cssi/SciSciGPT-SciSciNet huggingface dataset:
356-P: Population Pharmacokinetic Modeling of Dasiglucagon in Subjects with Type 1 Diabetes Mellitus

To quantify the impact of subject covariates on pharmacokinetics (PK) of the novel, ready-to-use glucagon analog dasiglucagon, we developed a population PK model. Dasiglucagon pharmacokinetics was dose linear in the tested dose range (0.1 to 1.0 mg) and described by a 1-compartment model with first-order absorption and elimination, including an absorption lag time and standard allometric scaling by body weight. The final model included injection site, age as covariates on bioavailability, and MDRD eGFR and sex as covariates on apparent clearance and absorption rate constant, respectively. The model also accounted for reduced drug content at end of shelf-life storage. Based on visual predictive checks the model reliably predicted observed data. The effect of covariates on dasiglucagon exposure measured by area under the concentration time curve (AUC) are shown in the figure below (predicted [95% CI]). AUCs are relative to the AUC predicted for a typical subject aged ≥ 24 years, weighing 78 kg with normal kidney function (eGFR 95 mL/min/1.73m2) and receiving a 0.6 mg dose of dasiglucagon in the abdomen. The model-predicted effects of PK covariates on dasiglucagon AUC generally fell within the observed AUC from the analysis population receiving 0.6 mg dasiglucagon (red markers, median, and 5th-95th percentile interval, n = 321) and observed across the trials to result in reliable recovery from hypoglycemia. Disclosure C. B. Knudsen: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Novo Nordisk A/S, Stock/Shareholder; Self; Zealand Pharma A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A. H. Valeur: Employee; Self; Zealand Pharma A/S. S. Maarbjerg: Employee; Self; Zealand Pharma A/S, Employee; Spouse/Partner; Zealand Pharma A/S, Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S. P. Diderichsen: Consultant; Self; Boehringer Ingelheim International GmbH, Zealand Pharma A/S, Employee; Self; Certara Netherlands bv. H. Witjes: Employee; Self; Certara.
Second Endorsements Deserve a Second Look

Although second endorsements on forged checks and money orders are common document examination problems, the question of simulation (or other forgery) of such signatures is not common. Presented are several handwriting cases in which certain questioned second endorsements would appear routinely identifiable. However, upon closer examination, the evidence supports a qualified opinion.
Outcome of less than or equal to 800-gram birth weight infants.

In Reply.— We welcome the comments of Drs Kilbride and Daily, former teachers of Dr Hoffman. As survival of extremely low birth weight infants has increased, 1 more attention has been focused on neurodevelopmental morbidity trends in this birth weight group. Conclusions are hampered by the small numbers in follow-up studies, the lack of standardization of confounding variables across different study sites, and the continuing changes and improvements in prenatal, perinatal, and neonatal care. Drs Kilbride and Daily9s early study period, 1980 to 1982, is later than the study period of Dr Bennett et al, 2 1977 to 1980.
The Impact of Cyclone Fanele on a Tropical Dry Forest in Madagascar

Cyclones, which change tree communities and alter forest structure, are thought to have had a significant selective pressure on the flora and fauna of Madagascar. Very little information, however, is available on the actual impact of cyclones on Malagasy ecosystems. On 21 January 2009, Cyclone Fanele made landfall on the western coast of Madagascar with sustained winds of 185âkm/h. We examined the immediate effects of the cyclone on tropical dry forest structure in the Kirindy Mitea National Park. In July and August 2009, we measured the height, diameter at breast height (dbh), and damage for 1361 trees in nine 25 A 25âm plots. We found that: (1) over 95 percent of trees experienced some sort of damage, including 8.8 percent mortality; (2) understory and emergent trees experienced significantly higher mortality than canopy trees; and (3) stem density was reduced 9.2Â±4.5 percent and biomass was reduced 13.4Â±8.1 percent after the cyclone. Dbh was the best predictor of trunk damage and mortality. This extensive alteration of forest structure will have a substantial shortâ and longâterm impact on the biotic communities of western Madagascar.
Control, Performance and Applications of Antagonist Actuated Manipulator Joints

Antagonist actuated joints are defined as being driven by a pair of opposing actuators, as in the arrangement of muscles in human joints. A simple method of controlling the motion and varying the compliance of the joint is presented, along with examples of the performance of a prototype joint. The use of antagonist actuators to reduce the size, inertia and backlash of manipulator arm joints is discussed. An antagonist actuated joint is one that is driven by a pair of opposing uni-directional actuators rather than by a single bi-directional actuator. This arrangement is necessary in human limbs since muscles can apply force in contraction only.
Kinetics of Thermal Death of Bacteria

