cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulatory approved monoclonal antibodies contain framework mutations predicted from human antibody repertoires

Abstract Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using natural human antibody repertoire sequences. Our analysis shows that natural human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from natural human antibody sequence data. mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in natural human antibody repertoires. In addition, high frequency mutations in natural human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that natural human antibody repertoires may be useful as predictive tools to guide mAb development in the future.
Phosphorous-substituted redox-active ligands in base metal hydrosilylation catalysis

This article highlights the utilization of phosphine-containing redox-active ligands for efficient hydrosilylation catalysis. Manganese, iron, cobalt, and nickel precatalysts featuring these chelates have been described and leading activities for carbonyl, carboxylate, and ester C–O bond hydrosilylation have been achieved. Mechanistic studies have provided insight into the importance of phosphine hemilability.
The “I” of the Camera: To Have and Have Not Adapted a Film from a Novel

Ernest Hemingway and I were very good friends … I said to him, “I can make a picture out of your worst story.” He said, “What's my worst story?” I said, “Why, that goddamned piece of junk called To Have and Have Not …. – Howard Hawks This chapter describes some of the ways in which Howard Hawks's To Have and Have Not (Warner Brothers, 1944) cannot, and some of the ways it can, be regarded as an adaptation of the Hemingway novel. It analyzes some important respects in which the film differs in perspective and position from the novel, indeed constitutes a critique of it. And it concludes with some general observations about Hawks's films. Robin Wood asserts that Hawks cheated in his demonstration that he could make a film of Hemingway's worst story. “His movie is in no real sense a version of the novel. Only the first ten minutes – the scenes involving Mr. Johnson, the would-be big-game fisherman – have anything much to do with the original.” Although this assertion cannot ultimately be accepted, it is important to recognize its plausibility. For one thing, the Bogart–Bacall romance at the heart of Hawks's To Have and Have Not departs drastically from the relationship of Harry Morgan and Marie Browning as Hemingway presents it. Physically, Hemingway's hefty, middle-aged ex-prostitute is poles apart from the young world-traveler Bogart insists on calling “Slim” (as she insists on calling him “Steve,” although his name is Harry).
A different construction of Gaussian fields from Markov chains: Dirichlet covariances

Abstract We study a class of Gaussian random fields with negative correlations. These fields are easy to simulate. They are defined in a natural way from a Markov chain that has the index space of the Gaussian field as its state space. In parallel with Dynkin's investigation of Gaussian fields having covariance given by the Green's function of a Markov process, we develop connections between the occupation times of the Markov chain and the prediction properties of the Gaussian field. Our interest in such fields was initiated by their appearance in random matrix theory.
Gary Tomlinson, The Singing of the New World: Indigenous Voice in the Era of European Contact

The title of Gary Tomlinson's The Singing of the New World is intentionally ambiguous, referring both to an activity of enormous importance to indigenous cultures in the Americas at the time of the...
Serum concentration of bile acids in relation to the normal menstrual cycle, the administration of oral contraceptives, and pregnancy

The effects of endogenous and exogenous steroids on serum levels of bile acid glycine conjugates were investigated by measuring these serum levels in 10 healthy women during normal menstrual cycle in 10 healthy women during a cycle of combination oral contraceptives (OCs) (50-100 mcg of ethinyl estradiol or mestranol) and in 27 healthy women during normal pregnancy. Peripheral venous blood was obtained from nonpregnant patients on Days 2 6 12 18 and 24 after onset of uterine bleeding. No significant differences in glycocholic and glycochenodeoxycholic acid serum levels occurred at any point in the cycle. Similarly no significant differences were noted between patients receiving OCs and those with normal menstrual cycles. Fasting peripheral blood samples from the 27 pregnant volunteers (collected throughout the 3 trimesters) also revealed no significant serum level differences during any trimester. Physiologic changes in endogenous estrogens and progesterones have no appreciable effect on the bile acid serum levels measured; nor apparently do moderate doses of synthetic estrogens in OCs alter bile acid serum levels in healthy women.
Growth and Inhibition of Microorganisms in the Presence of Sorbic Acid: A Review

Sorbate (sorbic acid) generally is an effective inhibitor of most molds and yeasts and some bacteria. Environmental factors such as pH, water activity, temperature, atmosphere, microbial load, microbial flora and certain food components can influence the effectiveness of sorbate. Strains of microorganisms resistant to sorbate exist and therefore are common causes of food spoilage. Some molds and bacteria are able to degrade sorbate. This paper reviews the factors that affect the antimicrobial effectiveness of sorbate in foods.
Galactic HII Regions, Anomalous 1720 MHz OH Clouds and Spiral Structure in the Galaxy

We have compared velocity-longitude diagrams of bright, galactic HII regions and 1720 MHz OH clouds against diagrams predicted by the ballistic particle model. Independent of our model, both velocity longitude diagrams suggest the presence of spiral arms. In addition, our ballistic particle model produces velocity-longitude diagrams which resemble both observed ones. Our model assumes a two-arm spiral pattern and that the objects in question are seen less than 50 million years after their launching, at the post-shock velocity, from the TASS wave.
Endoscopic transsphenoidal surgery.

