cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparison of nitrate reductase mutants of Escherichia coli selected by alternative procedures.

Seventy-two mutants deficient in formate-nitrate reductase activity were selected in Escherichia coli strain PK 27, by two different procedures. Forty-five strains were selected on the basis of chlorate resistance and 27 strains were selected by their inability to reduce nitrate with formate as an electron donor. Genetic analysis of these strains showed that the two techniques yield distinctly different distributions of mutants among the various controlling genetic loci. Chlorate resistance appears to select for severe alterations in the nitrate reductase system; 98% of these mutants fell into the pleiotropic chl A, B, D and E classes and are deficient in all the activities of the formate-hydrogenlyase pathway as well as formate-nitrate reductase pathway. In contrast, 48% of the mutants selected for their inability to reduce nitrate with formate as the electron donor were of the chl C class and two new classes were identified among mutants selected by this procedure. Chl F mutants are linked to tryptophan and the chl C locus. Chl G mutants map at zero minutes on the E. coli genetic map.
High-throughput single-nucleotide structural mapping by capillary automated footprinting analysis

The use of capillary electrophoresis with fluorescently labeled nucleic acids revolutionized DNA sequencing, effectively fueling the genomic revolution. We present an application of this technology for the high-throughput structural analysis of nucleic acids by chemical and enzymatic mapping (‘footprinting’). We achieve the throughput and data quality necessary for genomic-scale structural analysis by combining fluorophore labeling of nucleic acids with novel quantitation algorithms. We implemented these algorithms in the CAFA (capillary automated footprinting analysis) open-source software that is downloadable gratis from https://simtk.org/home/cafa. The accuracy, throughput and reproducibility of CAFA analysis are demonstrated using hydroxyl radical footprinting of RNA. The versatility of CAFA is illustrated by dimethyl sulfate mapping of RNA secondary structure and DNase I mapping of a protein binding to a specific sequence of DNA. Our experimental and computational approach facilitates the acquisition of high-throughput chemical probing data for solution structural analysis of nucleic acids.
Nicotine exposure and the risk of SIDS

The effects of parental smoking and nicotine exposure link a number of seemingly independent observations in SIDS research. There is accumulating evidence that fetal development and wellbeing are closely related to the subsequent risk of SIDS in the offspring. Furthermore, it appears that this risk is related, in particular, to alterations in brain development. The risk of dying of SIDS may thus, in reality, be confined to a limited number of infants with developmental changes in CNS function. Our findings of age-specific attenuation of hypoxic defense following nicotine exposure focus the attention on brain catecholamine metabolism as a potential target for adverse fetal and neonatal influences. To clarify the mechanisms of nicotine exposure on postnatal development of the control of respiration and cardiovascular control may thus offer insights into the ultimate mechanism of SIDS.
Estimating lightning channel characteristics of positive narrow bipolar events using intrachannel current reflection signatures

[1] A set of 133 positive narrow bipolar lightning events located by the Los Alamos Sferic Array (LASA) is examined. The events were selected because their fast electric field change (EFC) records show a secondary positive peak, following the primary positive peak, which is consistent with what would be expected for a propagating current pulse reflecting off an impedance discontinuity along a transmission line. With an assumed propagation speed, the time difference between the primary and secondary (reflected) peak in the field change record offers a direct technique for estimating the length of the discharge channel. If the signal amplitude is assumed to decay exponentially with time and that the reflection coefficient is near unity, the time difference between peaks and the ratio of their amplitudes yields an estimate of the temporal decay rate constant. Statistics on the 133 located events examined show an average peak-to-reflected-peak time of 6.7 μs, a mean amplitude ratio estimate of 6.1, and an amplitude decay rate constant of 4.0 μs. Bound by the speed of light, the upper limit on channel length for the typical positive narrow bipolar event (NBE) in this study is shown to be approximately 2 km.
Spinal accessory nerve palsy: An unusual complication of rhytidectomy

Rhytidectomy is a safe and effective procedure for rejuvenation of the aging face. Reported complication rates vary between 2.5% and 28%, and with proper management, longterm sequelae are unusual. Injury to the spinal accessory nerve is a rare but potentially debilitating complication of rhytidectomy. Afflicted patients present with dull, constant pain in the shoulder region which can be severe in nature. In addition, there is weakness of shoulder abduction and cosmetic deformity related to trapezius atrophy. Measures for conservative management include analgesics and physical therapy to strengthen the shoulder girdle. Nerve exploration is indicated for cases with documented denervation that do not respond to conservative treatment. A review of the English literature identified two previous case reports of spinal accessory nerve injury sustained during rhytidectomy. In this report, we present two additional cases and review current concepts regarding diagnosis, management, and prevention of this unusual complication of rhytidectomy. © 1994 John Wiley & Sons, Inc.
Evidence for the presence of mutagenic compounds other than chromium in particles from mild steel welding.

