mg/L) were exposed to GF at 0, 0.5, 1, 2, 4 & 8xMIC; bacterial counts (CFU) were measured serially over 24h. Timecourse of CFU were fit to a PD model with capacity-limited bacterial growth, 1st-order rate constant for death (Kd) & a Hill-type function in which GF enhances Kd. The total CFU was represented by a mixture model, with up to 4 sub-populations (SP) differing in GF susceptibility. Each KC was fit individually & later simultaneously, using Adapt II. AIC was used to determine the number of SP & which parameters would be allowed to vary between KC. The final model had inter-KC variance in maximum velocity of growth & 4 SP. The 1st 2 SP were 99.99% of the initial CFU with sensitivities <1xMIC & the other 2 SP were each <0.01% of total CFU, with sensitivities of 2.3 & 4.4xMIC. The GF Emax was a 37-fold increase in Kd. Goodness of fit was excellent with an overall r=0.96 (Observed=1.01Fit−0.15). This approach to PD modelling of in vitro data will give better insight into the activity of GF vs. different ST SP & aid in determining regimens which minimize therapeutic failure due to the development of resistance. Clinical Pharmacology & Therapeutics (2004) 75, P42–P42; doi: 10.1016/j.clpt.2003.11.159
Interactions among ethanol, hypothermia, and asphyxia in guinea pigs

Summary In newborn and adult guinea pigs, both ethanol and hypothermia were found to postpone the time of last gasp during asphyxia. Hypothermia provided greater protection against asphyxia than did ethanol, and when both were combined there were markedly greater benefits than when either was used alone. All recorded responses to asphyxia (time at which gasping was initiated, gasping interval, gasping rate, and total gasps) suggested that the observed benefits derive from generalized slowing of the rate of deterioration of the condition of the animals. Recovery experiments demonstrated that ethanol not only postponed the time of last gasp but also lengthened the time during which spontaneous recovery from asphyxia is possible.
The generalized matrix continued-fraction descriptions and their application to model simplification†

This paper presents two generalized matrix continued-fraction descriptions in the second Cauer form from a transfer function matrix and/or matrix fraction descriptions which may contain non-square and/or non-regular polynomial matrices. It also presents two model reduction techniques for model simplification of high-degree non-square transfer function matrices and matrix fraction descriptions. The expansion algorithms as well as the inversion algorithms for the generalized matrix continued-fraction descriptions are derived. Two model reduction techniques, which are the matrix continued-fraction expansion method and the mixed method of the matrix continued-fraction expansion method and the equivalent-dominant pole method, are developed for model simplification of multivariable control systems.
Operations Analysis of the 2nd Generation Reusable Launch Vehicle

The Space Launch Initiative (SLI) program is developing a second-generation reusable launch vehicle. The program goals include lowering the risk of loss of crew to 1 in 10,000 and reducing annual operations cost to one third of the cost of the Space Shuttle. The SLI missions include NASA, military and commercial satellite launches and crew and cargo launches to the space station. The SLI operations analyses provide an assessment of the operational support and infrastructure needed to operate candidate system architectures. Measures of the operability are estimated (i.e. system dependability, responsiveness, and efficiency). Operations analysis is used to determine the impact of specific technologies on operations. A conceptual path to reducing annual operations costs by two thirds is based on key design characteristics, such as reusability, and improved processes lowering labor costs. New operations risks can be expected to emerge. They can be mitigated with effective risk management with careful identification, assignment, tracking, and closure. SLI design characteristics such as nearly full reusability, high reliability, advanced automation, and lowered maintenance and servicing coupled with improved processes are contributors to operability and large operating cost reductions.
PCR Amplification of Wheat Sequences from DNA Extracted During Milling and Baking

ABSTRACT DNA-based analyses are highly sensitive and specific. Because processing steps can have profound effects on the proteins and DNA present in foods, this project examined the effects of breadmaking on wheat DNA size and polymerase chain reaction (PCR)-based detection of sequences. DNA was extracted from wheat kernels, milling fractions, and flour, and from samples taken at various steps during and after the baking process. Kernels contained primarily high molecular weight DNA (>12,000 base pairs [bp]), whereas flour DNA exhibited a broad range of molecular weights from >12,000 bp to <300 bp. A marked reduction in DNA yield and size occurred after the first 5 min of baking. PCR successfully amplified products of both high and low copy number genes, even from DNA extracted from bread loaves five days after baking. However, successful amplification required that the maximum product size be no more than the average molecular weight of the DNA recovered from the source. The data also demonstrate that PC...
Time-space transformations of geographic space for exploring, analyzing and visualizing transportation systems

Transportation systems exist within at least two types of space. One is the apparent geographic space, but equally important is the time–space implied by the travel time relations created by the system. Differences between the geographic and time–spaces are properties induced by the transportation system. Methods for time–space transformations of geographic space to explore, visualize and analyze transportation systems were initially developed in the 1960s and 1970s. However, these methods have not been pursued beyond this initial flurry of research activity, most likely due to the difficulties associated with handling and processing digital geographic data. The rise of geographic information systems (GIS), as well as continued development and wider availability of transformation techniques such as multidimensional scaling (MDS) and spatial analytical techniques such as bidimensional regression can allow the potential of time–space transformation techniques to be realized. This paper presents a general methodological framework that exploits recent advances in GIS, MDS and spatial analytical techniques. Results from applying these techniques to the Salt Lake City metropolitan area illustrate the power of these techniques to reveal spatial patterns in the travel time relationships induced by a transportation system. The application also addresses fundamental issues in time–space transformations, such as two-dimensional versus three-dimensional solutions, Euclidean versus non-Euclidean solutions and symmetric and asymmetric solutions.
Developments toward a complete micro-total analysis system for Duchenne muscular dystrophy diagnosis