Background: Endoscopic transsphenoidal surgery was developed under a minimally invasive surgical strategy. This endonasal transsphenoidal endoscopy eliminates a sublabial or transfixional incision, the use of a transsphenoidal retractor and any nasal packing.
Practical Reinforcement Learning in Continuous Spaces

Dynamic control tasks are good candidates for the application of reinforcement learning techniques. However, many of these tasks inherently have continuous state or action variables. This can cause problems for traditional reinforcement learning algorithms which assume discrete states and actions. In this paper, we introduce an algorithm that safely approximates the value function for continuous state control tasks, and that learns quickly from a small amount of data. We give experimental results using this algorithm to learn policies for both a simulated task and also for a real robot, operating in an unaltered environment. The algorithm works well in a traditional learning setting, and demonstrates extremely good learning when bootstrapped with a small amount of human-provided data.
Changing Fortunes: Biodiversity and Peasant Livelihood in the Peruvian Andes

Changing Fortunes: Biodiversity and Peasant Livelihood in the Peruvian Andes. Karl S. Zimmerer. Berkeley: University of California Press, 1996. 308 pp.
Effect of Perfusion Rate on Absorption, Surface Area, Unstirred Water Layer Thickness, Permeability, and Intraluminal Pressure in the Rat Ileum in Vivo

Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.
Bis[4‐(tridecafluorohexyl)phenyl] Diselenide

[234449-42-4] C24H8F26Se2 (MW 948.20) InChI = 1S/C24H8F26Se2/c25-13(26,15(29,30)17(33,34)19(37,38)21(41,42)23(45,46)47)9-1-5-11(6-2-9)51-52-12-7-3-10(4-8-12)14(27,28)16(31,32)18(35,36)20(39,40)22(43,44)24(48,49)50/h1-8H InChIKey = YCRFNIGNXWPRSG-UHFFFAOYSA-N (reagent used as a recyclable fluorous1, 2 alternative to diphenyl diselenide) Physical Data: mp 95–97 °C, yellow crystalline solid.3 Solubility: soluble in CH2Cl2, CHCl3, THF, and FC-72. Analysis of Reagent Purity: 1H, 13C, 19F, and 77Se NMR; elemental analysis.3 Preparative Methods: the title reagent is prepared from 4-perfluorohexylphenyl selenocyanate by borohydride reduction followed by exposure to air (eq 1).3 The fluorous selenocyanate is obtained from the corresponding diazonium salt by treatment with potassium selenocyanate. The synthesis of the diazonium salt involves copper-mediated coupling of 4-iodoaniline with perfluorohexyl iodide, and subsequent reaction with isoamyl nitrite (eq 1).3 (1) Purification: recrystallized from EtOH. Handling, Storage, and Precautions: stable reagent, stored under argon, may be toxic.
Studies of Peripheral Blood T- and B-Lymphocytes in Acute Infections

E-binding (T) and immunoglobulin-bearing (B) lymphocytes were determined in 22 patients with acute infections. The percentage of T-cells was depressed in most patients in the early stages of disease, whereas the B-cell proportion was usually elevated compared with convalescence and controls. The B-cell increase occurred earlier in a small group of viral or mycoplasmal infections than in bacterial infections. Four patients with unusually high numbers of B-cells had no corresponding increase in EAC3-binding lymphocytes. Almost all lymphocytes from pleural effusion in a patient with tuberculosis were found to be T-cells.
Information Technology Standards Choices and Industry Structure Outcomes: The Case of the U.S. Home Mortgage Industry

Vertical IS standards prescribe data structures and definitions, document formats, and business processes for particular industries, in contrast to generic information technology (IT) standards, which concern IT characteristics applicable to many industries. This paper explores the potential industry structure effects of vertical information systems (IS) standards through a case study of the U.S. home mortgage industry. We review theoretical arguments about the potential industry structure effects of standards for interorganizational coordination, and we compare the characteristics of XML-based vertical IS standards with those of electronic data interchange (EDI) to gauge the applicability of prior literature. We argue that the lower costs and wider accessibility of XML-based standards that use the Internet can result in significant changes to the structure of the mortgage industry. However, the nature of industry change will depend on the specific ways in which standards are implemented by organizations in the industry--there are many patterns of implementation with potentially different effects at the industry level of analysis. We illustrate these theoretical arguments with data from our case.
Nonlinear output tracking via nonlinear dynamic sliding manifolds

