cssi/SciSciGPT-SciSciNet huggingface dataset:
NSAID inhibition of RGM1 gastric monolayer wound re-epithelialization: comparison of selective Cox-2 versus non-selective Cox inhibitors.

Clinical studies indicate that specific cyclooxygenase-2 (Cox-2) inhibitors are less ulcerogenic than their non-selective predecessors (e.g. indomethacin). However, Cox-2 inhibitors may also interfere with ulcer healing. Re-epithelialization is a crucial factor in both gastrointestinal mucosal injury and ulcer healing. This study was aimed to compare the effects of selective Cox-2 inhibitor (NS398) versus non-selective Cox inhibitor (indomethacin) on basal and basic fibroblast growth factor (bFGF) - stimulated gastric wound re-epithelialization. In-vitro epithelial wounds were created in confluent monolayers of RGM1 rat gastric epithelial cells by a razor blade scrape. Following wounding there was a significant re-epithelialization by 24 hrs. Indomethacin (0.25 mM and 0.5 mM) significantly inhibited basal wound re-epithelialization in a dose dependent manner. In contrast, selective Cox-2 inhibitor NS398 did not inhibit the basal re-epithelialization process. Basic FGF treatment produced significant enhancement of wound re-epitheliazation at the various concentrations [10, 20, 30, 40, 50 and 70 ng/ml] studied. Both indomethacin and NS398 inhibited bFGF stimulated wound re-epithelialization, with indomethacin having a greater inhibitory effect. The extent of NS398 inhibition was limited to the bFGF-stimulated component, whereas indomethacin inhibition extended to both the bFGF-stimulated and the basal re-epithelialization components. These findings indicate that specific Cox-2 inhibitor (NS398) does not interfere with the basal re-epithelialization but significantly inhibits the bFGF - stimulated re-epithelialization, whereas indomethacin interferes with both the basal as well as the bFGF-stimulated wound re-epithelialization.
Replacement of congenitally missing lateral incisors with ceramic resin-bonded fixed partial dentures

Congenital absence of teeth may accompany palatal clefts; various replacements are available and include conventional fixed partial dentures (FPDs), implant-supported artificial crowns, and resin-bonded FPDs. Orthodontic and restorative dentistry consultations are essential for appropriate treatment. The recent introduction of an all-ceramic resin-bonded FPD provides an esthetic prosthesis.
Epigenetic alterations in the breast: Implications for breast cancer detection, prognosis and treatment

Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. These modifications are quite appealing as targets for preventative care and therapeutics because of their potential for reversal. Future medical care for breast cancer patients will likely depend upon a better understanding of the roles epigenetic modifications play in carcinogenesis. Here, we discuss the importance of epigenetics in breast cancer detection, prognosis, and therapy with an emphasis on mechanisms and epigenetic contributions to field cancerization effects.
Assessing Crash Occurrence on Urban Freeways by Applying a System of Interrelated Equations

Most existing freeway crash frequency models analyze overall frequency of crashes. Furthermore, researchers have traditionally used average annual daily traffic (AADT) to represent traffic volume in their models. These two cases are examples of macroscopic crash frequency modeling. Segregating crashes on the basis of type of crash, peak or off-peak traffic conditions, lighting conditions, severity, and pavement condition could provide insight into the specific factors that affect each category. In this study multiple binary categorizations of the crashes were created to identify the factors associated with their frequencies and used geometric characteristics of the freeway and microscopic traffic variables that were based on loop detector data. These categorizations included multiple- and single-vehicle crashes, peak period and off peak period crashes, dry and wet pavement crashes, daytime and dark-hour crashes, and property-damage-only and injury crashes. Models for frequency of each of the two groups of crashes were estimated separately for all five categorizations. To account for correlation between the disturbance terms arising from omitted variables between any two models in a category, seemingly unrelated negative binomial (SUNB) regression was used for simultaneous estimation. SUNB estimation proved to be advantageous for multiple- and single-vehicle crashes and for daytime and dark-hour crashes. Road curvature and presence of on- or off-ramps were found to be the significant factors related to every crash category. Median type and pavement surface type were among other important factors affecting crashes. AADT was significant in most models and the 15-min coefficient of variation of speed was significant for frequency of daytime and peak period crashes. SUNB estimation proved to increase the efficiency of the crash frequency models by accounting for the disturbance correlation, reducing the standard errors, and providing better model fit.
Inverse seesaw in NMSSM and 126 GeV Higgs boson

Abstract We consider extensions of the next-to-minimal supersymmetric model (NMSSM) in which the observed neutrino masses are generated through a TeV scale inverse seesaw mechanism. The new particles associated with this mechanism can have sizable couplings to the Higgs field which can yield a large contribution to the mass of the lightest CP-even Higgs boson. With this new contribution, a 126 GeV Higgs is possible along with order of 200 GeV masses for the stop quarks for a broad range of tan β . The Higgs production and decay in the diphoton channel can be enhanced due to this new contribution. It is also possible to solve the little hierarchy problem in this model without invoking a maximal value for the NMSSM trilinear coupling and without severe restrictions on the value of tan β .
Energy metabolism in the whole animal revisited.