Experimental observations on thermal injury and death of bacteria in the stationary phase can be explained by assuming that death results from inactivation of (XL) of N critical sites. It is assumed: (i) that inactivation of individual sites occurs at random and follows first-order kinetics, (ii) that the critical sites are identical and of equal heat resistance, and (iii) the bacterial population is homogeneous in heat resistance. A method is described for calculating k (the rate constant for inactivation of individual sites), N (sites per cell), and XL (the number which must be inactivated to cause death under the experimental conditions used) from experimental data. Theoretical curves calculated by using this model are identical with experimental curves, providing support for the assumptions used. Calculated values of N and XL were 130 and 21.7 for Pseudomonas viscosa and 175 and 2.7 for Salmonella anatum. There is considerable uncertainty in the absolute values of N, but they are probably > 100. It is predicted that XL will vary depending on the recovery medium used after heating. This theory is consistent with all experimental observations on thermal injury and death of bacteria.
Redshift-space bias and β from the halo model

We analyse scale dependence of redshift-space bias b and β ≡ Ωm0.6/b in the context of the halo model. We show that linear bias is a good approximation only on large scales, for k 0.1 h Mpc−1. Most problematic are galaxies predominantly found in groups and clusters, such as bright, red or elliptical galaxies, where we find poor convergence to a constant bias or β even on large scales.
Robotic Radiosurgery with Beams of Adaptable Shapes

In radiosurgery, a moving beam of radiation acts as an ablative surgical instrument. Conventional systems for radiosurgery use a cylindrical radiation beam of fixed cross-section. The radiation source can only be moved along simple standardized paths. A new radiosurgical system based on a six degree-of-freedom robotic arm has been developed to overcome limitations of conventional systems. We address the following question: Can dose distributions generated by robotic radiosurgery be improved by using non-cylindrical radiation beams of adaptable cross-section? Geometric methods for planning the shape of the beam in addition to planning beam motion are developed. Design criteria considered in this context are: treatment time, radiation penumbra as well as transparency of interactive treatment planning. An experimental evaluation compares distributions generated with our new radiosurgical system using cylindrical beams to distributions generated with beams of adaptable shapes.
Community-Based Organizations and Institutional Work in the Remote Rural West

The institutional landscape for public land management in the U.S. West underwent a seismic shift in the 1990s as the long-dominant resource extraction paradigm was replaced by the ecosystem management paradigm. Here we analyze the efforts of community-based organizations (CBOs), entities that emerged in some locations across the West to help their respective communities navigate the transition from resource extraction to environmental stewardship. Despite their formal status as civil society actors, in practice CBOs came to fill various institutional gaps by taking on roles traditionally assigned to both the state and the private sector. We use a case study approach to examine how the Hayfork, California–based Watershed Research and Training Center engages in institutional work within a setting that is at once both open and constrained, as the rural community within which it operates lacks strong state- or industry-led development trajectories while remaining constrained by the legacies of past institutions.
Analysis of laminar flow and heat transfer between a stationary and a rotating disk

L AMINAR flow and heat transfer between a stationary and a rotating disk has been analyzed numerically. The fluid enters the domain through a circular opening in the center of the stationary disk and flows radially outward. Unlike most of the earlier analyses, which were of the boundary-layer type, the present study deals with the solution of the complete Navier-Stokes equations and the prediction of the entire recirculating flow. Results show that, in the presence of rotation, the flow is indeed quite complex and is characterized by recirculating zones near the inlet and the exit.
The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression.

Although most studies of progesterone receptors (PR) and their two isoforms, PR-A and PR-B, focus on transcriptional stimulation, the receptors exhibit important inhibitory properties.Autoinhibition refers to an inhibitory function located in the PR N terminus, whose deletion increases transcriptional activity at least 6–10-fold. Transrepression refers to the ability of PR-A to suppress the transcriptional activity of PR-B and other nuclear receptors, including estrogen receptors.Self-squelching refers to the observation in transient transfection assays that increasing receptor concentrations paradoxically decrease transcriptional activity. Using a series of N-terminal deletion mutants constructed in both PR isoforms, we have mapped their autoinhibitory and transrepressor activities to a small ubiquitin-like modifier (SUMO-1) protein consensus-binding motif,387IKEE, located in the N terminus upstream of AF1. Self-squelching does not involve this site. SUMO-1 binds PR covalently at 387IKEE, but only if the C-terminal, liganded, hormone-binding domain is also present. A single point K388R mutation within the 387IKEE motif in either PR-A or PR-B leads to a loss of autoinhibitory and transrepressor functions of the liganded, full-length receptors. We conclude that autoinhibition and transrepression involve N-terminal sumoylation combined with intramolecular N/C-terminal communication.
One hundred times the intended dose of caudal clonidine in three pediatric patients.