A multi-input-multi-output (MIMO) nonlinear output tracking problem with unmatched nonlinearities and disturbances is considered. The solution of this problem is addressed by methods of variable structure control. The nonlinear transformation of the coordinates of the initial nonlinear system, based on "remaining dynamics" is found. This transformation changes the system to a form convenient for the sliding mode synthesis. The sliding surface as a nonlinear dynamic operator has been designed to provide the desired linear performance of the output tracking error in the sliding mode. The system with such a sliding mode controller has obtained the combined features of the system with the conventional compensator (accommodation to the unmatched disturbances) and the conventional sliding mode controller (insensitivity to the matched disturbances). >
Measuring the viscoelastic properties of human platelets with the atomic force microscope

We have measured force curves as a function of the lateral position on top of human platelets with the atomic force microscope. These force curves show the indentation of the cell as the tip loads the sample. By analyzing these force curves we were able to determine the elastic modulus of the platelet with a lateral resolution of approximately 100 nm. The elastic moduli were in a range of 1–50 kPa measured in the frequency range of 1–50 Hz. Loading forces could be controlled with a resolution of 80 pN and indentations of the platelet could be determined with a resolution of 20 nm.
Thermal focusing effects on the supercontinuum.

Etude de la phase de l'impulsion, de la forme spectrale du supercontinuum et du diametre du faisceau en presence des gradients de temperature
Heavy-section steel technology program overview

Abstract This paper presents a status review of ongoing HSST program tasks aimed at refining the technology used in analysis of reactor pressure vessel fracture margins under pressurized thermal-shock (PTS) loading. Specific fracture-technology issues addressed include vessel flaw density and distribution, shallow flaws, fractures-toughness data transfer, circumferential cracks, ductile tearing and the influence of low-tearing toughness in stainless steel cladding. Preliminary results from the analysis and test programs are presented, together with interim assessments of their potential impact on a reactor vessel PTS analysis.
Color doppler echocardiography.

Color Doppler flow mapping is a useful new imaging modality which provides near real-time information about the direction and character of intracardiac flows. Color Doppler is especially useful in the diagnosis and quantitation of valvular regurgitation, and in the detection of intracardiac shunts. Color Doppler is a useful adjunct to CW Doppler in the assessment of valvular stenosis, as a means of aligning the ultrasound beam parallel to the direction of the stenotic jet. Limitations of color flow imaging with regards to absolute velocity and the timing of intracardiac flows can be overcome by using pulse, CW, or color M-mode in conjunction with the two-dimensional color flow examination.
A data analysis of residential demand for natural gas using step‐down multiple comparison tests

Multiple comparison tests are not ordinarily employed in econometric analysis. An example of the application of a step-down approach to a much studied problem is set forth. Comments on the estimated results and on the relevance of these tests to the present and other economic analyses are also presented. The application of the multiple comparison tests aids in the identification of a relatively simple regression equation of residential natural gas demand.
A vortex wake capturing method for potential flow calculations

A method is presented for modifying finite difference solutions of the potential equation to include the calculation of non-planar vortex wake features. The approach is an adaptation of Baker's 'cloud in cell' algorithm developed for the stream function-vorticity equations. The vortex wake is tracked in a Lagrangian frame of reference as a group of discrete vortex filaments. These are distributed to the Eulerian mesh system on which the velocity is calculated by a finite difference solution of the potential equation. An artificial viscosity introduced by the finite difference equations removes the singular nature of the vortex filaments. Computed examples are given for the two-dimensional time dependent roll-up of vortex wakes generated by wings with different spanwise loading distributions.
Embarrassment and Helping Behavior

Two experiments were devised to test Goffman's contention that embarrassment provokes face-restoring behavior on the part of spectators to the embarrassment as long as the embarrassed person does not violate the norms of interaction and does not regain composure. When a confederate requests students to volunteer for a study: students will be more likely to volunteer as subjects when the requester loses composure than when the requester docs not lose composure and students will be less likely to volunteer when the requester loses composure and fails to regain it than when he performs without losing composure. Results confirmed both hypotheses.
Indoleacetic acid oxidase

S p e c ifi c ialty nctio f.-th e E n z y m e .__ '''.'''.'.........-.''.--''''''''''''''''-'-' -'-''''113 Specifici y of the Enzyme 134 Chemistry of the Enzyme ..... 135 Mechanism of Action 13 5 Oxidation Products.13 8 Factors Influencing Action.141 Temperature, Oxygen, Time, Concentrations .141 1H.141 Natural Inhibitors.141 Occurrence and Distribution.143 Chemistry.143 Physiological Function.144 Lght.144 Daylength.146 Chemical Promoters.147 Coenzymes ... 147 Inhibitor Removers and Inactivators.150 Chemical Inhibitors 151 Direct Enzyme Inhibitors . .. .151 Com petitive Inhibitors 1.........5.. 141 Coenzyme Oxidation ......... 153 Natural Inhibitor Promotion. 153 Non-enzymatic Destruction of IAA 156 Assay Techniques 157 Extraction and Puriication 157 Incubation .Rv . ..... 157 Determination ......... 158 Literature Citedn.158.xiato 158
The three-parameter corresponding states principle