Abstract A modified Salmonella/microsome liquid culture assay was used to investigate the mutagenicity of the particulate fraction from mild steel welding. Previous reports have implicated compounds of chromium VI as the mutagenic and toxic agents in welding fumes, since only the particles from welding on stainless steel, which contains 15–25% chromium, were mutagenic, whereas particles from welding on mild steel, which contain less than 0.1% chromium, were not mutagenic or toxic. In this investigation, mild steel particles were shown to contain direct-acting and promutagenic compounds that induced frameshift mutations. The mutagenic agents, which were insoluble in sodium phosphate buffer, did not include chromium VI or organin compounds. Further, the expression of mutatino appears to require a cell-particle interaction for the release of the mutagenic species from the particles.
Kinetics of Liquid Spreading and Penetration with Application to RuO2−Glass Thick-Film Resistors

The rate of spreading of a spherical liquid droplet on a flat substrate is analyzed using the time-dependent contact angle approach. The constants in the contact angle development equation are explicitly related to physical parameters. Normalized rate of spreading is shown to be independent of the volume of the liquid droplet. A general capillary flow equation incorporating the time-dependent contact angle is used to analyze the kinetics of infiltration of the glass phase into the conductive phase in RuO2/lead-horosilicate-glass thick-film resistors. The dependence of the kinetics on temperature, interparticle separation, and dissolved alumina content of the glass are discussed with reference to microstructure development in these resistors.
A ROLE FOR HSP90 IN RETINOID RECEPTOR SIGNAL TRANSDUCTION

The ubiquitous heat shock protein Hsp90 appears to participate directly in the function of a broad range of cellular signal transduction components, including steroid hormone receptors; however, an evolutionarily related subclass of intracellular receptors, exemplified by the retinoid receptors RAR and RXR, had been inferred from biochemical studies to function independently of Hsp90. To examine this issue genetically, we measured mammalian and avian retinoid receptor activity in a Saccharomyces cerevisiae strain in which the expression of the yeast Hsp90 homologue could be conditionally repressed approximately 20-fold relative to wild type. We tested transcriptional activation by RAR or RXR-RAR, from two types of retinoic acid response elements, triggered by three different agonist ligands. In every condition, we found that activation was severely compromised under conditions of low Hsp90 expression. We showed that the defect was in signal transduction rather than transcription activation per se, and that high affinity hormone binding was abolished in extracts of cells producing low levels of Hsp90. We suggest that Hsp90 may function in at least one step of signal transduction by all members of the intracellular receptor superfamily.
A Bayesian approach to the inference of diploid genotypes using haploid genotypes

Morris and Spieth (1978) described a method of calculating unbiased estimates of diploid genotype frequencies given information on the genotypes of haploid cells derived from diploid individuals. They concluded that three haploids per diploid would minimize sampling variance of genotype frequencies, given a fixed total number of haploids examined. If the identity of individual diploid genotypes is needed, Morris and Spieth (1978) stated that more haploids should be collected per diploid. We extend this work by showing from a Bayesian perspective that the probability of misclassification of individuals depends not only on the number of haploids sampled, but also on the genetic structure of the population since misclassification error will increase as the frequency of heterozygotes increases. Since information on the genetic structure (allele frequencies, inbreeding coefficient) of a population is rarely known prior to the initiation of an empirical study, the usefulness of our Bayesian approach is in experimental design, by revealing the magnitude of possible misclassification errors given a particular choice of number of haploids.
Labeling and Purification of Cellulose-Binding Proteins for High Resolution Fluorescence Applications

The study of enzymatic reactions through fluorescence spectroscopy requires the use of bright, functional fluorescent molecules. In the case of proteins, labeling with fluorescent dyes has been carried out through covalent reactions with specific amino acids. However, these reactions are probabilistic and can yield mixtures of unlabeled and labeled enzymes with catalytic activities that can be modified by the addition of fluorophores. To have meaningful interpretations of results from the study of labeled enzymes, it is then necessary to reduce the variability in physical, chemical, and biological characteristics of the labeled products. In this paper, a solid phase labeling protocol is described as an advantageous alternative to free solution labeling of cellulose-binding proteins and is applied to tag cellulases with three different fluorophores. The products from the labeling reactions were purified to remove the unreacted dye and separate labeled and unlabeled enzymes. Characterization of the catalyti...
Immunization strategies to augment oral vaccination with DNA and viral vectors expressing HIV envelope glycoprotein.

Abstract Induction of mucosal immunity to the human immunodeficiency virus (HIV) envelope (env; gp160) glycoprotein has been demonstrated with orally administered recombinant vaccinia virus (rVV) vectors and poly( dl -lactide-co-glycolide) (PLG)-encapsulated plasmid DNA expressing gp160. In this study, we investigated the effect of an oral DNA-prime/rVV-boost vaccine regimen in conjunction with adjuvants on the level of gp160-specific cellular and humoral responses in BALB/c mice. We demonstrated that DNA priming followed by a booster with rVV expressing gp160 (vPE16) significantly augmented env-specific immunity in systemic and mucosal tissues of the immunized mice. Association of vPE16 with liposomes and coadministration of liposome-associated β-glucan lentinan or IL-2/Ig-encoded plasmid DNA-encapsulated in PLG microparticles triggered the optimal cell-mediated immune (CMI) responses. Lentinan was found to increase env-specific type 1 cytokine production and cytotoxic T-lymphocyte (CTL) activities but had no effect on humoral responses. On the other hand, IL-2/Ig-mediated increases in both type 1 and 2 activities were associated with higher levels of env-specific CTL and antibody responses. Results of these studies demonstrated the effectiveness of oral vaccines with DNA and rVV vectors in conjunction with immunomodulators in inducing specific immune responses in systemic and mucosal tissues.
The reorganization of the information systems of the US naval construction forces: an action research project