Summary We report three sequential cases in which children received 100 times the intended dose of clonidine in their single shot caudals. Although all experienced excessive somnolence for up to 24 h, none had respiratory depression, oxygen desaturation, supplemental oxygen requirement, or hemodynamic instability. These cases suggest a large margin of safety exists for caudally administered clonidine in healthy children.
Approximate implementation in the absence of externalities and aggregate feasibility constraints

Abstract This note shows that in environments without externalities or aggregate feasibility constraints, extremely simple mechanisms can be used to approximately (‘virtually’) implement social choice functions in iteratively strictly undominated strategies.
974 COLOSTRAL CELLS: IgA RELKASE STIMULATED DURING PHAGOCYTOSIS

Human milk leukocytes contain large quantities of IgA and other proteins. During prolonged in vitro incubation, the IgA is released. To further examine the potential role of this process in delivering these proteins to the recepient infant, the effect of phagocytosis upon the release of IgA from colostral leukocytes was investigated. Washed leukocytes were incubated with live Escherichia coli or heat-killed Candida albicans in the presence or absence of serum opsonins. The degree of phagocytosis was determined microscopically. Controls were incubated without particles. After 15, 30, and 60 minutes, cells and supernatant fluids were recovered and assayed for total IgA and SIgA by a quantitative immunofluorescence assay. The degree of IgA release was enhanced (approximately 40%) with cells exposed to opsonized organisms, as compared to preparations containing no particles. The degree of decrease in the IgA level in the cell lysates was paralleled by an increase in IgA in the supernatant fluids from the cell preparations. In contrast, little release occurred (approximately 4%) with unopsonized organisms. The enhanced release was evident within 15 minutes. Cells incubated with opsonized organisms at 4°C did not release IgA until warmed. The enhanced release of IgA by colostral leukocytes during phagocytosis may be part of a mechanism to deliver IgA antibodies to the site of microbial colonization or infection in the infant.
Improved Methodology for Threshold Detection Studies in Asthmatic Children

Abstract This paper reports the differences between two methodologies for threshold detection of added resistive loads in children and adolescents. The first-generation apparatus utilized a series of laminar flow screens to present various total resistances, while in the second generation the apparatus utilized a servo-controlled cone that occluded an aperture to varying degrees. Protocol modifications in the second generation methodology included forced choice, attentional enhancements, and larger increments of added resistance. Two studies conducted 2 years apart provided data on the first and second generations of methodology. All participants in Study 1 (N = 33) and Study 2 (N = 33) were children with asthma. Subjects were matched for both age and asthma severity. Results showed the methodologic improvements in the second generation to be significant. Tracking and random thresholds were achieved by 85% and 82% of the subjects in Study 2 compared to 76% and 42% in Study 1, respectively. The correlation...
Productivity and Nutritive Quality of Johnsongrass (Sorghum halepense) as Influenced by Commercial Fertilizer, Broiler Litter, and Interseeded White Clover (Trifolium repens)

In the southeastern USA, there is an abundance of broiler litter from commercial poultry production that is available for use as fertilizer, but cropland and pastureland amended with broiler litter often exhibit greatly increased soil-test P. We evaluated productivity and nutritive quality of Johnsongrass (Sorghum halepense) that was interseeded with or without white clover (Trifolium repens) and which commercial fertilizer (ammonium nitrate and diammonium phosphate) or broiler litter was applied on the basis of soil-test P; broiler litter was supplemented with ammonium nitrate to be isonitrogenous with commercial fertilizer. Forage dry matter yield and foliar concentrations of crude protein, cell wall constituents, P, K, and Cu were not different among fertilizer treatments, and concentration of Zn was only slightly greater for forage amended with broiler litter than commercial fertilizer. Results indicate that broiler litter can be a cost-effective alternative to commercial fertilizer for warm-season forage production when applied on the basis of soil-test P.
High-yield maize with large net energy yield and small global warming intensity

Addressing concerns about future food supply and climate change requires management practices that maximize productivity per unit of arable land while reducing negative environmental impact. On-farm data were evaluated to assess energy balance and greenhouse gas (GHG) emissions of irrigated maize in Nebraska that received large nitrogen (N) fertilizer (183 kg of N⋅ha−1) and irrigation water inputs (272 mm or 2,720 m3 ha−1). Although energy inputs (30 GJ⋅ha−1) were larger than those reported for US maize systems in previous studies, irrigated maize in central Nebraska achieved higher grain and net energy yields (13.2 Mg⋅ha−1 and 159 GJ⋅ha−1, respectively) and lower GHG-emission intensity (231 kg of CO2e⋅Mg−1 of grain). Greater input-use efficiencies, especially for N fertilizer, were responsible for better performance of these irrigated systems, compared with much lower-yielding, mostly rainfed maize systems in previous studies. Large variation in energy inputs and GHG emissions across irrigated fields in the present study resulted from differences in applied irrigation water amount and imbalances between applied N inputs and crop N demand, indicating potential to further improve environmental performance through better management of these inputs. Observed variation in N-use efficiency, at any level of applied N inputs, suggests that an N-balance approach may be more appropriate for estimating soil N2O emissions than the Intergovernmental Panel on Climate Change approach based on a fixed proportion of applied N. Negative correlation between GHG-emission intensity and net energy yield supports the proposition that achieving high yields, large positive energy balance, and low GHG emissions in intensive cropping systems are not conflicting goals.
Estimation of the molecular weights of the multiple components of growth hormone and prolactin.