A multiproperty approach for the evaluation of the existing three-parameter corresponding states principles (CSP) and calculation of the corresponding states parameter is presented. This technique is based on the assumption that contribution of the third parameter to the thermophysical properties is much smaller than the contributions of the first two parameters. The first two parameters are, generally, the molecular energy and length parameters, e/k and σ (or critical temperature and volume, T c and V c ). Based on the present multiproperty technique, several existing three-parameter CSPs are evaluated. It is demonstrated that the three-parameter CSP, which is based on the two- and three-body intermolecular potential parameters, effectively satisfies the requirements of this technique. The corresponding states parameters of several compounds, including normal alkane hydrocarbons (CH4 to C20H42), for which proper thermophysical data are available, are calculated through the present technique, and they are reported here.
An experimental study of the double slip deformation hypothesis for face-centred cubic single crystals

Abstract Direct x-ray measurements during deformation are compared with single slip and double slip calculations for rotations beyond the symmetry line. Both a literature survey of 152 face-centred cubic tests since 1923 and the present studv of 16 aluminium tests reveal that the use of the automatic double slip calculation for resolved data is not a reliable procedure. No test since 1929, including the present series, for which rotations have been measured during deformation have turned at the symmetry line in the manner predicted for the double slip hypothesis.
The Early History of Wheat Improvement in the Great Plains

More than 60% of U.S. wheat is grown in the Great Plains. Three classes of common wheat (Triticum aestivum L.)—hard red spring, hard red winter, and hard white—and durum (T. turgidum L. var. durum) occupy 16 million ha in the region and provide most of the U.S. grain for baked goods and pasta. This article relates the early history of the four classes and the key persons involved in their establishment. Pioneers faced many difficulties in settling the Plains, but the need for adapted cultivars was paramount. Three cultivars—‘Red Fife’ hard red spring wheat, ‘Turkey’-type hard red winter wheat, and ‘Kubanka’ durum wheat—were the foundation for the industry. Red Fife was selected by D.A. Fife of Ontario in 1842. The cultivar spread to the northern U.S. Plains during the 1860s and dominated production for 40 yr. Turkey hard red winter wheat was introduced to Kansas by Mennonite settlers from the Ukraine, particularly B. Warkentin, in 1873 and was advanced by C.C. Georgeson, who recognized its potential. Another cultivar, ‘Kharkof’, introduced by M.A. Carleton in 1900, stimulated spread of the class throughout the Plains. Carleton also introduced Kubanka in 1900 and promoted its utilization to start the U.S. durum industry. The most recent class, hard white wheat, was initiated by E.G. Heyne and approved by the USDA in 1990. These wheats transformed American agriculture by opening a vast area for production, shifting the center of cultivation to the Plains, and changing the country into a major grain exporter.
Attenuation of NMDA Receptor Activity and Neurotoxicity by Nitroxyl Anion, NO−

Recent evidence indicates that the NO-related species, nitroxyl anion (NO), is produced in physiological systems by several redox metal-containing proteins, including hemoglobin, nitric oxide synthase (NOS), superoxide dismutase, and S-nitrosothiols (SNOs), which have recently been identified in brain. However, the chemical biology of NO- remains largely unknown. Here, we show that NO- -unlike NO*, but reminiscent of NO+ transfer (or S-nitrosylation)- -reacts mainly with Cys-399 in the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor to curtail excessive Ca2+ influx and thus provide neuroprotection from excitotoxic insults. This effect of NO- closely resembles that of NOS, which also downregulates NMDA receptor activity under similar conditions in culture.
Atomic transitions in ultrastrong laser fields

We have calculated the ionization rate of hydrogen by an intense electromagnetic field in the dipole approximation and in an approximation in which this field dominates the electron-proton interaction in intermediate states. We find the transition rate behaves as ${E}^{\ensuremath{-}1}$ for linearly polarized fields and ${E}^{\ensuremath{-}2}\mathrm{ln}E$ for circularly polarized fields where $E$ is the amplitude of the electric field. We have also calculated the transition rate for excitation of the $2s$ state and a Raman photon. The result behaves as (${E}^{\ensuremath{-}2}W$) for small $W$ where $W$ is the energy of the Raman photon. We estimate that the method is a good one for electric field strengths of the order of 2\ifmmode\times\else\texttimes\fi{}${10}^{11}$ V/cm or higher. This is larger than available currently.
MODELS OF DISTRIBUTED-SHARED-MEMORY ON AN INTERCONNECTION NETWORK FOR BROADCAST COMMUNICATION