Abstract Dimensional analysis of animal with regard to those structures and functions which affects the rate of energy metabolism can be conducted on the basis of either geometric or eleastic similarity. Predictions of the trelationships between various structures and functions and body mass are dependent of the type of similarity assumed. Comparison of the relationships between numerous physiological variables and body mass resported in the literature and those predicted from geometric and elastic similarity indicates that the preponderance of predications from elastic similarity are in better agreement with the observed values than are the prediction from geometric similarity. It appears that the components of the cardiovascular system are scaled in accordance with elastic similarity. For this reason, cardiac output is proportional to body mass raised to the 3 4 power. The biochemical basis for the relationship between cardiac output and the rate of energy metabolism is discussed.
Modeling User Interactions in Social Communication Networks with Variable Social Vector Clocks

Social communication networks have been widely investigated in recent years. From fine-grained temporal information's point of view, social vector clock (SVC) is a useful mechanism to track the most recent communication with all other local peers in a social network. A modification of conventional social vector clocks has been proposed to deal with the issue of poor scalability without keeping whole temporal views [1]. In this paper, we propose an idea of variable social vector clocks (VSVCs) and the corresponding incremental algorithm. Not only does it maintain the lower bound of how out-of-date each peer can be with respect to others, but it also considers the shortest friendship separation to restrict how far information may be transmitted along time respecting paths. Unless this separation is bounded to be infinite, some communication messages could be lost implicitly. We also focus on studying message inconsistency and reachable in-degree communication distribution in several social networks based on variable social vector clocks.
Surface topography and electrical response of metal-electrolyte interfaces

Abstract The small-signal impedance of chemical cells with “blocking” electrodes is dominated at low frequencies ( f Hz ) by the impedance of the metal-electrolyte interfaces, which is accurately represented by Z rmi = A (j ω ) − n . The frequency exponent n , n n to the fractal dimension d of the rough interface. However, we have found no correlation between n and d from experiments using aqueous electrolytes and metal and semiconductor electrodes. A new model for the transient response of a rough electrode-electrolyte interface to a constant voltage pulse is proposed. Computer simulations, similar to the diffusion limited aggregation model, using measured profiles as fixed (non-growing) clusters, gave exponent n in good agreement with experiments.
Regulation of muscarinic receptor-mediated cyclic GMP synthesis by cultured mouse neuroblastoma cells

: Mouse neuroblastoma clone N1E-115 has muscarinic acetylcholine receptors that mediate cyclic GMP synthesis. This receptor-mediated response is not significantly higher than background until the cells have been maintained in the stationary phase for at least 1 week. The basis of the influence of time in culture on the cyclic GMP response was investigated. The relative amount of cyclic GMP synthesized by intact cells was measured by radioactively labeling the GTP pool with [3H]guanine, incubating cells with agonists, and then chromatographically isolating [3H]cyclic GMP. Carbamylcholine-, ionophore X-537A-, and sodium azide-induced cyclic GMP formation increased with time in culture to a maximum of 13-, 9-, and 2.5-fold above basal, respectively. There was no change in the number or the apparent affinity of the muscarinic receptors as measured by [3H]quinuclidinyl benzylate ([3H]QNB) binding. In addition, there was no change in the apparent affinity of the receptors for agonist as measured by the ability of carbamylcholine to displace the specific binding of [3H]QNB. Guanylate cyclase activity per milligram protein and per cell in-creased six- and sevenfold, respectively, from day 0 to day 22. However, this increase in guanylate cyclase appeared to precede the marked increase in sensitivity of the cells to agonists. These data suggest that, in addition to guanylate cyclase and muscarinic receptors, there is another factor which is responsible for the development of this muscarinic receptor-mediated response.
Aminothienopyridazines and Methylene Blue Affect Tau Fibrillization via Cysteine Oxidation

Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents.
Hexameric Macrocyclic Architectures in Heterocyclic Chemistry

Publisher Summary Transcending consideration of covalent versus non-covalent bonding, supramolecular chemistry considers building blocks instilled with angles, coordination sites, and affinities that drive their assembly to architectures with utilities and designs not accessed from the starting materials alone. This chapter discusses new developments in heterocyclic chemistry pertaining to hexameric macrocyclic architectures, highlighting salient synthetic features of ring construction whereby the participating heterocyclic building blocks, or subunits, possess at least one heteroatom, such as nitrogen, oxygen, or sulfur. The chapter also focuses on macrocycles with five-membered heterocyclic subunits, six-membered ring heterocycles, and some miscellaneous heterocyclic materials. The chapter emphasizes that the use of heterocyclic species, such as furan, pyrrole, thiophene, and pyridine, for the preparation of stable, hexameric (macro) molecular architectures has been demonstrated as a logical pathway to functional materials. This is based, in part, on the mature chemistry and ready availability of these versatile building blocks. Step-wise procedures and self-assembly protocols combined with ingenuity and creativity have led to the crafting of architecturally controlled species such as Stang's metal-directed metallocycles, Schlu¨ ter's bipyridine phenylacetylenes, Lehn's self-assembling helicates, and Newkome's bisterpyridine-based constructs.
Isotopic discrimination and kinetic parameters of RubisCO from the marine bloom‐forming diatom, Skeletonema costatum