The molecular weights of growth hormone and prolactin from 5 species were determined by disc electrophoresis. Human, bovine, ovine and murine (rat and mouse) hormones were studied. The method permitted simultaneous evaluation of the molecular weight of the principal component, the aggregated forms and the deamidated modifications. For ovine, bovine and murine growth hormones, an extrapolation to infinite dilution was required to obtain a minimum molecular weight. Concentration-dependent association effects were eliminated if the maleylated derivatives were used. This assured a minimum molecular weight but the multiple components could not be distinguished. Human growth hormone and the prolactins did not exhibit the association phenomenon during electrophoresis. The molecular weights in general agreed quite well with reported values but the method tended to give values that were slightly higher than those found by ultracentrifugation, especially in the case of bovine growth hormone. (Endocrinology 85: 465,...
Evolutionary data visualization

Given data points that sample an unknown function in one independent variable, techniques are described and illustrated that generate additional data points `similar to' the given points. These techniques are optimal in two key respects. First, each technique models the data using a continuous family of functions, where each function is the smoothest possible in that energy is minimized. Here energy is a linear combination of lack-of-smoothness (defined as integrated squared second derivative of the function) and lack-of-fit (defined as sum squared deviation of the function from either the given points or the given points displaced to intersect their least squares line). Second, many members of the family compete in a robust evolutionary process to acquire energy, and the result of this competition determines the relative contribution of each member function. The techniques model the given points in that they yield probability density functions of the dependent variable for any value of the independent variable. Thus they enable the implementation of many pattern recognition and data visualization procedures.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Effect of moisture, microwave heating, and live steam treatment on phospholipase D activity in soybeans and soy flakes

The impact of enzyme activity on the nonhydratable phospholipid content of crude soybean oil has been evalu­ ated. A radiochemical method was used to assay phos­ pholipase D activity in whole and flaked soybeans stored under a variety of storage and enzyme inactivating con­ ditions. The crude enzyme was isolated and incubated with a mixture of 14C-Iabeled and unlabeled phospha­ tidylcholine. The amount of liberated radioactive choline was used as a measure of enzyme activity. Whole soy­ beans with moisture contents of 8-18% were stored at 40°C and sampled weekly for up to four weeks. Although the enzyme was active in all samples, the optimum moisture content for enzyme activity was about 14%. Flaking and flake thickness were shown to increase phospholipas D activity. At moisture levels above 10%, flakes at .012" showed about twice the activity of whole beans. As flake thickness was increased, enzyme activ­ ity decreased. Whole soybeans with moisture contents of 12-18% were treated by microwave heating under controlled condi­ tions. During the early stages of heating, the enzyme was activated, and then was gradually destroyed by the time the temperature of the beans reached 115-120°C. Approx­ imately 8-10 min of microwave heating was required to completely destroy enzymatic activity. The inactivation of phospholipase D in soyflakes treated with live steam was also evaluated. The enzyme is rapidly destroyed at temperatures of about 110°C. Evaluations of flakes sub­ jected to live steam and whole beans treated by micro­ wave heating to inactivate phospholipase D suggest that heat, moisture and enzyme activity are important factors contributing to the formation of nonhydratable phospho­ lipid in extracted crude oils.
Effectively Presenting Call Path Profiles of Application Performance

Call path profiling is a scalable measurement technique that has been shown to provide insight into the performance characteristics of complex modular programs. However, poor presentation of accurate and precise call path profiles obscures insight. To enable rapid analysis of an execution's performance bottlenecks, we make the following contributions for effectively presenting call path profiles. First, we combine a relatively small set of complementary presentation techniques to form a coherent synthesis that is greater than the constituent parts. Second, we extend existing presentation techniques to rapidly focus an analyst's attention on performance bottlenecks. In particular, we (1) show how to scalably present three complementary views of calling-context-sensitive metrics; (2) treat a procedure's static structure as first-class information with respect to both performance metrics and constructing views; (3) enable construction of a large variety of user-defined metrics to assess performance inefficiency; and (4) automatically expand hot paths based on arbitrary performance metrics --- through calling contexts and static structure --- to rapidly highlight important program contexts. Our work is implemented within HPCToolkit, which collects call path profiles using low-overhead asynchronous sampling.
Microwave spectra of 1-fluoronaphthalene and 2-fluoronaphthalene

Abstract The microwave spectra of gaseous 1-fluoronaphthalene and 2-fluoronaphthalene have been measured using three different Fourier transform microwave spectrometers in the frequency range of 1.8–10 GHz, with substantial improvements in resolution over previous measurements. The measurements include 15 a-dipole and 15 b-dipole transitions for 1-fluoronaphthalene and 12 a-dipole and 16 b-dipole transitions for 2-fluoronaphthalene. Analysis of measured lines for 1-fluoronaphthalene has yielded ground state rotational constants of A = 1920.581(2) MHz, B = 1122.2370(5) MHz, and C = 708.4819(3) MHz. Analysis of the 2-fluoronaphthalene spectra has yielded rotational constants of A = 2844.761(2) MHz, B = 808.1592(8) MHz, and C = 629.5032(3) MHz. Calculated (G09) rotational constants are in very good agreement with measured values.
Application of quantitative structure activity relationship (QSAR) models to predict ozone toxicity in the lung.