Due to advances in fiber-optics and VLSI technology, interconnection networks which allow multiple simultaneous broadcasts are becoming feasible. This paper examines the performance of distributed-shared-memory (DSM) systems based on the Simultaneous Optical Multiprocessor Exchange Bus (SOME-Bus) using queuing network models and develops theoretical results which predict processor utilization, message latency and other useful measures. It also presents simulation results which compare the performance of the SOME-Bus, the mesh and the torus using queuing-network models. The SOME-Bus is a low-latency, high-bandwidth, fiber-optic interconnection network which directly links arbitrary pairs of processor nodes without contention, and can efficiently interconnect over one hundred nodes. It contains a dedicated channel for the data output of each node, eliminating the need for global arbitration and providing bandwidth that scales directly with the number of nodes in the system. Each of the N nodes has an array of receivers, with one receiver dedicated to each node output channel. No node is ever blocked from transmitting by another transmitter or due to contention for shared switching logic. The entire N-receiver array can be integrated on a single chip at a comparatively minor cost resulting in o(N) complexity. The SOME-Bus has much more functionality than a crossbar by supporting multiple simultaneous broadcasts of messages, allowing cache consistency protocols to complete much faster. The effect of collective communications due to cache coherence is examined. Results reveal that the performance of the SOME-Bus interconnection network is the least affected by large communication times, compared to the other two architectures considered here. Even in the presence of intense coherence traffic, processor utilization and message latency is much less affected than in the other architectures.
A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal

The pathogenic bacterium Pseudomonas aeruginosa uses acyl-homoserine lactone quorum-sensing signals to coordinate the expression of a battery of virulence genes in a cascade of regulatory events. The quorum-sensing signal that triggers the cascade is N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), which interacts with two signal receptor-transcription factors, LasR and QscR. This signal is base labile, and it is degraded by mammalian PON lactonases. We have identified a structurally unrelated triphenyl mimic of 3OC12-HSL that is base-insensitive and PON-resistant. The triphenyl mimic seems to interact specifically with LasR but not with QscR. In silico analysis suggests that the mimic fits into the 3OC12-HSL-binding site of LasR and makes key contacts with LasR. The triphenyl mimic is an excellent scaffold for developing quorum-sensing inhibitors, and its stability and potency make it ideal for biotechnology uses such as heterologous gene expression.
Induction of methotrexate release from rat hepatocytes in suspension by α-adrenergic agents: Involvement of calcium and metabolic energy

Abstract Hepatocytes in suspension which have accumulated [ 3 H]methotrexate release the antifolate compound into the medium upon exposure to α-adrenergic agents. In the presence of metabolic poisons, such as sodium azide, dinitrophenol, or dicumarol, the release of methotrexate is attenuated, indicating that integrity of the cellular metabolic apparatus is required for response to the hormonal stimulus. In the presence of millimolar concentrations of the organic acid, probenecid, release of cellular methotrexate may be reduced (1 m m probenecid) or eliminated (2 m m probenecid), suggesting the involvement of a “membrane carrier.” Microtubule poisons such as vincristine, vinblastine, and griseofulvin do not modify epinephrine + isobutyl methyl xanthine (IBMX)-induced release of methotrexate. The involvement of calcium in release of methotrexate from the hepatocyte is substantiated by a dose-dependent response to the calcium ionophore, A23187, in the presence of calcium, with a lack of response in the absence of calcium. These effects of A23187 are not related to inhibition of methotrexate influx. Other putative “calcium antagonists” such as tetracaine, neomycin sulfate, and 3,4,5-trimethoxybenzoic acid [8-(diethylamino)octyl ester], do not interfere with epinephrine + IBMX-induced release of [ 3 H]methotrexate, suggesting that these agents may not be effective probes of calcium flux in the liver cell.
Next Steps--Looking to the Future.

This chapter describes the influence of emerging challenges on the AACC competencies that successful leaders must draw upon the most and why new competencies may be needed in the future.
Video registration to geo-referenced imagery

The problem of accurately registering an aerial video image to geo-referenced imagery has become more important in recent years. To achieve high efficiency, we propose a guided hierarchical searching scheme to augment the current geo-registration framework. The algorithm consists of three major steps. In the first step, the reference image and video frames are projected to a common coordinate system based on the telemetry. In the second step, feature points are extracted in the video and reference, and the coarse searching for the best match was performed on a feature points image pyramid, where the comparison process is only applied to the regions with feature points. In the final step, the precise transformation parameters are estimated using the Levenberg-Marquardt techniques, which results in a precise alignment of the video and reference. Compared with conventional blind comparison based on the normalized cross-correlation measure, the proposed approach differes because it applies a feature-based hierarchical searching scheme to quickly lead the matching process to the most likely protion in the reference and speed up the matching process. Experimental results that evaluate the developed approach using real world aerial video will be presented. The obtained results demonstrate that our proposed method can be used in a complete geo-registration system to provide accurate registration of the video frames.
Right hemispheric dominance for mediating cerebral activation.

