cssi/SciSciGPT-SciSciNet huggingface dataset:
Lunette: A network of lunar landers for in-situ geophysical science

Abstract Over the last 3 years, a team at JPL has worked to design a new concept for a small, low cost lander applicable to a variety of in-situ lunar exploration activities. This concept, named Lunette, originated as a design which would exploit potential excess capacity of EELV launches by being compatible with the EELV Secondary Payload Adapter (ESPA). The original Lunette mission concept would have allowed up to six low cost landers to be delivered to a targeted region of the moon, with landings separated by a few km, allowing establishment of a regional network with a single, shared launch. The original concept faced limits in the extent of regional distribution of landing sites since all six landers were dependent on a single solid rocket braking motor. In the last year the Lunette team has focused on a modification of the original ESPA-based concept to a design that would allow launch of multiple individual landers (each with its own braking stage) on a single launch vehicle, where each lander would be capable of independent targeting and landing. With such an implementation, the entire lunar surface could be accessed for establishment of network nodes that could enable high priority geophysical measurements on a scale not seen since Apollo. The present paper discusses the current state of the design of the Lunette geophysical network lander, as well as describing mission design, science operations, and an innovative design solution allowing the lander to take critical data continuously, even over the lunar night, without the need for radioisotope power systems.
Delineation of Preferred‐Flow Paths by Response to Transient Lagoon Exfiltration

Observations of hydraulic head response to lagoon leakage into an extremely heterogeneous aquifer allow qualitative identification of spatial patterns in heterogeneity. In a 150–hour leakage experiment over such an aquifer, the fluid mass balance was estimated using a stage-fluctuation model while transient response was observed in downgradient wells and springs. Based on timing with respect to pond leakage, water-level response at different locations within the aquifer may be identified as either within or outside the influence of preferred-flow paths (PFPs). Flows at springs 150–200 m from the pond increased by 20–60% above baseline flows, showing initial increase within ca. 40 hours. Synoptic water-level rise patterns observed during the test describe enlargement of a recharge mound from beneath the pond and suggest the spatial pattern of PFPs to > 150 m distant. An analytical model assuming homogeneity (Hantush, 1967), applied to water-level response for wells > 30 m from the pond, overestimated K by > 1 order of magnitude in comparison to slug-test estimates. This discrepancy is attributed to the inferred presence of linearly continuous heterogeneities causing preferential flow. Large-scale hydraulic tests such as this sample the spatial structure for conductive pathways and may be of utility in parameterization of numerical flow models. In contrast, slug-test results give local parameter estimates, but more limited information on PFP distribution.
Statistical theory for the kinetics and dynamics of roaming reactions.

We present a statistical theory for the effect of roaming pathways on product branching fractions in both unimolecular and bimolecular reactions. The analysis employs a separation into three distinct steps: (i) the formation of weakly interacting fragments in the long-range/van der Waals region of the potential via either partial decomposition (for unimolecular reactants) or partial association (for bimolecular reactants), (ii) the roaming step, which involves the reorientation of the fragments from one region of the long-range potential to another, and (iii) the abstraction, addition, and/or decomposition from the long-range region to yield final products. The branching between the roaming induced channel(s) and other channels is obtained from a steady-state kinetic analysis for the two (or more) intermediates in the long-range region of the potential. This statistical theory for the roaming-induced product branching is illustrated through explicit comparisons with reduced dimension trajectory simulation...
Parallel-Plate Conductive Electrodes for the Fabrication of Larger 2D Colloidal Photonic Crystals

A new dielectrophoretic force-induced parallel-plate assembly technique was used to achieve close-packed 2D large colloidal photonic crystals on gold electrodes (∼200 nm thick). The electrodes were patterned on a glass substrate using a conventional UV lithography technique. The experimental tests conducted with 5.3 μm carboxyl functionalized polystyrene particles at various ac and dc voltages, frequencies, and particle concentrations showed that larger size (0.25×3 mm2) colloidal photonic crystals were fabricated on the ground electrode rather than on the working electrode. To date, this is the largest colloidal photonic crystal fabricated using this method. The reason behind this phenomenon can be attributed to the electro-osmotic flow in the colloidal system and dipole-dipole attractions between the colloidal particles.
Potential-barrier effects in photoabsorption. II. Interpretation of photoabsorption resonances in lanthanide metals at the 4d-electron threshold

The resonances in the photoabsorption spectra of the lanthanides near the $4d$ absorption edge are interpreted as transitions of the type $4{f}^{10}4{f}^{N}\ensuremath{\rightarrow}4{d}^{9}4{f}^{N+1}$. Calculations of the $4{d}^{9}4{f}^{N+1}$ energy levels and relative $\mathrm{gf}$ values for these transitions are shown to be in good agreement with the observed absorption spectra. The assumption that the lanthanides occur in trivalent form (with the exception of Eu and Yb) in the metallic solid state is confirmed by these results.
Key Role of Ubc5 and Lysine-63 Polyubiquitination in Viral Activation of IRF3

The mitochondrial antiviral signaling protein (MAVS; also known as IPS-1, VISA, and CARDIF) is essential for innate immune response against RNA viruses. MAVS transduces signals from the cytosolic RIG-I-like receptors, which bind to viral RNAs. But how MAVS activates downstream transcription factors such as IRF3 to induce type-I interferons is not well understood. We have established a cell-free system in which mitochondria derived from virus-infected cells activate IRF3 in the cytosol. Fractionation of the cytosol led to the identification of Ubc5 as a ubiquitin-conjugating enzyme (E2) required for IRF3 activation. Using an inducible RNAi strategy, we demonstrate that catalytically active Ubc5 is required for IRF3 activation by viral infection. The activation of IRF3 also requires two ubiquitin-binding domains of NEMO. Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation.
Asymmetric Dielectric Trilayer Cantilever Probe for Calorimetric High-Frequency Field Imaging