The sequence of events leading to ozone-induced airway inflammation is not well known. To elucidate the molecular and cellular events underlying ozone toxicity in the lung, we hypothesized that lipid ozonation products (LOPs) generated by the reaction of ozone with unsaturated fatty acids in the epithelial lining fluid and cell membranes play a key role in mediating ozone-induced airway inflammation. To test our hypothesis, we ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and generated LOPs. Confluent human bronchial epithelial cells were exposed to the derivatives of ozonized POPC—9-oxononanoyl, 9-hydroxy-9-hydroperoxynonanoyl, and 8-(5-octyl-1,2,4-trioxolan-3-yl-)octanoyl—at a concentration of 10 μM, and the activity of phospholipases A2 (PLA2), C (PLC), and D (PLD) was measured (1, 0.5, and 1 h, respectively). Quantitative structure–activity relationship (QSAR) models were utilized to predict the biological activity of LOPs in airway epithelial cells. The QSAR results showed a strong correlation between experimental and computed activity (r = 0.97, 0.98, 0.99, for PLA2, PLC, and PLD, respectively). The results indicate that QSAR models can be utilized to predict the biological activity of the various ozone-derived LOP species in the lung. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 441–448, 2005.
The Bush soul: Travelling consciousness in an unreal world

Abstract This paper describes a software system called “Emergence” that displays three‐dimensional, computer generated environments and autonomous, animated characters, in real‐time. The users, or participants, are represented as ‘avatars’. Through a scripting language one can use techniques of Artificial Life to specify behaviours and relationships between characters and objects. This system allows for the creation of multi‐participant virtual worlds that are ‘alive’, responsive and interactive. We examine the role of the avatar and the relationships between the avatar and its human counterpart as well as relationships between avatars and artificial life forms.
Relative Motion and Autonomous Rendezvous in Keplerian Elliptic Orbits

In this paper, the analytical closed-form solution of the Tschauner-Hempel equations that are used for rendezvous in elliptic orbits are studied and exploited. The solution is based on a state transition matrix that is completely explicit in time. Autonomous guidance algorithms to approach, to flyaround, and to depart from a target vehicle in elliptic orbits are exploited based on that solution. The algorithms are general and able to translate the chaser vehicle in any direction, decelerate while approaching the target vehicle, and accelerate when moving away. These guidance algorithms are based on the glideslope used in the past for rendezvous and proximity operations of the Space Shuttle with other vehicles. The algorithms are applied to the problem of terminal rendezvous near any Keplerian elliptic orbit in a Newtonian gravitational field showing the effects of target orbit eccentricity on the relative motion. These algorithms extend and generalize previously published solutions. Numerical simulations confirm the brevity and accuracy of the general solutions developed in the current paper.
Essential role of hypophysis in hypercorticism and hyperovarianism in DBA x CE and reciprocal mice.

SummaryWeights of the adrenals, ovaries, uteri and hypophyses of 6- to 9-month-old DBA x CE and reciprocal hybrid mice were measured in: (1) intact virgins, (2) neonatal castrates, (3) mice hypophysectomized at weaning, and (4) hypophysectomized castrates. There was marked reduction in size of the adrenals, ovaries and uteri in the hypophysectomized intact animals and of adrenals and uteri in the hypophysectomized castrates. Since at 6 to 9 months of age intact mice of these hybrid strains exhibit spontaneous enlargement of ovaries and hyperplasia of the reproductive tract, and animals ovariectomized neonatally exhibit hyperplasia of adrenals and hormonal stimulation of the reproductive tract, the present data provide definitive evidence of the essential role of the hypophysis in these hypercortical and hyperovarian syndromes.
Unique morphogenesis in Saccharomyces cerevisiae strain GS1731

During the lag and early exponential phase of growth, 50–60% of budded cells of Saccharomyces cerevisiae strain GS1731 were multiply budded. During subsequent culture growth, the frequency of multiply budded cells decreased until by stationary phase multiply budded cells were rare. Data from renewed growth of a culture after hydroxyurea treatment indicated that GS1731 mother cells could assemble up to three pre-bud sites and begin bud growth and development in each. Light and scanning electron microscopy showed two or three very small buds emerging simultaneously on a mother cell and either reaching full size at the same time or enlarging sequentially. Immunofluorescence studies revealed that these multiply budded cells had multiple bundles of cytoplasmic microtubules. DAPI staining of nuclei revealed that some of the unbudded mother cells were multinucleate and completed cytokinesis giving rise to normal daughter cells.
Evidence mounts that viruses drive atopic development.