Organization change is a difficult task under the best of circumstances. Change dictated from outside the organization makes a reorganization project even more difficult. This study follows the information systems reorganization of the US Naval Construction Forces whose restructuring was directed as a result of budget cuts and military ‘right-sizing’. The process was conducted through the use of action research, an intensive investigative method seeing limited use in information system's research. This method directly involves the researcher in the organizational change effort while placing organization members in close collaboration with the researcher. The study describes the action research methodology while illustrating the research strategy in phases and recounts the successful migration from a highly centralised to a decentralised organization.
The intensity variation of the atomic oxygen red line during morning and evening twilight on 9-10 April 1969

Abstract During the evening of 9 April and the morning of 10 April 1969, the twilight zenith intensity of the atomic oxygen red line OI(3P-1D) at 6300 A was measured at the Blue Hill Observatory (42°N, 17°W). At the same time incoherent scatter radar data were being obtained at the Millstone Hill radar site 50 km distant. We have used a diurnal model of the mid-latitude F-region to calculate the ionospheric structure over Millstone Hill conditions similar to 9–10 April 1969. The measured electron temperature, ion temperature, and electron density at 800 km are used as boundary conditions for the model calculations. The diurnal variation of neutral composition and temperature were obtained from the OGO-6 empirical model and the neutral winds were derived from a semiempirical three-dimensional dynamic model of the neutral thermosphere. The solar EUV flux was adjusted to yield reasonable agreement between the calculated and observed ionospheric properties. This paper presents the results of these model computations and calculations of the red line intensity. The 6300 A emission includes contributions from photoelectron excitation, dissociative recombination, Schumann-Runge photodissociation and thermal electron impact. The variations of these four components for morning and evening twilight between 90–120° solar zenith angles, and their relative contributions to the total 6300 A emission line intensity, are presented and the total is compared to the observations. For this particular day the Schumann-Runge photodissociation component, calculated using the solar fluxes tabulated by Ackermann (1970), is the dominant component of the morning twilight 6300 A emission. During evening twilight it is necessary to utilize a lower O2 density than for the morning twilight in order to bring the calculated and observed 6300 A emission rates into agreement. The implication that there may be a diurnal variation in the O2 density at the base of the thermosphere is discussed in the light of available experimental data and current theoretical ideas.
A high resolution far infrared study of rotation in HN3, HNCO, HNCS, and their deuterium derivatives

Abstract The pure rotational spectra of HN3, HNCO, HNCS and their deuterium derivatives have been obtained in the spectral range 20–250 cm−1 with spectral slit widths of 0.2–0.5 cm−1. Both the widely spaced RQK branches (ΔK = + 1) and their associated RRK and RPK branches were observed. For HN3 the Q branches can be fitted reasonably well by first-order distortion theory, but higher-order treatment is required for HNCO and HNCS because of the unprecedentedly large centrifugal distortion. Analysis of the data yields the following values of the rotational constants A 0 - B 0 , B 0 and DK respectively, all in cm−1; HN3, 19.94 ± 0.03, 0.3967 ± 0.0002, (0.766 ± 0.002) × 10−2; HNCO, 30.22 ± 0.1, 0.3664 ± 0.0002, 0.17 ± 0.01; HNCS, 44.70 ± 0.1, 0.1950 ± 0.001, 1.20 ± 0.1. The very large values of DK for HNCO and HNCS have significance only when taken along with terms involving K up to K10.
ERBBs in the gastrointestinal tract: Recent progress and new perspectives

The gastrointestinal epithelium does much more than provide a physical barrier between the intestinal lumen and our internal milieu. It is actively engaged in absorption and secretion of salt and water via ion transporters, exchangers and selective ion channels. It is also a continuously self-renewing epithelium that undergoes ordered growth and differentiation along its vertical axis. From this dual perspective, we will consider the actions of the ERBB family of ligands and receptors in the maintenance of gastrointestinal homeostasis and discuss instances when the actions of this family go awry such as in cancer and Menetrier's disease.
Nonstationary behavior of collisionless shocks

Laboratory measurements indicate that a collisionless shock wave formed in a plasma-wind-tunnel device is nonstationary on the time scale of the ion gyroperiod. This behavior suggests a possible interpretation of recent data on magnetic field structure in the vicinity of Earth's bow shock. Comparison is made between the laboratory measurements and earlier computer simulations in which ion gyromotion was included.
Redkino to Rutland--a glimmer of Glasnost.

Margaret Herd met Vladimir Nikitin on a BDJ study tour in the Soviet Union in March 1988. As a result of their meeting Margaret moved heaven and earth to help Vladimir come for a taste of the West. He spent a month in Britain last Christmas, encountering with awe and disbelief the many everyday things that we take for granted. Here Margaret describes Vladimir's brief visit
Conjugate duality in generalized fractional programming

The concepts of conjugate duality are used to establish dual programs for a class of generalized nonlinear fractional programs. It is now known that, under certain restrictions, a symmetric duality exists for generalized linear fractional programs. In this paper, we establish this symmetric duality for the nonlinear case.
Impedance cardiography: the next vital sign technology?