The cosmopolitan, bloom-forming diatom, Skeletonema costatum, is a prominent primary producer in coastal oceans, fixing CO2 with ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) that is phylogenetically distinct from terrestrial plant RubisCO. RubisCOs are subdivided into groups based on sequence similarity of their large subunits (IA-ID, II, and III). ID is present in several major oceanic primary producers, including diatoms such as S. costatum, coccolithophores, and some dinoflagellates, and differs substantially in amino acid sequence from the well-studied IB enzymes present in most cyanobacteria and in green algae and plants. Despite this sequence divergence, and differences in isotopic discrimination apparent in other RubisCO enzymes, stable carbon isotope compositions of diatoms and other marine phytoplankton are generally interpreted assuming enzymatic isotopic discrimination similar to spinach RubisCO (IB). To interpret phytoplankton δ(13) C values, S. costatum RubisCO was characterized via sequence analysis, and measurement of its KCO2 and Vmax , and degree of isotopic discrimination. The sequence of this enzyme placed it among other diatom ID RubisCOs. Michaelis-Menten parameters were similar to other ID enzymes (KCO2 = 48.9 ± 2.8 μm; Vmax = 165.1 ± 6.3 nmol min(-1 ) mg(-1) ). However, isotopic discrimination (e = [(12) k/(13) k - 1] × 1000) was low (18.5‰; 17.0-19.9, 95% CI) when compared to IA and IB RubisCOs (22-29‰), though not as low as ID from coccolithophore, Emiliania huxleyi (11.1‰). Variability in e-values among RubisCOs from primary producers is likely reflected in δ(13) C values of oceanic biomass. Currently, δ(13) C variability is ascribed to physical or chemical factors (e.g. illumination, nutrient availability) and physiological responses to these factors (e.g. carbon-concentrating mechanisms). Estimating the importance of these factors from δ(13) C measurements requires an accurate e-value, and a mass-balance model using the e-value for S. costatum RubisCO is presented. Clearly, appropriate e-values must be included in interpreting δ(13) C values of environmental samples.
Gating of Shaker K+ channels: I. Ionic and gating currents

Ionic and gating currents from noninactivating Shaker B K+ channels were studied with the cut-open oocyte voltage clamp technique and compared with the macropatch clamp technique. The performance of the cut-open oocyte voltage clamp technique was evaluated from the electrical properties of the clamped upper domus membrane, K+ tail current measurements, and the time course of K+ currents after partial blockade. It was concluded that membrane currents less than 20 microA were spatially clamped with a time resolution of at least 50 microseconds. Subtracted, unsubtracted gating currents with the cut-open oocyte voltage clamp technique and gating currents recorded in cell attached macropatches had similar properties and time course, and the charge movement properties directly obtained from capacity measurements agreed with measurements of charge movement from subtracted records. An accurate estimate of the normalized open probability Po(V) was obtained from tail current measurements as a function of the prepulse V in high external K+. The Po(V) was zero at potentials more negative than -40 mV and increased sharply at this potential, then increased continuously until -20 mV, and finally slowly increased with voltages more positive than 0 mV. Deactivation tail currents decayed with two time constants and external potassium slowed down the faster component without affecting the slower component that is probably associated with the return between two of the closed states near the open state. In correlating gating currents and channel opening, Cole-Moore type experiments showed that charge moving in the negative region of voltage (-100 to -40 mV) is involved in the delay of the conductance activation but not in channel opening. The charge moving in the more positive voltage range (-40 to -10 mV) has a similar voltage dependence to the open probability of the channel, but it does not show the gradual increase with voltage seen in the Po(V).
A Plant-Specific Protein Essential for Blue-Light-Induced Chloroplast Movements

In Arabidopsis (Arabidopsis thaliana), light-dependent chloroplast movements are induced by blue light. When exposed to low fluence rates of light, chloroplasts accumulate in periclinal layers perpendicular to the direction of light, presumably to optimize light absorption by exposing more chloroplast area to the light. Under high light conditions, chloroplasts become positioned parallel to the incoming light in a response that can reduce exposure to light intensities that may damage the photosynthetic machinery. To identify components of the pathway downstream of the photoreceptors that mediate chloroplast movements (i.e. phototropins), we conducted a mutant screen that has led to the isolation of several Arabidopsis mutants displaying altered chloroplast movements. The plastid movement impaired1 (pmi1) mutant exhibits severely attenuated chloroplast movements under all tested fluence rates of light, suggesting that it is a necessary component for both the low- and high-light-dependant chloroplast movement responses. Analysis of pmi1 leaf cross sections revealed that regardless of the light condition, chloroplasts are more evenly distributed in leaf mesophyll cells than in the wild type. The pmi1-1 mutant was found to contain a single nonsense mutation within the open reading frame of At1g42550. This gene encodes a plant-specific protein of unknown function that appears to be conserved among angiosperms. Sequence analysis of the protein suggests that it may be involved in calcium-mediated signal transduction, possibly through protein-protein interactions.
Coordinatively and Electronically Unsaturated Tungsten(0) Carbonyl Complexes Stabilized by pi-Donating Amido Ligands.