Abstract Patients with right-hemisphere lesions have been shown to have slower simple reaction times than patients with left-hemisphere lesions. To determine whether the right hemisphere dominates activation (physiologic readiness to response), we gave 24 normal subjects lateralized warning stimuli followed by central reaction time stimuli. Warning stimuli projected to the right hemisphere reduced reaction times of the right hand more than warning stimuli projected to the left hemisphere reduced left hand reaction times. Warning stimuli projected to the right hemisphere reduced reaction times of the right hand even more than warning stimuli projected directly to the left hemisphere. These results support the hypothesis that the right hemisphere dominates activation.
An external gas supply system for a Van De Graaff positive ion accelerator

Abstract A simple system, which allows an ion source gas bottle (located in the terminal of the accelerator) to be pressurized through copper and polypropylene tubing from an external gas cylinder, is described. Since it is not necessary to remove the insulating gas from the accelerator tank, a complete change in accelerated ions can be made in 30 min or less. Electrical breakdowns in the polypropylene tubing (with subsequent rupture) is prevented by backfilling with insulating gas.
Evolutionary and molecular analyses of the Borrelia bdr super gene family: delineation of distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs.

Abstract B. turicatae , a causative agent of relapsing fever, carries a polymorphic gene family that is homologous to the bdr gene family of the Lyme disease spirochetes (previously referred to as the rep + or ORF-E gene family). Here we demonstrate that bdr related genes are widely distributed among pathogenic Borrelia species and exist as large, polymorphic, plasmid carried, gene families. Twenty distinct bdr alleles were identified in isolates of the relapsing fever spirochete, B. hermsii , and were localized to linear plasmids. Cloning and sequence analyses demonstrate that the putative Bdr functional domains (i.e. the phosphorylation motifs and the transmembrane C-terminal domain) are conserved across the genus while other regions of these proteins exhibit variability. An assessment of the evolutionary relationships among all known Bdr protein sequences obtained from five pathogenic Borrelia species revealed that there are distinct Bdr sub-families. The recognition of distinct phyletic clusters serves as the basis of a revised and simplified nomenclature for the bdr proteins that can be applied genus wide. At the biological level the delineation of multiple bdr sub-families within isogeneic populations raises the possibility that there may be functional partitioning among alleles. In summary, the distribution and conservation of the Bdr proteins suggests that they are important in the biology/pathogenesis of the Borrelia at the genus wide level.
Calibration of a 137Cs γ-ray beam irradiator using large size chambers

Abstract A 137 Cs γ -ray beam irradiator has been calibrated in terms of air kerma using large size chambers. The available air-kerma rates range between 1.8 μGy/h (0.2 mR/h) and 5.3 mGy/h (0.6 R/h). Large-volume chambers were used to characterize the source in terms of the radiation quantity air kerma (and exposure). Two types of chambers with significantly different characteristics and energy responses were used. This work shows that very good agreement can be obtained between the measurements performed with such different types of chambers. An agreement of 0.3% is observed between chambers even for the lowest air-kerma rates measured.
Modeling low cost hybrid tandem photovoltaics with the potential for efficiencies exceeding 20

It is estimated that for photovoltaics to reach grid parity around the planet, they must be made with costs under $0.50 per Wp and must also achieve power conversion efficiencies above 20% in order to keep installation costs down. In this work we explore a novel solar cell architecture, a hybrid tandem photovoltaic (HTPV), and show that it is capable of meeting these targets. HTPV is composed of an inexpensive and low temperature processed solar cell, such as an organic or dye-sensitized solar cell, that can be printed on top of one of a variety of more traditional inorganic solar cells. Our modeling shows that an organic solar cell may be added on top of a commercial CIGS cell to improve its efficiency from 15.1% to 21.4%, thereby reducing the cost of the modules by ∼15% to 20% and the cost of installation by up to 30%. This suggests that HTPV is a promising option for producing solar power that matches the cost of existing grid energy.
Adjustment of Stream Channel Capacity Following DAM Closure, Yegua Creek, Texas

: In Yegua Creek, a principal tributary of the Brazos River in Texas, surveys of a 19 km channel reach downstream of Somerville Dam show that channel capacity decreased by an average of 65 percent in a 34 year period following dam closure. The decrease corresponds with an approximately 85 percent reduction in annual flood peaks. Channel depth has changed the most, decreasing by an average of 61 percent. Channel width remained stable with an average decrease of only 9 percent, reflecting cohesive bank materials along with the growth of riparian vegetation resulting from increased low flows during dry summer months. Although large changes in stream channel geometry are not uncommon downstream of dams, such pronounced reductions in channel capacity could have long-term implications for sediment delivery through the system.
Developmental changes in the relationship between IGF-I and body composition during puberty