Objective To evaluate the following: (1) the intramethod variability of impedance cardiography (ICG) cardiac output (CO) measurements via the latest generation monitor and thermodilution CO measurements (CO-TDs); (2) the intermethod comparison of ICG CO and CO-TD; and (3) comparisons of the intergeneration ICG CO equation to CO-TD, using the latest ICG CO equation, the ZMARC (CO-ICG), and the predecessor equations for measuring the ICG CO of Kubicek (CO-K), Sramek (CO-S), and Sramek-Bernstein (CO-SB). Design Prospective study. Setting A cardiovascular-thoracic surgery ICU in a community university-affiliated hospital. Patients Post-coronary artery bypass graft patients (n = 53) in whom 210 pairs of CO measurements were made. Interventions None. Measurements and main results The CO-ICG was determined simultaneously while the nurse was performing the CO-TD. Variability within the monitoring method was better for CO-ICG compared to CO-TD (6.3% vs 24.7%, respectively). The correlation, bias, and precision of the CO-ICG was good compared to CO-TD ( r 2 = 0.658; r = 0.811; bias, −0.17 L/min; precision, 1.09 L/min; CO-ICG = 1.00 × CO-TD − 0.17; p r 2 = 0.309; r = 0.556; bias, −1.71 L/min; precision, 1.81 L/min; CO-K = 0.78 × CO-TD − 0.45; p r 2 = 0.361; r = 0.601; bias, −1.46 L/min; precision, 1.63 L/min; CO-S = 0.80 × CO-TD − 0.36; p r 2 = 0.469; r = 0.685; bias, −0.77 L/min; precision, 1.69 L/min; CO-SB = 1.03 × CO-TD − 0.95; p Conclusion The latest ICG technology for determining CO (CO-ICG) is less variable and more reproducible in an intrapatient sense than is CO-TD, it is equivalent to the average accepted CO-TD in post-coronary artery bypass graft patients, and showed marked improvement in agreement with CO-TD compared to measurements made using previous generation ICG CO equations.
The Mechanism of Action of Rubefacients

Investigations of the physiological action and therapeutic effect of rubefacients have been relatively few, and the reports have been somewhat contradictory. From the historical point of view, the present concept of the axon reflex is based upon the observation by microscopy of vasodilation in response to irritant oils and the abolition of this effect by cocaine (1). However, the relative effectiveness of such substances for producing an increase in blood flow has been disputed (2). Taylor (3) measured the temperatures of subcutaneous tissue and muscle in dogs in a study of possible counterirritant action of croton oil, mustard oil and turpentine, but reported only slight increases interpreted as interference with radiation of heat by the gauze covering the experimental skin site. On the other hand, Lange and Winer (4) reported significant elevations in skin temperature after applying certain proprietary preparations especially those containing mustard oil.
Effect of dietary cadmium on calcium metabolism in the rat during late gestation.

Sprague--Dawley rats were given access to water containing control, 10, 25 ppM Cd beginning on day 0 of gestation. On day 21 of gestation, fetal and maternal tissues were collected from dams which had been dosed 24 hr previously with 16 ..mu..Ci of /sup 45/CaCl/sub 2/. Maternal and fetal hematocrits decreased, indicating a possible interference with iron metabolism. No changes in total or radiocalcium found in fetal body were detected as a function of Cd treatment. Fetal bone stable and radiocalcium increased by as much as 33% at 25 ppM while fetal liver and kidney stable Ca decreased compared to controls. It is evident that low Cd exposures lead to changes in fetal Ca metabolism rather than causing changes in the amount of Ca transported across the placenta.
Mother-child participation in conversation about the past: relationships to preschoolers' theory of mind.

Forty 3.5- to 4.5-year-olds discussed 3 past events with their mothers and completed a set of theory of mind tasks indexing their ability to reason about conflicting mental representations and their understanding of knowledge. Semipartial correlations and analyses of covariance showed that children's theory of mind scores were related to their participation in memory conversations, independent of age and linguistic skill. The frequency with which mothers provided new information was related to children's theory of mind scores, although mothers' direct replies to children were generally unrelated to children's understanding of mind. This research takes an important step toward examining the relevance of theory of mind skills to real-world, social interaction. The results have implications for explaining the emergence of autobiographical memory.
Manganese modulation of MAPK pathways: effects on upstream mitogen activated protein kinase kinases and mitogen activated kinase phosphatase-1 in microglial cells.