Novel, coordinatively and electronically unsaturated tungsten tricarbonyl dianions of 2-aminophenol and 1,2-diaminobenzene have been synthesized from the reaction of photogenerated W(CO)(5)THF and [Et(4)N][OC(6)H(4)NH(2)] with subsequent deprotonation by [Et(4)N][OH] accompanied by facile CO dissociation, and the reaction of W(CO)(5)THF and 2 equiv of [Et(4)N][NHC(6)H(4)NH(2)], respectively. These air-sensitive derivatives have been fully characterized both in solution (nu(CO) and (13)C NMR) and in the solid-state (X-ray crystallography). These metal dianions which have formally 16e(-) configurations are stabilized by pi-donation from the amido groups of the chelating ligands, as evident from short W-N bond distances. Both solution (nu(CO) and (13)C NMR) and solid-state (W-N vs W-O bond distances) data on these derivatives indicate the amido ligand to be a better pi-donor than the oxo ligand. Complex 2 crystallized in the monoclinic space group P2(1)/n with a = 14.499(5) A, b = 14.708(5) A, c = 15.137(4) A, beta = 114.13(2) degrees, V = 2946(2) A(3), and d(calc) = 1.433 g/cm(3), for Z = 4. Complex 3 crystallized in the triclinic space group Po with a = 11.479(6) A, b = 11.786(8) A, c = 13.148(7) A, alpha = 102.41(5) degrees, beta = 91.27(4) degrees, gamma = 99.96(5) degrees, V = 1708(2) A(3), and d(calc) = 1.444 g/cm(3), for Z = 2.
TOPOLOGICAL-DEFECT SOLUTIONS IN LORENTZ-VIOLATING FIELD THEORIES

In other words, the Lagrangian for this theory in a dynamical spacetime consists of the usual Einstein-Hilbert action, a second-order kinetic term for the tensor field T , and a potential energy term for T . If we take the equations of motion associated with this metric, we can see that a field configuration where gab = ηab and T = T throughout spacetime will solve the equations of motion provided that
Shared attentional control of smooth eye movement and perception

Abstract Subjects performed a concurrent smooth pursuit and perceptual task to determine whether smooth pursuit eye movements and perception share the same attentional mechanism. Subjects pursued a pair of eccentric rows of moving characters while simultaneously attempting to identify and locate the single numeral in these target rows and the single numeral in a pair of untracked background rows, which moved at a different velocity. Average smooth pursuit gain (eye velocity/target velocity) was 0.7 to 1. Visual search was better for target rows (~ 65% correct) than for background rows (~ 22% correct). Superior search performance for the target was not due to its lower retinal speed: performance on the target was 2–3 times better than on the background when retinal speeds were the same. Superior performance for the pursuit target suggests that smooth eye movements and perception share the same selective attentional mechanism. A shared attentional mechanism was further supported by findings that subjects could not: (1) maintain a stable line of sight on a central stationary point while simultaneously attending to moving rows; and (2) pursue one pair of rows and attend the other, untracked rows. Attempts to attend untracked rows did, however, produce a partial improvement in search performance which was accompanied by only a very slight change in eye velocity. This demonstrates that the effects of decisions about how to apportion attention across the visual field depend on the task. Despite the common selective attentional mechanism, smooth eye movements do not provide accurate external indicators of attention unless the consequences of attentional decisions for performance are determined separately for oculomotor and for perceptual tasks.
Circular-arc cracks in bi-material plates under bending

Thin boundary problems of bimaterial plates bonded along circular arcs behaving like crack imperfections under bending, using fracture mechanics to predict failure
Coordinated intelligent adaptive control of legged robots

In planetary or hazardous environment exploration, there will be unforseen environmental circumstances which can not be planned. To overcome telerobotic control issues due to communication delays, autonomous robot control becomes necessary. Autonomously controlled landers and instrumentation can be used in exploration, such as lunar and martian missions. However, wheeled robots have difficulty in exploring uneven terrain; thus, legged robots can be used in such situations. This research develops intelligent and adaptive control of mobile robots to perform functions such as environmental exploration in coordination and obstacle avoidance. The coordinated control is demonstrated in simulations.
Gamma ray emission intensities of226Ra in equilibrium with its daughter products