Viral respiratory tract infections, especially early in life, have been associated with a markedly increased risk of both allergic disease and asthma. Although much effort has been focused on understanding this risk, themechanisms linking a viral respiratory tract infection with atopic development still have not been fully elucidated. Hypothesizing that defects in the antiviral immune response might underlie the development of postviral atopic disease, Kaiko et al explored the effect of Toll-like receptor (TLR) 7 deficiency on disease development. In the human subject much of the viral risk of atopic disease has been associated with early-life severe respiratory syncytial virus (RSV) infection. RSV is a single-stranded RNA paramyxovirus that is a human, but not rodent, pathogen. The fact that RSV is not a natural rodent pathogen raises concerns over its use in some models, primarily because RSV infection in mice does not lead to clinically severe disease. Two other single-stranded RNA paramyxoviruses that are natural rodent pathogens and do induce severe clinical disease are Sendai virus (SeV) and pneumonia virus of mice (PVM). Genetically, PVM is more closely related to RSV than SeV, and it is this virus model that Kaiko et al studied in neonatal (1-week-old) mice. Although others have documented translation of viral infection into atopic disease with the PVM model, the current study specifically examined how a genetic loss of TLR7 affected disease development. TLR7 recognizes single-stranded RNA, and therefore mice deficient in TLR7 would be predicted to have a defect in single-stranded RNA viral clearance. Indeed, in this report the authors found that loss of TLR7 was associated with an increased viral load that translated into a more pronounced asthma-like response, as characterized by a TH2 cytokine milieu, airway hyperreactivity, and tissue eosinophilia. Whether this increase in atopic disease was a direct effect of the increased viral load/infection severity was not tested. With SeV, a direct correlation was seen between severity of the illness and the development of an asthma/atopic response, and therefore it is quite likely that a similar effect occurs with PVM.
Dialogue and Community: The Ethical Claim of Tradition

The essay reconstructs an ethical approach towards history. The hermeneutic insight into the requirement for a dialogical access to the meaning of history is shown to entail an ethical dimension. The central thesis is that tradition raises an existential claim towards the interpreter that requires a dialogical recognition of the other’s expressed perspectives. The essay develops this thesis via a concept of tradition as an intersubjective community based on dialogue, which is inspired by Hans-Georg Gadamer’s reflections on the intertwinement of dialogical interpretation, tradition, and the ethical recognition of the other. The Gadamerian concept of tradition will nevertheless be radically revised so as to be suitable for historical interpretation. Dialogical recognition will now reach beyond the textual claims of linguistically raised validity claims to include an existential openness towards the other’s fully situated life-projects and narratives. The argument culminates in the introduction of an existential claim that history entails, and from there establishes a thorough rejection and critique of interpretive objectivism as well as of interpretive presentism.
The inner world of cell adhesion: integrin cytoplasmic domains

Many of the interactions between cells and their environment are mediated by the integrin family of heterodimeric transmembrane receptors. The past decade has been a broad-based effort to decipher the rules by which integrins function. Integrins bind both intracellular and extracellular ligands and thus transfer signals across the membrane in both directions. The cytoplasmic domains of these receptors play a key role in this bidirectional flow of information and in the formation of direct physical linkages between protein structures on the inside and outside of the cell.
Systematic Exploration of the Structural Features of Yatakemycin Impacting DNA Alkylation and Biological Activity

A systematic examination of the impact of the yatakemycin left and right subunits and their substituents is detailed along with a study of its unique three subunit arrangement (sandwiched vs extended and reversed analogues). The examination of the ca. 50 analogues prepared illustrate that within the yatakemycin three subunit structure, the subunit substituents are relatively unimportant and that it is the unique sandwiched arrangement that substantially increases the rate and optimizes the efficiency of its DNA alkylation reaction. This potentiates the cytotoxic activity of yatakemycin and its analogues overcoming limitations typically observed with more traditional compounds in the series (CC-1065, duocarmycins). Moreover, a study of the placement of the alkylation subunit within the three subunit arrangement (sandwiched vs extended and reversed analogues) indicates that it not only has a profound impact on the rate and efficiency of DNA alkylation but also controls and establishes the DNA alkylation selectivity as well, where both enantiomers of such sandwiched agents alkylate the same adenine sites exhibiting the same DNA alkylation selectivity independent of their absolute configuration.
Computational design of semiconductor nanostructures for optoelectronic, electronic, and thermoelectric applications

Efficient computational tools are an inherent part of the design of semiconductor nanostructures for desired electronic, thermal, or optical properties. The characteristics of nanostructures are strongly influenced by the properties of the interfaces, such as roughness, surface defects, or adsorbed charges, so a major challenge in predicting the properties of nanostructures lies precisely in capturing the complex interplay between the confined particle states and the surface condition. In this paper, I review some recent successful applications of ensemble Monte Carlo - an efficient and versatile transport simulation technique - to predict the properties and optimize the design of a wide range of realistic semiconductor nanostructures, from quantum cascade lasers to electronic devices and thermoelectrics.
Studying the S-nitrosylation of model peptides and eNOS protein by mass spectrometry