Multiple studies demonstrate that manganese (Mn) exposure potentiates inflammatory mediator output from activated glia; this increased output is associated with enhanced mitogen activated protein kinase (MAPK: p38, ERK, and JNK) activity. We hypothesized that Mn activates MAPK by activating the kinases upstream of MAPK, i.e., MKK-3/6, MKK-1/2, and MKK-4 (responsible for activation of p38, ERK, and JNK, respectively), and/or by inhibiting a major phosphatase responsible for MAPK inactivation, MKP-1. Exposure of N9 microglia to Mn (250μM), LPS (100 ng/ml), or Mn+LPS increased MKK-3/6 and MKK-4 activity at 1 h; the effect of Mn+LPS on MKK-4 activation was greater than the rest. At 4 h, Mn, LPS, and Mn+LPS increased MKK-3/6 and MKK-1/2 phosphorylation, whereas MKK-4 was activated only by Mn and Mn+LPS. Besides activating MKK-4 via Ser257/Thr261 phosphorylation, Mn (4 h) prevented MKK-4’s phosphorylation on Ser80, which negatively regulates MKK-4 activity. Exposure to Mn or Mn+LPS (1 h) decreased both mRNA and protein expression of MKP-1, the negative MAPK regulator. In addition, we observed that at 4 h, but not at 1 h, a time point coinciding with increased MAPK activity, Mn+LPS markedly increased TNF-α , IL-6, and Cox-2 mRNA, suggesting a delayed effect. The fact that all three major groups of MKKs, MKK-1/2, MKK-3/6, and MKK-4 are activated by Mn suggests that Mn-induced activation of MAPK occurs via traditional mechanisms, which perhaps involve the MAPKs farthest upstream, MKKKs (MAP3Ks). In addition, for all MKKs, Mn-induced activation was persistent at least for 4 h, indicating a long-term effect.
Alcohol and Women: What is the Role of Biologic Factors?

Biological factors influence almost every factor that contributes to alcohol consumption: its metabolism by the liver, its neurochemical effects in the brain, and its activation of complex processes like reinforcement and aversion. This article summarizes how these biological factors contribute to alcohol consumption by women.
Dissolution Studies of Human Enamel Treated with Aluminum Solutions

Dissolution tests using human enamel were conducted after treatment with aqueous solutions of various aluminum (Al) salts. All Al compounds, except those which formed stable Al-complexes, greatly decreased enamel dissolution in a pH 4 acetate buffer. A comparison with fluoride compounds demonstrated that Al was equivalent to SnF2 and more effective than NaF and Na2PO3F. Furthermore, the reduction in enamel dissolution produced by Al persisted after more than three hr of successive demineralization, which was twice as long as that observed with a pH 4.5 SnF2 solution.
Gene therapy in wound healing

Gene therapy is a new and emerging technology that has been catalyzed by the progress of the Human Genome Project. It employs the process of manipulating genes to achieve a clinically beneficial alteration in gene product. Wound healing lends itself to the application of gene therapy by virtue of the vast array of proteins involved in its complex cascade. This article provides an overview of the background to gene therapy and describes current techniques in use as applied to wound healing. The authors show the potential role that many candidate genes may offer in the future for optimizing wound healing through gene therapy.
Transmission Time and Bandwidth in Pulse Code Modulation (Application of the Statistical Thermodynamic Formalism)

Employing the “statistical thermodynamic formalism” developed in an earlier paper, it is possible to determine “compact” sets of transmission times for the words of PCM (pulse code modulation) messages. In particular, we deal with pulses of zero or unit heights. These compact signals, which lead to shorter message times and eliminate redundancy even when successive words are correlated (Markov source), may, however, require additional bandwidth. We examine two simple cases where autocorrelation functions, and therefore power spectra, can be evaluated. In one case, that of the Markov source, it proves possible to accomplishboth shorter transmission time and narrower bandwidth (half-width of the power spectrum), showing that optimization of transmission times can be very worthwhile. Techniques for deriving autocorrelation functions are discussed at length.
Phase contrast photomicrography of cellular behaviour in spongillid porocytes (Porifera: Spongillidae)

The combination of phase contrast photomicrography with a method for phase contrast observation of living sponges facilitated the initial photographic record of spongillid porocyte cellular behavior. Porocytes ofCorvomeyenia carolinensis Harrison (Spongillidae) exhibit true intracellular pores and are components of the incurrent system. The number of porocyte contractile vacuoles increases during pore dilation. This increase is possibly related to an increase in the amount of cell surface in contact with the hypotonic aqueous environment. The porocyte cell type appears closely related to, and is likely derived morphogenetically from, pinacocytes of the upper pinacoderm.
The molecular structure of firefly D-(-)-luciferin: a single crystal x-ray analysis.

Abstract Crystals of luciferin in space group P2 1 2 1 2 1 gave cell parameters of a = 9.248, b = 22.970, c = 5.331 A, D C = 1.644 gm/cm 3 with 4 molecules per unit cell. The structure and absolute configuration were confirmed to be identical to that established by chemical procedures. Resonance effects of the 6′-phenolic group are distinctly evident. The rings are oriented with the NCCN system trans planar. The carboxyl and thiazoline sulfur are positioned to the same side of the thiazoline ring. The non-bonded intramolecular contacts are normal.
The Importance of Legislative Reform of the Fda

AbstractThe US Food and Drug Administration (FDA) has raised the regulatory burden on drug companies by continually introducing new requirements and policies, regardless of their potential to hinder the delivery of new and innovative therapies to patients who need them. the drug development system in the United States has become the slowest and most expensive in the world. In a climate of deregulation, FDA has sought to cultivate the image of an agency reforming itself from within—lessening the burden on regulated industry and lowering review times—but such “improvements” are largely illusory. FDA has shown itselfincapable of reforming itself, and only carefully crafted legislation will significantly improve the oversight of drug development.
Integration of coastal inundation modeling from storm tides to individual waves