A226 Ra source of known disintegration rate has been measured to determine the absolute γ-ray emission intensities of members of its decay chain in radioactive equilibrium. The results are compared with other values from the literature.
Group a streptococcal disease in the 1990s: New clues to pathogenesis

Abstract In the past decade, a resurgence of serious illness due to group A Streptococcus has occurred. After declining in incidence for more than 50 years, acute rheumatic fever reappeared in the United States in several locations in the mid-1980s. In the late 1980s, streptococcal toxic shock syndrome was recognized as an uncommon, but life-threatening form of infection manifested by shock and multiorgan failure. More recently, attention has focused on cases of streptococcal necrotizing fasciitis. The apparent global increase in the incidence of serious group A streptococcal disease syndromes has renewed interest in the epidemiology and pathogenesis of streptococcal infection and its sequelae. Recent studies implicate the dissemination of virulent strains, particularly the M1 and M3 serotypes, in the upswing of invasive disease. Pyrogenic exotoxins—the toxins responsible for scarlet fever—appear to play a pathogenic role in streptococcal toxic shock syndrome, perhaps through their T-ccell stimulatory activity as superantigens. Rheumatic fever has been associated with highly encapsulated strains of group A Streptococcus , and experimental studies have demonstrated that the hyaluronic acid capsule enhances the capacity of such strains both to colonize the pharynx and to cause invasive infection.
Protection against airsacculitis with sequential systemic and local immunization of chickens using killed Mycoplasma gallisepticum bacterin with iota carrageenan adjuvant

The induction of protective immunity to Mycoplasma gallisepticum (MG) by bacterins containing 0.2% iota carrageenan (iCGN) as an adjuvant has been studied. Various combinations of intracoelomic (i.c.), intratracheal (i.t.), intranasal (i.n.), intravenous (i.v.), subcutaneous (s.c.) and oral immunization routes were evaluated. Vaccinated and non-vaccinated groups were compared with a group vaccinated s.c. with a commercial bacterin. Primary i.c. immunization with the bacterin was as effective as commercial bacterin and was more effective when followed by i.n. or i.t. immunization. Oral immunization was ineffective, in contrast to observations reported with mice. The i.c./i.n. and i.c./i.t. combinations were the most effective, produced the highest levels of anti-MG IgG and IgA in serum and tracheobronchial washes, and sometimes provided 100% protection against air sac lesions. Chickens vaccinated by the i.c./i.n. or i.c./i.t. routes had the fewest virulent organisms in their respiratory tract secretions. These results demonstrated that i.c. immunization followed by local immunization with the bacterin is most efficacious in protecting chickens against airsacculitis.
A real-time scalable color quantizer trainer/encoder

In many color-imaging applications, it is desirable to display an image with as few different colors as possible with minimal loss in image quality. While good image quality is achievable using traditional vector quantization techniques, they are too slow for real-time video applications. An architectural design of a real-time, scalable color quantizer architecture is presented. It implements our fast tree structure vector quantization algorithm with a variable-size cubical prequantizer based on human perception proposed earlier. The design is scalable and uses different configurations of the processing and memory elements to process any 24-bit to 72-bit colors per input pixel to produce a 8-bit to 24-bit color palette. >
Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors

Oncogenic ROS1 fusion proteins are molecular drivers in multiple malignancies, including a subset of non-small cell lung cancer (NSCLC). The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor. Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors. Here, we profile the sensitivity and selectivity of seven ROS1 and/or ALK inhibitors at various levels of clinical development. In contrast to crizotinib's dual ROS1/ALK activity, cabozantinib (XL-184) and its structural analog foretinib (XL-880) demonstrate a striking selectivity for ROS1 over ALK. Molecular dynamics simulation studies reveal structural features that distinguish the ROS1 and ALK kinase domains and contribute to differences in binding site and kinase selectivity of the inhibitors tested. Cell-based resistance profiling studies demonstrate that the ROS1-selective inhibitors retain efficacy against the recently reported CD74-ROS1(G2032R) mutant whereas the dual ROS1/ALK inhibitors are ineffective. Taken together, inhibitor profiling and stringent characterization of the structure-function differences between the ROS1 and ALK kinase domains will facilitate future rational drug design for ROS1- and ALK-driven NSCLC and other malignancies.
Sea sick? Setting targets to assess ocean health and ecosystem services