To examine the hypothesis that anthropometric measures and physical fitness influence circulating insulin-like growth factor-I (IGF-I) during puberty, we measured IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 concentrations in 156 healthy girls (9-16 years old) characterized by aerobic capacity (VO2max), fat-free mass (FFM), percent fat mass and pubertal development. IGF-I, free IGF-I and IGFBP-3 increased with pubertal development while IGFBP-1 declined. Percent fat mass correlated inversely with IGFBP-1 (r = -0.57) and directly with insulin (r = 0.50), while VO2max correlated inversely with percent fat mass (r = -0.63), body mass index (BMI, r = -0.57), and FFM (r = -0.40). When subdivided by Tanner stage, IGF-I correlated directly with weight, height, BMI, and FFM in pre-pubertal girls, but these relationships all diminished or disappeared completely by late puberty. Inverse correlations between IGF-I and percent fat mass, and direct correlations between IGF-I and VO2max as observed previously in adults, were not seen until late puberty. These data suggest that in pre-pubertal and early pubertal girls, IGF-I concentrations in blood reflect overall somatic size. This relationship between IGF-I and body size diminishes with sexual maturation, while correlations between IGF-I and both fitness and fatness emerge.
Assembly of Clathrin Coats Disrupts the Association between Eps15 and AP-2 Adaptors

Eps15 is a phosphorylation substrate of the epidermal growth factor receptor kinase. In vivo, it is largely found in complex with AP-2, the plasma membrane clathrin adaptor protein complex. Although AP-2 is uniformly distributed across the surface of clathrin-coated pits and vesicles, Eps15 is preferentially found in the rims of endocytic clathrin-coated pits (1). This observation suggests that Eps15 may disengage from AP-2 during coat formation. Here we use two new anti-Eps15 antibodies to show that, contrary to our own earlier suggestion, coated vesicles isolated from brain do not contain detectable amounts of Eps15. Furthermore, when AP-2 complexes that are saturated with Eps15 are used for in vitro assembly of clathrin-AP-2 coats, normal structures are formed that contain the expected amounts of clathrin and AP-2, but the amount of Eps15 present is dramatically lower than that of AP-2. We propose that during coated pit formation, addition of clathrin to the growing edge at the rim of the pit releases Eps15 from AP-2.
Authentic Assessment as an Approach to Preschool Speech-Language Screening

Authentic assessment procedures have been advocated to evaluate speech and language skills of preschool children from multicultural, low-socioeconomic backgrounds. In this article we discuss our us...
Persistent rhythms of locomotion activity in the turtle Pseudemys scripta.

Abstract 1. 1. The spontaneous locomotor activity of turtles was recorded under conditions of normal daily light fluctuation and conditions of constant low illumination and relatively constant temperature. The activity of animals maintained in Faraday cages was compared with controls. 2. 2. Animals exposed to normal day-night conditions demonstrated above average activity from 0500 to 1000 hr. 3. 3. Both caged and control animals exhibited a persistent solar rhythm under constant conditions. This is some indication of a persistent lunar day rhythm. 4. 4. It is suggested that electrostatic field variation affects the lunar day cycle but not the solar day cycle.
Elucidating organ-specific metabolic toxicity chemistry from electrochemiluminescent enzyme/DNA arrays and bioreactor bead-LC-MS/MS

Human toxic responses are very often related to metabolism. Liver metabolism is traditionally studied, but other organs also convert chemicals and drugs to reactive metabolites leading to toxicity. When DNA damage is found, the effects are termed genotoxic. Here we describe a comprehensive new approach to evaluate chemical genotoxicity pathways from metabolites formed in situ by a broad spectrum of liver, lung, kidney and intestinal enzymes. DNA damage rates are measured with a microfluidic array featuring a 64-nanowell chip to facilitate fabrication of films of DNA, electrochemiluminescent (ECL) detection polymer [Ru(bpy)2(PVP)10]2+ {(PVP = poly(4-vinylpyridine))} and metabolic enzymes. First, multiple enzyme reactions are run on test compounds using the array, then ECL light related to the resulting DNA damage is measured. A companion method next facilitates reaction of target compounds with DNA/enzyme-coated magnetic beads in 96 well plates, after which DNA is hydrolyzed and nucleobase-metabolite adducts are detected by LC-MS/MS. The same organ enzymes are used as in the arrays. Outcomes revealed nucleobase adducts from DNA damage, enzymes responsible for reactive metabolites (e.g. cyt P450s), influence of bioconjugation, relative dynamics of enzymes suites from different organs, and pathways of possible genotoxic chemistry. Correlations between DNA damage rates from the cell-free array and organ-specific cell-based DNA damage were found. Results illustrate the power of the combined DNA/enzyme microarray/LC-MS/MS approach to efficiently explore a broad spectrum of organ-specific metabolic genotoxic pathways for drugs and environmental chemicals.
Ground-state degeneracy of the fractional quantum Hall states in the presence of a random potential and on high-genus Riemann surfaces