Abstract Modeling of storm-induced coastal inundation has primarily focused on the surge generated by atmospheric pressure and surface winds with phase-averaged effects of the waves as setup. Through an interoperable model package, we investigate the role of phase-resolving wave processes in simulation of coastal flood hazards. A spectral ocean wave model describes generation and propagation of storm waves from deep to intermediate water, while a non-hydrostatic storm-tide model has the option to couple with a spectral coastal wave model for computation of phase-averaged processes in a near-shore region. The ocean wave and storm-tide models can alternatively provide the wave spectrum and the surface elevation as the boundary and initial conditions for a nested Boussinesq model. Additional surface-gradient terms in the Boussinesq equations maintain the quasi-steady, non-uniform storm tide for modeling of phase-resolving surf and swash-zone processes as well as combined tide, surge, and wave inundation. The two nesting schemes are demonstrated through a case study of Hurricane Iniki, which made landfall on the Hawaiian Island of Kauai in 1992. With input from a parametric hurricane model and global reanalysis and tidal datasets, the two approaches produce comparable significant wave heights and phase-averaged surface elevations in the surf zone. The nesting of the Boussinesq model provides a seamless approach to augment the inundation due to the individual waves in matching the recorded debris line along the coast.
Dynamic loading on impact surfaces of a high subsonic elliptic jet

The feedback resonance in a high subsonic velocity range was investigated for the case where a small aspect ratio (2:1) elliptic jet impinged perpendicularly on a flat plate. This resonance was observed for Mach numbers greater than 0.7 for plate locations between 4 and 9 major radii downstream of the exhaust plane. At the predominant resonant conditions, the loading region and sound source terms were found to be concentrated along the major axis direction on the impact surface.
Psychophysical Dissection of Genotype Effects on Human Bitter Perception

The purpose of this study was to define the effects of individual polymorphisms within the haplotypes of the TAS2R38 taste receptor gene on human bitter taste perception. A racially and ethnically diverse sample of children and adults (N = 980) was phenotyped for thresholds of 6-n-propylthiouracil (PROP) and genotyped for 3 polymorphisms of the TAS2R38 gene (A49P, V262A, I296V). Subjects were grouped according to their diplotype (i.e., specific combinations of haplotypes) and compared for PROP thresholds. By contrasting subjects with particular diplotypes, we found that in addition to A49P, V262A and I296V were related to the ability of the subjects to detect PROP. The V262A variant site affected the ability of subjects to detect mid-range concentrations of PROP, whereas the I296V variant site affected the ability of subjects to perceive PROP at the lowest concentration. These data agree with results from previous studies using cell-based assays for 2 variant sites (A49P and V262A) but not those for the I296V variant site. The reason for the discordant results is not known but it highlights the need for psychophysical as well as cell-based methods to understand the genotype-phenotype relationship for taste receptors. Human PROP sensitivity is determined by the combination of each of these 3 polymorphisms within the TAS2R38 gene.
Stability and capacity of regular wireless networks

We study the stability and capacity problems in regular wireless networks. In the first part of the paper, we provide a general approach to characterizing the capacity region of arbitrary networks, find an outer bound to the capacity region in terms of the transport capacity, and discuss connections between the capacity formulation and the stability of node buffers. In the second part of the paper, we obtain closed-form expressions for the capacity of Manhattan (two-dimensional grid) and ring networks (circular array of nodes). We also find the optimal (i.e., capacity-achieving) medium access and routing policies. Our objective in analyzing regular networks is to provide insights and design guidelines for general networks. The knowledge of the exact capacity enables us to quantify the loss incurred by suboptimal protocols such as slotted ALOHA medium access and random-walk-based routing. Optimal connectivity and the effects of link fading on network capacity are also investigated.
Comparisons of wetland and drainage lake influences on stream dissolved carbon concentrations and yields in a north temperate lake-rich region

Processes occurring at various scales interact to influence the export of organic carbon from watersheds to freshwater ecosystems and eventually the ocean. The goal of this study was to determine if and how differences in wetland extent and presence of lakes influenced dissolved organic carbon (DOC) concentrations and yields in streams. We monitored stream flow, DOC and dissolved inorganic carbon concentrations periodically for 2 years at four sites with forested watersheds, four sites with wetland watersheds, and four sites with wetland watersheds that also contained in-network lakes. As expected, the presence of wetlands resulted in higher DOC concentrations and yields, but the impact of lakes was less clear on the magnitude of DOC concentrations and yields. With respect to temporal dynamics, we found positive relationships between stream flow and DOC concentration (median r2 = 0.89) in streams without upstream lakes. The relationships for forested sites are among the strongest reported in the literature, and suggest a clear shift in hydrologic flowpath from intersecting mineral soils at low flow, to organic soils at high flow. In streams with upstream lakes, the relationship between flow and concentration was non-significant for three of four sites unless time lags with flow were applied to the concentration data, after which the relationship was similar to the non-lake streams (median r2 = 0.95). These findings suggest that lakes buffering temporal patterns in streams by hydrologically delaying pulses of carbon, but provide little support that in-line lakes have a net effect on carbon exports in this region.
Ionospheric signatures of plasmaspheric tails