The benefits provided by a healthy ocean are receiving increasing attention in policy and management spheres. A fundamental challenge with assessing ocean health and ecosystem services is that we lack a scientific framework for expressing ecosystem conditions quantitatively in relation to management goals. Here we outline and operationalize a conceptual framework for identifying meaningful reference points and quantifying the current ecosystem state relative to them. The framework requires clear articulation of management goals and is built on a review of current scientific understanding and assessment of data availability. It develops a structured approach for choosing among three classes of reference points, including: (1) functional relationships that establish the ocean state that can be produced and sustained under different environmental conditions, (2) time series approaches that compare current to previous capacities to obtain a particular ocean state in a specific location, and (3) spatial reference points that compare current capacities to achieve a desired ocean state across regional (or, if necessary, global) scales. We illustrate this general framework through the lens of ocean health defined in terms of a coupled social-ecological system, with examples from fisheries, marine livelihoods, and water quality in the USA. Assessment of ocean health and ecosystem services can be significantly influenced by the choice of indicators used to track changes in a management goal, the type of reference point selected, and how one measures the distance of the current state from the reference point. This framework provides flexible, standardized methods for evaluating ocean health and ecosystem services that can advance important components of ecosystem-based management, including marine spatial planning, ecosystem service valuation, and integrated ecosystem assessments.
Enhanced utilization bounds for QoS management

In many practical real-time applications, there is a given set of task frequencies (i.e., inverse of task periods) corresponding to predetermined QoS options that the applications can choose. For example, in audio applications, the typical choices of playback frequencies are for CD quality, radio quality, and phone quality. Similar configurations can be found in streaming video and in control applications. In such systems, applications dynamically arrive requesting one of the periods provided by the QoS manager. Thus, the accurate and efficient online schedulability test is essential for any task set whose periods are chosen from the QoS period set. For this purpose, we propose new utilization bounds as a function of given QoS periods. As long as there is a set of given periods that can be chosen by applications, the bounds developed can be used by the QoS manager to quickly determine the schedulability of dynamic applications.
A comparison of the new 2400 bps MELP Federal Standard with other standard coders

In 1996, the U.S. Department of Defense Digital Voice Processing Consortium (DDVPC) selected Texas Instrument's mixed excitation linear prediction (MELP) algorithm as the recommended new Federal Standard for 2400 bps voice communications. The algorithm selection process involved quality, intelligibility, communicability, and recognizability testing in many acoustic noise, error, and tandem conditions. Algorithm complexity was also measured. This paper compares the performance scores, diagnostic information, and complexity of MELP to the 4800 bps Federal Standard (FS1016) code excited linear prediction (CELP) algorithm, the 16 kbps continuously variable slope delta modulation (CVSD) algorithm, and the venerable Federal Standard (FIPS Pub. 137) 2400 bps linear predictive coding (LPC-10) algorithm.
Heat Kernel Analysis on Lie Groups

Spaces of maps from one finite dimensional manifold to another finite dimensional manifold provide a naturally occurring source of interesting infinite dimensional manifolds. The study of second order elliptic operators over some of these infinite dimensional manifolds has been the subject of much work in the past forty years, some of it for the purposes of quantum field theory and some of it for the purposes of stochastic analysis or infinite dimensional differential topology. In the latter category the domain manifold has usually been an interval or a circle. In these notes we will survey one particular topic in the analysis of a natural second order elliptic operatorLover such an infinite dimensional manifold.
On the characterization of stereoregular polymers. III. Polymethyl methacrylate

The tacticity theory previously reported was generalized so it could be applied to the proton magnetic resonance data obtained for a variety of methyl methacrylate polymers. This system is the only one known for which sufficient data exist or may be obtained to provide a test of the theory. From the data available, parameters characterizing the distribution of iso- and syndiotactic sequence lengths in each sample were obtained These parameters, in turn, were used to predict melting behavior for each sample capable of crystallization. The tacticity theory not only is consistent with the data on free radical-initiated (syndiotactic) polymers, about which there was no question of interpretation, it also provides an explanation for an uncertainty in the interpretation of the data on anionic-initiated (isotactic) polymers. Thus, in this case at least, the theory appears to provide a connection between experimentation and polymer configuration.
Long‐term effects of tetracyline on the subgingival microflora

Abstract. The long-term effect of tetracycline therapy on the subgingival microbiota was studied in a single patient, a 33-year-old female with advanced periodontal disease. Prior to antibiotic therapy, two initial plaque samples were collected to establish the baseline microbial data. These untreated samples contained high numbers of small and medium-sized spirochetes together with anaerobic Gram-negative rods including Bacteroides asac-charolyticus, Fusobacterium nucleatum, anaerobic “corroding” rods resembling the species B. corrodens but lacking a positive urease reaction, and a group of unidentified, non-fermenting anaerobic rods. The anaerobic asaccharolytic coccus, Peptostreptococcus micros, was also present as 7–10 % of the pretreatment flora. This complex, largely Gram-negative flora was changed to a facultative, saccharolytic plaque of streptococci (5. mitis and S. mutans) and actinomyces (A. viscosus and A. naeslundit) within 2 weeks of tetracycline therapy at 1000 mg per day. Rothia dentocariosa was the dominant organism cultured after an additional 2 weeks of 500 mg tetracycline per day. Of the predominant pretreatment flora, Fusobacterium nucleatum and Peptostreptococcus micros returned 6–8 weeks following therapy. The known pathogenic associations of this pair of organisms are discussed. However, there were no clinical manifestations of the recolonization by these organisms. Small spirochetes were observed, but not numerous, beginning 16 weeks after therapy. Two groups of organisms currently considered important in periodontal destruction, B. asaccharolyticus and the anaerobic “corroding” bacilli, did not return during the period of observation. High levels of tetracycline resistance were common among the Gram-positive cocci isolated during treatment.
How Web Site Organization Influences Free Recall, Factual Knowledge, and Knowledge Structure Density