Oxidative addition of a nitric oxide (NO) molecule to the thiol group of cysteine residues is a physiologically important post-translational modification that has been implicated in several metabolic and pathophysiological events. Our previous studies have indicated that S-nitrosylation can result in the disruption of the endothelial NO synthase (eNOS) dimer. It has been suggested that for S-nitrosylation to occur, the cysteine residue must be flanked by hydrophilic residues either in the primary structure or in the spatial proximity through appropriate conformation. However, this hypothesis has not been confirmed. Thus, the objective of this study was to determine if the nature of the amino acid residues that flank the cysteine in the primary structure has a significant effect on the rate and/or specificity of S-nitrosylation. To accomplish this, we utilized several model peptides based on the eNOS protein sequence. Some of these peptides contained point mutations to allow for different combinations of amino acid properties (acidic, basic, and hydrophobic) around the cysteine residue. To ensure that the results obtained were not dependent on the nitrosylation procedure, several common S-nitrosylation techniques were used and S-nitrosylation followed by mass spectrometric detection. Our data indicated that all peptides independent of the amino acids surrounding the cysteine residue underwent rapid S-nitrosylation. Thus, there does not appear to be a profound effect of the primary sequence of adjacent amino acid residues on the rate of cysteine S-nitrosylation at least at the peptide levels. Finally, our studies using recombinant human eNOS confirm that Cys98 undergoes S-nitrosylation. Thus, our data validate the importance of Cys98 in regulating eNOS dimerization and activity, and the utility of mass spectroscopy to identify cysteine residues susceptible to S-nitrosoylation.
Quinidine Does Not Alter Antipyrine Metabolism

Quinidine has been reported to be a potent inhibitor of a specific isozyme of cytochrome P-450 (P-450db 1) that is responsible for the metabolism of a select group of drugs. In order to investigate the potential for quinidine to inhibit other isozymes of cytochrome P-450 and to assess whether or not P-450db 1 plays any role in antipyrine metabolism, we studied the effects of quinidine pretreatment on the pharmacokinetics and metabolism of antipyrine in six healthy, male volunteers. Using a randomized, crossover study design with a 2-week washout period between treatments, subjects received a single 1 gram antipyrine dose alone or with quinidine sulfate 200 mg orally every 8 hours for 24 hours prior to the dose of antipyrine and over the 48 hours following antipyrine administration. Mean serum concentrations, apparent oral clearance (1.93 +/- 0.86 vs 2.06 +/- 1.06 L/hr with quinidine) and half-life (13.5 +/- 3.3 vs 12.4 +/- 3.6 hr with quinidine) were not significantly different between the two treatments. The fraction of the administered dose recovered as antipyrine and measured metabolites (56.7% vs 59% with quinidine) as well as the recovery of each individual metabolite was not altered with quinidine pretreatment. In addition, the mean formation clearances for norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine exhibited no change between treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)
Three-dimensional gravity–capillary waves on water — Small surface tension case

Abstract This paper considers three-dimensional gravity–capillary waves on water of finite-depth, which are uniformly translating in a horizontal propagating direction and periodic in a transverse direction. The exact Euler equations are formulated as a spatial dynamic system in which the variable used for the propagating direction is a time-like variable. The existence of the solutions of the system is determined by two non-dimensional constants, the Bond number b and the Froude number F , which in turn give the number of eigenvalues on the imaginary axis of the complex plane for the corresponding linearized operator around a uniform flow. Assume that λ = F − 2 , C 1 is the curve in the ( b , λ ) -plane on which the first two eigenvalues for three-dimensional waves collide at the imaginary axis, and the intersection point of C 1 with { λ = 1 } is b 1 > 0 . In this paper, the case for 0 b b 1 and ( b , λ ) near C 1 is considered. A center-manifold reduction technique and a normal form analysis are applied to show that the dynamical system can be reduced to a system of ordinary differential equations. Using the existence of a homoclinic orbit connecting to a two-dimensional periodic (called generalized solitary-wave, thereafter) solution for the reduced system, it is shown that such a generalized solitary-wave solution persists for the original system by applying a perturbation method and adjusting some appropriate constants.
Revision of NNSA Packaging Certification Division’s Safety Guide 100 (SG-100)