Abstract The diagnosis of Duchenne muscular dystrophy (DMD) has historically utilized either PCR or requires Southern blot analysis, a southern blot analysis, however, is not amenable to incorporation in a microdevice format. A PCR amplification-based method has been developed, and we have previously coupled this amplification with microchip separation of the PCR fragments for DMD diagnosis. Diagnoses of affected patients were performed by comparing exon concentrations to those of control samples amplified at the same time. To accurately identify mutations in patient samples, this work established normal ranges for the concentration of each amplified exon fragment using control samples amplified over successive days. Our studies show that the number of cycles used in the amplification process affects this range. Affected patient samples were analyzed using these normal ranges and the mutations detected by Southern blot analysis were also diagnosed using the microchip separation method. Employing the microchip separation method decreases the time required for the analysis, but the time required for DNA purification and PCR amplification must also be decreased for faster total analysis of patient samples. Development of microchip methods for these processing steps is one approach for reducing the individual times, while also providing the possibility of integrating these steps in a single device. Here we report on the microchip extraction of genomic DNA from whole blood using a novel sol–gel matrix that is easily formed in microdevices. IR-mediated PCR amplification of a β-globin fragment from genomic DNA followed by electrophoretic analysis on a single integrated microdevice is presented for the first time. Work towards the development of a micro-total analysis device for DMD diagnosis, through integration of all processing steps on a single device, is also discussed.
Detecting small quantities of DNA on CsCl gradients

Abstract The fluorescent assay of Kissane and Robbins can be applied to detect low levels of DNA in CsCl gradients and is capable of resolving buoyant density distribution patterns from gradients containing as little as 2–4 μg of DNA.
The $ηNN$ coupling constant

We derive the light cone QCD sum rule for the $\eta NN$ coupling constant $g_{\eta NN} $. The contribution from the excited states and the continuum is subtracted cleanly through the double Borel transform with respect to the two external momenta, $p_1^2$, $p_2^2=(p-q)^2$. Our result is $\alpha_{\eta NN}=(0.3\pm 0.15)$, which favors small values used in literatures.
Effect of cimetidine on plasma lipids and lipoproteins

The effect of oral cimetidine on plasma lipid and lipoprotein levels was evaluated in a double-blind crossover study in 12 normal subjects and in 12 subjects with fasting serum glucose levels ≥ 140 mg% or levels after a 100-gm oral glucose dose ≥ 170 mg%. Plasma cholesterol (total, high-density, low-density, and very low-density lipoprotein) and triglyceride (total and very low-density lipoprotein) concentrations in placebo and cimetidine periods did not differ. Cimetidine was associated with elevated serum creatinine and aspartate amino transferase (SGOT) levels. One subject was impotent while on cimetidine. Clinical Pharmacology and Therapeutics (1984) 36, 217–220; doi:10.1038/clpt.1984.165
Broadening of short light pulses by many reflections from multilayer dielectric coatings.

The broadening of short light pulses which are reflected from multilayer dielectric mirror coatings is calculated. The case when a pulse is reflected many times is treated in detail. The quarter-wave stack is the design for minimal pulse broadening. The broadening after many reflections is mainly due to the phase variations close to the edge of the reflection band of the coating. The shortest output pulses are obtained if only the center part of the reflection band of the mirror is used; an input pulse which contains only this part of the spectrum produces a much shorter output pulse than a δ-function input. Output pulses as short as 10−13 see are possible for typical mirror coatings and one-thousand reflections. The influence of errors in the fabrication of a coating on the calculated results is discussed.
An RNA motif that binds ATP

RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.
Peripheral dose to the testes: the design and clinical use of a practical and effective gonadal shield☆

A simple and practical gonadal shield has been developed for use near megavoltage radiation fields. The lead shield encloses only the testes, allowing its use with nearly any radiation field that does not include the testes. The dose to the testes with and without the shield has been measured extensively both in phantoms and on patients. The gonadal shield allows a 3 to 10-fold reduction in dose to the testes depending primarily on the distance from the field edge to the gonads. When the shield is used, the gonadal dose is always less than 1% of the patient's prescription dose. Based on our patient studies of testicular injury following conventionally-fractionated irradiation, a dose of less than 50 cGy (1% of a typical 5000 cGy treatment regimen) should preserve normal testicular function.
Origins of Stability in Mixed Bismuth−Indium Clusters†

The electronic structure and stability of neutral and negatively charged BixIny (x = 1−4, y = 1−6) clusters are investigated through anionic photoelectron spectroscopy employing magnetic bottle and photoelectron velocity map imaging experiments. Experimental and theoretical adiabatic and vertical detachment energies of the anionic species containing up to 4 Bi and 4 In atoms are deduced from first principles calculations. Among the BixIny series, many clusters are found to exhibit special stability in the mass spectra, exhibit a large gap between the highest occupied and lowest unoccupied molecular orbitals (HOMO−LUMO gap), and a large formation energy. This stability is rationalized by different mechanisms. Bi2In− is classified as a gas phase Zintl species despite only having three atoms, making it the smallest possible case. Bi3In2−, with 12 valence electrons and a closo structure in agreement with Wade’s rule, is similar to Bi3Ga2−, a gas phase Zintl analogue of Sn52−. Bi4In− and Bi4In2 are both found ...