Past research has demonstrated that nonlinear Web presentations (i.e., those that allow viewing in multiple orders) may lead to decreased free recall and learning of factual information compared to traditional, print-like linear Web designs. Recent evidence suggests, however, that nonlinear designs may facilitate learning of the interconnectedness of the presented information. This article presents experimental data from a combined sample of college students and adults (N = 172) manipulating site design and motivation designed to test for these various learning effects and to examine the potential influence of two mediating variables: selective scanning and elaboration. The central finding is that linear site designs encourage factual learning, whereas nonlinear designs increase knowledge structure density (KSD). The effects of elaboration and selective scanning, however, are mixed.
Learn to Communicate and Communicate to Learn

Thinking of a computer as an educational tool emphasizes a solitary interaction between the learner and the computer. A tool is something that is applied to an object in order to change it, and this usually implies a single user working on a single object or project. While tools are an important aspect of an educational experience, the tool metaphor can isolate individual learners from each other and from their teachers instead of cultivating a sense of educational community. Reconceptualizing the computer as a constructionist medium increases the computer's educational value, by allowing the development and support of communities of learners. As a medium, the computer is viewed as a collection of tools and capabilities that are used to communicate. This reconceptualization leads to a new class of computer applications that places constructionist activities within a more social context in which computers simultaneously provide opportunities for learning how to communicate as well as for enabling communication to enhance the learning experience. Computers are a particularly interesting educational medium, because not only do they allow communication via more traditional media (e.g. text, pictures and video), but they also enable the communication of ideas through the creation and sharing of computational objects (e.g. agents, simulations and analysis tools). As these computational objects become easier to create, share and combine, the educational opportunities afforded by the computer become more viable and effective. This article describes the AgentSheets system and its use as a constructionist medium in K-12 and university educational settings. Specifically, AgentSheets supports the social creation of SimCity-like interactive simulations by providing an environment for the definition and sharing of computational components, called agents, through the World Wide Web. Reviewers: Mary Beth Rosson (Virginia Tech.), Josie Taylor (Open U.) Interactive elements: The Agentsheets Behaviour Exchange is on the web, two simulations from which are embedded as Java applets. Video clips are also provided showing LEGOsheets applications in use. Interactive demonstrations:Agentsheets, Visual AgenTalk and the associated Behaviour Exchange are at http://www.cs.colorado.edu/~l3d/systems/agentsheets . The FishTank and Adding Machine simulations are embedded as Java applets (requiring a Java-aware Web browser ), and two video clips can be viewed of LEGOsheet applications in use (requiring a QuickTime player ).
Guanidinylated Neomycin Mediates Heparan Sulfate-dependent Transport of Active Enzymes to Lysosomes

Guanidinylated neomycin (GNeo) can transport bioactive, high molecular weight cargo into the interior of cells in a process that depends on cell surface heparan sulfate proteoglycans. In this report, we show that GNeo-modified quantum dots bind to cell surface heparan sulfate, undergo endocytosis and eventually reach the lysosomal compartment. An N-hydroxysuccinimide activated ester of GNeo (GNeo-NHS) was prepared and conjugated to two lysosomal enzymes, beta-D-glucuronidase (GUS) and alpha-L-iduronidase. Conjugation did not interfere with enzyme activity and enabled binding of the enzymes to heparin-Sepharose and heparan sulfate on primary human fibroblasts. Cells lacking the corresponding lysosomal enzyme took up sufficient amounts of the conjugated enzymes to restore normal turnover of glycosaminoglycans. The high capacity of proteoglycan-mediated uptake suggests that this method of delivery might be used for enzyme replacement or introduction of foreign enzymes into cells.
Self-dual embeddings of complete multipartite graphs

In this paper we examine self-dual embeddings of complete multipartite graphs, focusing primarily on Km(n) having m parts each of size n. If m = 2, then n must be even. If the embedding is on an orientable surface, then an Euler characteristic argument shows that no such embedding exists when n is odd and m 2, 3 (mod 4); there is no such restriction for embeddings on nonorientable surfaces. We show that these embeddings exist with a few small exceptions. As a corollary, every group has a Cayley graph with a self-dual embedding. Our main technique is an addition construction that combines self-dual embeddings of two subgraphs into a self-dual embedding of their union. We also apply this technique to nonregular multipartite graphs and to cubes.
Modularity and greed in double auctions