The fractional quantum Hall (FQH) states are shown to have q\ifmmode \tilde{}\else \~{}\fi{} $^{\mathit{g}}\mathrm{fold}$ ground-state degeneracy on a Riemann surface of genus g, where q\ifmmode \tilde{}\else \~{}\fi{} is the ground-state degeneracy in a torus topology. The ground-state degeneracies are directly related to the statistics of the quasiparticles given by \ensuremath{\theta}=p\ifmmode \tilde{}\else \~{}\fi{}\ensuremath{\pi}/q\ifmmode \tilde{}\else \~{}\fi{}. The ground-state degeneracy is shown to be invariant against weak but otherwise arbitrary perturbations. Therefore the ground-state degeneracy provides a new quantum number, in addition to the Hall conductance, characterizing different phases of the FQH systems. The phases with different ground-state degeneracies are considered to have different topological orders. For a finite system of size L, the ground-state degeneracy is lifted. The energy splitting is shown to be at most of order ${\mathit{e}}^{\mathrm{\ensuremath{-}}\mathit{L}/\ensuremath{\xi}}$. We also show that the Ginzburg-Landau theory of the FQH states (in the low-energy limit) is a dual theory of the U(1) Chern-Simons topological theory.
Combining Dynamic Stretch and Tunable Stiffness to Probe Cell Mechanobiology In Vitro

Cells have the ability to actively sense their mechanical environment and respond to both substrate stiffness and stretch by altering their adhesion, proliferation, locomotion, morphology, and synthetic profile. In order to elucidate the interrelated effects of different mechanical stimuli on cell phenotype in vitro, we have developed a method for culturing mammalian cells in a two-dimensional environment at a wide range of combined levels of substrate stiffness and dynamic stretch. Polyacrylamide gels were covalently bonded to flexible silicone culture plates and coated with monomeric collagen for cell adhesion. Substrate stiffness was adjusted from relatively soft (G9=0.3 kPa) to stiff (G9=50 kPa) by altering the ratio of acrylamide to bis-acrylamide, and the silicone membranes were stretched over circular loading posts by applying vacuum pressure to impart near-uniform stretch, as confirmed by strain field analysis. As a demonstration of the system, porcine aortic valve interstitial cells (VIC) and human mesenchymal stem cells (hMSC) were plated on soft and stiff substrates either statically cultured or exposed to 10% equibiaxial or pure uniaxial stretch at 1Hz for 6 hours. In all cases, cell attachment and cell viability were high. On soft substrates, VICs cultured statically exhibit a small rounded morphology, significantly smaller than on stiff substrates (p,0.05). Following equibiaxial cyclic stretch, VICs spread to the extent of cells cultured on stiff substrates, but did not reorient in response to uniaxial stretch to the extent of cells stretched on stiff substrates. hMSCs exhibited a less pronounced response than VICs, likely due to a lower stiffness threshold for spreading on static gels. These preliminary data demonstrate that inhibition of spreading due to a lack of matrix stiffness surrounding a cell may be overcome by externally applied stretch suggesting similar mechanotransduction mechanisms for sensing stiffness and stretch.
Iterative signal-order and noise estimation for multivariate data

The iterative order and noise (ION) estimation algorithm estimates the signal order of multivariate data, e.g. using a scree plot, and the unknown noise variances, e.g. using the expectation-maximisation (EM) algorithm. These estimates improve principal component analyses, linear regression, and Wiener filtering.
Examining the Emergence of Hybrid IS Governance Solutions: Evidence From a Single Case Site

The prior IS literature points to the importance of organizational context for predicting a firm's IS governance solution. However, for the most part this literature assumes that firms adopt a uniform IS governance solution for all business units and that this solution can be predicted by context variables at the overall organization level. The purpose of this study is to increase our knowledge about why firms implement a hybrid IS governance solution in which a subset of IS functions that includes systems development is decentralized to some business units, but not to other business units, in the same enterprise. A theoretical framework of context variables at the business unit level is first developed. An embedded, single case study provides an initial test of eight propositions derived from the framework, as well as an opportunity for theory building. Data are collected utilizing both deductive and inductive methods from IS and non-IS executives of a divisionalized Fortune 500 firm in which a uniform decentralized solution for systems development in place for almost a decade has recently been replaced by a hybrid solution. The case study findings suggest that a configuration of four variables characterizes a business unit context conducive to decentralized systems development governance organic decision-making, high business unit autonomy, a differentiation competitive strategy, and an unstable industry environment. As predicted, however, the influence of these variables is likely to be overridden and a “deviant” solution adopted when deficiencies in IT capabilities are perceived and there is a culture that supports structural change at the business unit level. Additional interview and survey data collected from the key stakeholders are then analyzed in order to develop a richer understanding of the dimensions of the IT capabilities construct at the business unit level. The notion of absorptive capacity provides a theoretical argument for the emergent findings. Implications for researching today's increasingly complex IS governance forms are then drawn.