[1] We make direct comparisons between GPS maps of total electron content (TEC) over the North American continent, Millstone Hill radar observations of storm enhanced density, and low and high-altitude satellite measurements of the perturbation of the outer plasmasphere during the March 31, 2001 geomagnetic storm. We find that storm enhanced density (SED) and plumes of greatly-elevated TEC are associated with the erosion of the outer plasmasphere by strong sub-auroral polarization electric fields. The SED/TEC plumes identified at low altitude map closely onto the magnetospheric determination of the boundaries of the plasmapause and plasmaspheric tail determined by EUV imaging from the IMAGE spacecraft. Characteristics of the SED/TEC plumes/tails for the March 31, 2001 event are: TEC ∼ 100 TECu; F-region sunward velocity ∼1000 m/s; sunward flux ∼5*1024 ions s−1; total transport to dayside magnetopause/merging region (3-hr event) ∼5*1028 ions.
Refractive index detector using Zeeman interferometry

We discuss the theory and error analysis for an ultrasensitive refractive index detector based on the two-frequency Zeeman effect laser. Experimental measurements on gases agree fairly well with predictions. With a 5-cm pathlength, the typical interferometry stability is Δn = 8 × 10−9/h. Resolution is Δn = 1 × 10−9.
Unraveling human natural killer cell deficiency

NK cells are a component of the innate immune system identified in animals as serving an essential role in antiviral immunity. Establishing their role in human health has been challenging, with the most direct insight coming from the study of NK cell-deficient individuals. However, NK cell deficiencies are rare, and more research is needed. In this issue of the JCI, two independent groups of researchers have simultaneously identified the genetic cause of a human NK cell deficiency as mutation in the MCM4 gene, encoding minichromosome maintenance complex component 4. These reports suggest a critical role for the minichromosome maintenance helicase complex in NK cells and NK cell-mediated host defense.
A Comparison of Student Attitudes, Statistical Reasoning, Performance, and Perceptions for Web-Augmented Traditional, Fully Online, and Flipped Sections of a Statistical Literacy Class

Web-augmented traditional lecture, fully online, and flipped sections, all taught by the same instructor with the same course schedule, assignments, and exams in the same semester, were compared wi...
Parameter adaptive control of multivariable systems

Model reference adaptive controllers for multivariable plants are designed using only input and output signals rather than the complete state vector. The design is based on Liapunov's direct method, and the Meyer-Kalman-Yacubovich lemma. State variable filters are employed to avoid differentiating output signals. Augmented error signals are used in deriving stable adaptive control laws which assure that the normally used response error signals approach zero asymptotically.
Competence resource specialization, causal ambiguity, and the creation and decay of competitiveness: the role of marketing strategy in new product performance and shareholder value

Marketing strategists should create, maintain, and arrest the decay of causally ambiguous resource competences that lead to competitiveness and thus performance. However, competence causal ambiguity, which helps create competitiveness, is also implicated in competitiveness decay. In this study we test a model of specialization-competitiveness-performance using primary and secondary data from 169 public respondents/firms, to examine the effects of negative internal barriers to replication and adaptation. These barriers develop due to resource lock-in arising from the same specialization processes that lead to the positive barriers to imitation that deter competitors. Results suggest that commitment to learning can mitigate resource lock-in problems with internal competence causal ambiguity, competence causal ambiguity among competitors appears more essential to competitiveness in more competitive markets, competitiveness positively relates to both shareholder value and new product performance, and an increased differential focus on marketing versus operations in the organization strengthens the positive bridge between organizational competitiveness and shareholder return.
IgG4+ Plasma Cells in Isolated Reactive Lymphadenopathy

In the study published in this issue, Louzao Martinez et al1 investigate the significance of increased IgG4-positive plasma cells in lymph nodes. The accurate interpretation of this finding is important as awareness of IgG4-related disease (IgG4-RD) is growing among both clinicians and pathologists, and in consequence, IgG4-RD is included in the differential diagnosis of an increasing number of specimens. From a historical perspective, until recently, no common pathophysiologic features were identified among cases diagnosed as Mikulicz syndrome, Riedel thyroiditis, Kuttner tumor, inflammatory pseudotumor, Ormond syndrome, and autoimmune pancreatitis. The discovery of IgG4 and the realization that some cases of sclerosing pancreatitis were associated with local accumulation of IgG4-positive plasma cells, extra-pancreatic involvement,2 and increased serum levels of IgG43 opened a new avenue of investigation that led to the recognition of IgG4-RD as a systemic disease that can involve virtually any organ. This and the fact that treatment with corticosteroids or with rituximab is often effective increased the importance of an accurate diagnosis of IgG4-RD. Confident identification of cases of IgG4-RD led to a better morphologic, immunohistochemical, and serologic characterization of this entity. Indeed, several morphologic features have been consistently described in cases of IgG4-RD: dense lymphoplasmacytic infiltrate, fibrosis with at least a focal storiform pattern, obliterative phlebitis, nonobliterative phlebitis, increased eosinophils, increased numbers of IgG4-positive plasma cells per high-power field (hpf), and increased IgG4/IgG plasma cell ratio (>40%). In addition, most patients have elevated serum IgG4 levels.4 After cases with varying presentations were analyzed, an interesting development was the realization that while features such as fibrosis, dense lymphoplasmacytic infiltrate, obliterative phlebitis, and elevated serum IgG4 are shared by most cases, there is significant variability in the morphologic manifestations of …
Many-to-many personalized communication with bounded traffic