Designing double auctions is a complex problem, especially when there are restrictions on the sets of buyers and sellers that may trade with one another. The goal of this paper is to develop ``black-box reductions'' from double-auction design to the exhaustively-studied problem of designing single-sided mechanisms. We consider several desirable properties of a double auction: feasibility, dominant-strategy incentive-compability, the still stronger incentive constraints offered by a deferred-acceptance implementation, exact and approximate welfare maximization, and budget-balance. For each of these properties, we identify sufficient conditions on the two one-sided mechanisms --- one for the buyers, one for the sellers --- and on the method of composition, that guarantee the desired property of the double auction. Our framework also offers new insights into classic double-auction designs, such as the VCG and McAfee auctions with unit-demand buyers and unit-supply sellers.
NEW RING SYSTEMS OF ELEMENTS OF MAIN GROUPS IV AND V

Abstract The synthesis of [PhSn(O)O2CC6H11]6 represents the first example of tin(IV) in a drum-shaped molecule. The formation of the dimeric composition, [(MeSn(O)O2CC6H11)2(MeSn(O2CC6H11)3]2, appears to be an intermediate hydrolysis product on the way to the drum composition. The X-ray structure reveals an “unfolded” drum array. The distannoxane unit which is represented as the sides of the drum is found in additional new dimeric compositions, [(SCH2CH2O)2SnCl]2[H][Et4N], [((CN)2C2S2)2SnOH]2, and [BuSnCl2(OH) · H2O]2. These all have six-coordinated tin atoms which contrasts to the dimeric aryl distannoxanes recently isolated, [Ph2(Cl)SnOSnPh2(X)]2, X = OH, Cl, containing five-coordinated tin. Also isolated are the new ring containing, five-coordinated tin derivatives, [(SCH2CH2S)2Sn]2[SCH2CH2S][Et3NH]2 and [(SC(CN)C(CN)S)2SnMe][Et4N]. The former has two trigonal bipyramidal tin atoms while the latter composition has a square pyramidal geometry. Related ring systems of new five-coordinated derivatives of ...
On forecasting mortality

Official forecasts of mortality made by the U.S. Office of the Actuary throughout this century have consistently underestimated observed mortality declines. This is due, in part, to their reliance on the static extrapolation of past trends, an atheoretical statistical method that pays scant attention to the behavioral, medical, and social factors contributing to mortality change. A "multiple cause-delay model" more realistically portrays the effects on mortality of the presence of more favorable risk factors at the population level. Such revised assumptions produce large increases in forecasts of the size of the elderly population, and have a dramatic impact on related estimates of population morbidity, disability, and health care costs.
Trisomy 12 mosaicism confirmed in multiple organs from a liveborn child.

This patient, in whom trisomy 12 mosaicism was confirmed in multiple organs, is the fifth case diagnosed postnatally and the first reported for whom a meiotic origin of the trisomy, maternal meiosis I, was determined. Mosaic aneuploidy was suspected because of pigmentary dysplasia, a frequent but non-specific finding in chromosomal mosaicism. The severe phenotype of this child, who died in infancy with a complex heart malformation, was probably a result of the high percentage of trisomic cells. Cytogenetic and interphase fluorescent in situ hybridization analyses showed a highly variable distribution of aneuploid cells in the nine tissues studied, from none in blood and ovary to 100% in spleen and liver. The trisomy arose meiotically with apparent post-zygotic loss of one of the chromosomes 12; uniparental disomy for this chromosome in the diploid cell line was excluded. The phenotype of the cases reported in living or liveborn individuals has been extremely variable, ranging from the present case, in which the child died in infancy with multiple malformations and pigmentary dysplasia, to a fortuitous finding in an adult studied for infertility. The variation in severity is probably determined by the proportion and distribution of the trisomic cells, which is linked to the timing of the non-disjunctional error.
High-Accuracy X-Ray Diffraction Analysis of Phase Evolution Sequence During Devitrification of Cu50Zr50 Metallic Glass

Real-time high-energy X-ray diffraction (HEXRD) was used to investigate the crystallization kinetics and phase selection sequence for constant-heating-rate devitrification of fully amorphous Cu50Zr50, using heating rates from 10 K/min to 60 K/min (10 °C/min to 60 °C/min). In situ HEXRD patterns were obtained by the constant-rate heating of melt-spun ribbons under synchrotron radiation. High-accuracy phase identification and quantitative assessment of phase fraction evolution though the duration of the observed transformations were performed using a Rietveld refinement method. Results for 10 K/min (10 °C/min) heating show the apparent simultaneous formation of three phases, orthorhombic Cu10Zr7, tetragonal CuZr2 (C11b), and cubic CuZr (B2), at 706 K (433 °C), followed immediately by the dissolution of the CuZr (B2) phase upon continued heating to 789 K (516 °C). Continued heating results in reprecipitation of the CuZr (B2) phase at 1002 K (729 °C), with the material transforming completely to CuZr (B2) by 1045 K (772 °C). The Cu5Zr8 phase, previously reported to be a devitrification product in C50Zr50, was not observed in the present study.