The Transportation Technologies Group (TTG) of Oak Ridge National Laboratory (ORNL) is currently tasked, by National Nuclear Security Administration (NNSA) Service Center (SC), Office of technical Support (OTS), National Security Department (NSD), Packaging Certification Division (PCD), to revise the Defense Programs’ Safety Guide 100 (SG-100). SG-100, formally entitled “Design Guide for Packaging and Offsite Transportation of Nuclear Components, Special Assemblies, and Radioactive Materials Associated with the Nuclear Explosives and Weapons Safety Program” is being revised to reflect current regulations as well as to incorporate lessons learned over the past several years. SG-100 was last published in 1994 as Revision 1, and has served as the key guidance document for the development of Defense Programs’ Type B package designs as well as their testing and testing and certification. Since that time, there have been two major revisions to the U.S. packaging and transportation regulations (due to revisions to US federal regulations, IAEA guidelines, and national standards), re-engineering of the DOE establishing the semi-autonomous NNSA, as well as numerous improvements in the analytical tools and methodologies used in package design and confirmatory review. This revision to SG-100 will capture these changes as well as reflect various lessons learned from certification reviews which have taken place over the past decade. TTG has also been tasked by PCD to present a workshop based on the revised SG-100 in September 2004.Copyright © 2004 by ASME
Breaking Infinite CuI Carboxylate Helix Held by Cuprophilicity into Discrete Cun Fragments (n = 6, 4, 2) (Eur. J. Inorg. Chem. 2/2008)

The cover picture shows the cleavage of an infinite copper(I) helix into discrete Cun fragments of decreasing nuclearity (n = 6, 4, 2) as a result of the increase in temperature of the gas-phase reactions with polyarenes. Details are discussed in the article by Y. Sevryugina and M. A. Petrukhina on p. 219 ff.
Heterogeneity in Desiccated Solutions: Implications for Biostabilization

Biopreservation processes such as freezing and drying inherently introduce heterogeneity. We focused on exploring the mechanisms responsible for heterogeneity in isothermal, diffusively dried biopreservation solutions that contain a model protein. The biopreservation solutions used contained trehalose (a sugar known for its stabilization effect) and salts (LiCl, NaCl, MgCl2, and CaCl2). Performing Fourier transform infrared spectroscopy analysis on the desiccated droplets, spatial distributions of the components within the dried droplet, as well as their specific interactions, were investigated. It was established that the formation of multiple thermodynamic states was induced by the spatial variations in the cosolute concentration gradients, directly affecting the final structure of the preserved protein. The spatial distribution gradients were formed by two competing flows that formed within the drying droplet: a dominant peripheral flow, induced by contact line pinning, and the Marangoni flow, induced by surface tension gradients. It was found that the changes in cosolute concentrations and drying conditions affected the spatial heterogeneity and stability of the product. It was also found that trehalose and salts had a synergistic stabilizing effect on the protein structure, which originated from destructuring of the vicinal water, which in turn mediated the interactions of trehalose with the protein. This interaction was observed by the change in the glycosidic CO, and the CH stretch vibrations of the trehalose molecule.
Effects of No. 2 fuel oil on hatchability of marine and estuarine bird eggs.

Eggs of Louisiana herons, sandwich terns, and laughing gulls were oiled with either 0, 5, or 20 μl of No. 2 fuel oil in the field and in the laboratory. After 5 days of natural incubation, field-oiled and control eggs were opened and embryonic mortality was determined. No. 2 fuel oil produce'd 61% mortality in Louisiana heron eggs, 56% in sandwich tern eggs, and 83% in laughing gull eggs. Hatching success of artificially incubated, oiled eggs appeared to be lower than in control eggs. However, stress during shipment to the laboratory and problems within the incubator probably contributed to reduced hatchability in both groups.
The Amino Acid Requirement of Laying Hens 4. Supplying Minimal Levels of Essential Amino Acids from Natural Feed Ingredients

Abstract IT is generally accepted that the protein requirement of animals depends to a large degree upon the amino acid composition of the protein in question in relationship to the amino acid requirement (Mitchell and Block, 1946). Although there have been several recent reports on the crude protein requirement of laying hens (Carpenter et al., 1954; Miller et al., 1956; Thornton et al., 1957), heretofore no attempt has been made to meet specific amino acid levels in the rations under study. Johnson and Fisher (1958) have determined minimal levels of the essential amino acids for egg production utilizing a free amino acid diet. In the present study practical diets were formulated in which the protein containing ingredients provided as closely as possible the previously established amino acid estimates of requirement. EXPERIMENTAL 150 White Leghorn pullets which had been laying for about 2 months were randomly divided into 6 groups of 25 …
The cycloaddition of the 1,3-butadiene radical cation with acrolein and methyl vinyl ketone

The 1,3-butadiene radical cation reacts with acrolein and methyl vinyl ketone to produce ‘stable’ adducts. The nature of the reaction and the structures of the adducts were investigated by collisional activation decomposition (CAD) combined with tandem mass spectrometry (MS/MS), and also by Fourier transform mass spectrometry. The CAD spectra of gas-phase adducts were compared with those of suitable model compounds. On that basis, it was determined that the 1,3-butadiene radical cation undergoes a cycloaddition with these α,β-unsaturated carbonyl compounds. The butadiene radical cation serves as the ‘ene’, and the acrolein and methyl vinyl ketone react as dienes, forming cycloadducts having 2-ethenyl-2,3-dihydropyran radical cation structures.