This paper presents solutions for the problem of many-to-many personalized communication, with bounded incoming and outgoing traffic, on a distributed memory parallel machine. We present a two-stage algorithm that decomposes the many-to-many communication with possibly high variance in message size into two communications with low message size variance. The algorithm is deterministic and takes time 2t/spl mu/(+lower order terms) when t/spl ges/0(p/sup 2/+p/spl tau///spl mu/) Here t is the maximum outgoing or incoming traffic at any processor, /spl tau/ is the startup overhead and /spl mu/ is the inverse of the data transfer rate. Optimality is achieved when the traffic is large, a condition that is usually satisfied in practice on coarse-grained architectures. The algorithm was implemented on the Connection Machine CM-5. The implementation used the low latency communication primitives (active messages) available on the CM-5, but the algorithm as such is architecture-independent. An alternate single-stage algorithm using distributed random scheduling for the CM-5 was implemented and the performance of the two algorithms were compared. >
Identification of a Simple Chemical Structure Associated with Protective Human Antibodies against Multiple Pneumococcal Serogroups

Streptococcus pneumoniae, a major human pathogen, expresses at least 91 serologically distinct carbohydrate capsules. Since pneumococcal vaccines are designed to elicit antibodies against many different capsular polysaccharides (PSs), it is important to identify the epitopes involved in eliciting anti-capsular PS antibodies. We investigated the epitopes recognized by Dob1, which is a hybridoma-secreting human immunoglobulin G2 antibody to the PS of serotype 6B (Y. Sun et al., Infect. Immun. 67:1172-1179, 1999). We found that Dob1 bound synthetic capsular carbohydrates Gal(1-->3)alpha-d-Glcp(1-->3)alpha-l-Rhap(1-->3)Rib-ol and alpha-d-Glcp(1-->3)alpha-l-Rhap(1-->3)Rib-ol but did not bind alpha-l-Rhap(1-->3)Rib-ol. The critical epitope alpha-d-Glcp(1-->3)alpha-l-Rhap is found in the capsular PSs of serotypes 6A, 6B, 6C, and 19A but not in the 19F PS. Consistent with this observation, Dob1 bound to the PSs of serotypes 6A, 6B, 6C, and 19A but did not bind the 19F PS and 23 additional unrelated pneumococcal capsular PSs. Also, Dob1 could opsonize pneumococci expressing serotypes 6A, 6B, 6C, and 19A but did not opsonize 19F pneumococci. In addition, ca. 7% of immune sera (12 of 175 sera) had significant amounts of Dob1-like antibodies, i.e., reacted with 6B and 19A PSs, but not with 19F PS. Humans can produce antibodies to the Dob1 epitope and the antibodies to that epitope cross-react with the four serotypes 6A, 6B, 6C, and 19A that belong to different serogroups. This epitope may be useful for producing a totally synthetic, simple chemical structure that is capable of generating protective antibodies to multiple pneumococcal serogroups.
Measurement of Infrared Spectra of Dense Ceramics by Specular Reflectance Spectroscopy

It is shown that high-quality IR specular reflectance spectra can be obtained from polished surfaces of dense ceramics. The reflectance spectra can be deconvoluted by the Kramers-Kronig transformation to yield absorption spectra or the real and imaginary parts of the dielectric function. IR line shapes and peak wavenumbers are comparable to single-crystal data providing that the particle size is small compared with the IR wavelengths of interest. For noncubic structures, the spectra are a superposition of polarization components. Modes separated by less than a bandwidth are merged into a single band, thus limiting the resolution of the measurement procedure. Grain size effects were modeled using the spectra of single-crystal and polycrystalline quartz as an example.
Control Design and Performance Analysis of a 6 MW Wind Turbine-Generator

This paper discusses an approach to the modeling and performance for the preliminary design phase of a large (6.2 MW) horizontal axis wind turbine generator (WTG). Two control philosophies are presented, both of which are based on linearized models of the WT mechanical and electrical systems. The control designs are compared by showing the performance through detailed non-linear time simulation. The disturbances considered are wind gusts, and electrical faults near the WT terminals.
Scientific workflow scheduling in computational grids — Planning, reservation, and data/network-awareness

A very important issue in executing a scientific workflow in computational grids is how to map and schedule workflow tasks onto multiple distributed resources and handle task dependencies in a timely manner to deliver users' expected performance. In this paper, we present our work to develop and evaluate an advanced workflow scheduler in computational grid environments, the GRACCE scheduler. The GRACCE scheduler applies advanced scheduling techniques, such as resource negotiation and reservation, data/network-aware scheduling and performance prediction in the resource allocation and execution planning process. To evaluate the scheduler, we have set up an experimental environment that models a computational grid in those aspects relevant to workflow scheduling. Our results show the average performance improvement, using the GRACCE scheduler, is about 20% under high resource loads.