Multimaterial, microelectromechanical systems-based cantilever probes were developed for high-frequency magnetic field imaging. The basic configuration of the probe consists of a cantilever beam fabricated using surface micromachining and bulk micromachining techniques with dielectric silicon nitride and silicon oxide materials on a silicon wafer. A gold patterned metallization at the tip of the cantilever provides a source of eddy current heating due to the perpendicular component of the high-frequency magnetic field. This thermally absorbed power is converted to mechanical deflection by a multimaterial trilayer cantilever system. The deflection is measured with a beam-bounce optical technique employed in atomic force microscopy systems. We discuss the modeling, design, fabrication, and characterization of these field imaging probes
The thermodynamic properties of 2-aminobiphenyl

Measurements leading to the calculation of the ideal-gas thermodynamic properties for 2-aminobiphenyl are reported. (The Chemical Abstracts name and registry number are; [1,1′-biphenyl]-2-amine and [90-41-5].) Experimental methods included combustion calorimetry, adiabatic heat-capacity calorimetry, comparative ebulliometry, inclined-piston gauge manometry, and differential-scanning calorimetry (d.s.c.). Standard entropies, enthalpies, and Gibbs energies of formation were derived for the gas for selected temperatures between 298.15 K and 800 K. The critical temperature and critical density were determined for 2-aminobiphenyl with the d.s.c., and the critical pressure was derived. The experimental critical properties are compared with those derived from estimation methods.
Polymer crystallinity determinations by DSC

Abstract Differential scanning calorimetry (DSC) and quantitative differential thermal analysis (DTA) are widely used to determine the crystallinity of semicrystalline polymers according to the so-called “calorimetric method”. The procedure involves the determination of the heat of fusion of the polymer sample which is usually determined by measurement of the area of the melting peak above a somewhat arbitrarily interpolated baseline. In many cases the results depend strongly on the operator's estimate of the “correct” baseline position. In other cases crystallization and recrystallization effects during the heating but prior to melting render baseline methods fundamentally unsound. The theory of the calorimetric method is applied to DSC data show that simple baseline interpolation is rarely permissible in polymer heat of fusion measurements, and a generally applicable procedure is suggested which involves the measurement of the total energy absorbed in the melting region.
Oxidation of N-Nitrosoalkylamines by Human Cytochrome P450 2A6 SEQUENTIAL OXIDATION TO ALDEHYDES AND CARBOXYLIC ACIDS AND ANALYSIS OF REACTION STEPS

Cytochrome P450 (P450) 2A6 activates nitrosamines, including N,N-dimethylnitrosamine (DMN) and N,N-diethylnitrosamine (DEN), to alkyl diazohydroxides (which are DNA-alkylating agents) and also aldehydes (HCHO from DMN and CH3CHO from DEN). The N-dealkylation of DMN had a high intrinsic kinetic deuterium isotope effect (Dkapp ∼ 10), which was highly expressed in a variety of competitive and non-competitive experiments. The Dkapp for DEN was ∼3 and not expressed in non-competitive experiments. DMN and DEN were also oxidized to HCO2H and CH3CO2H, respectively. In neither case was a lag observed, which was unexpected considering the kcat and Km parameters measured for oxidation of DMN and DEN to the aldehydes and for oxidation of the aldehydes to the carboxylic acids. Spectral analysis did not indicate strong affinity of the aldehydes for P450 2A6, but pulse-chase experiments showed only limited exchange with added (unlabeled) aldehydes in the oxidations of DMN and DEN to carboxylic acids. Substoichiometric kinetic bursts were observed in the pre-steady-state oxidations of DMN and DEN to aldehydes. A minimal kinetic model was developed that was consistent with all of the observed phenomena and involves a conformational change of P450 2A6 following substrate binding, equilibrium of the P450-substrate complex with a non-productive form, and oxidation of the aldehydes to carboxylic acids in a process that avoids relaxation of the conformation following the first oxidation (i.e. of DMN or DEN to an aldehyde).
The effects of guanidine compounds on the activation of human plasminogen by streptokinase and on the rates of hydrolysis of p-toluenesulfonyl-L-arginine methyl ester by plasmin and Activator

Summary 1. Because p -toluenesulfonyl- L -arginine methyl ester precipitates streptokinase and makes it unable to activate human plasminogen, guanidino compounds were tested to see whether they reacted with streptokinase, inhibited the activation process, or had any effects on the hydrolysis of TAME by plasmin (EC 3.4.4.14) or by Activator (plasmin plus 5000 units/ml streptokinase). All experiments were performed at 37° in 0.25 M Tris buffer (pH 8.0). No evidence was found for a reaction between these compounds and streptokinase, but they inhibited the activation process while not interfering with the formation of Activator. In addition, they produced complicated effects on the hydrolysis of TAME by plasmin, similar to those reported for 6-amino-caproic acid. 2. The effects of the compounds on the rates of hydrolysis of TAME by plasmin depended upon how the experiments were performed so that 1,1-dimethyl and methyl guanidine sulfates either inhibited or accelerated the rates and 4-guanidino-butyric acid, 6-aminocaproic acid and the other guanidino compounds either had no effect or had acceleratory effects. These results were interpreted as being due to a stabilizing reaction of the compounds with plasmin and this was shown to occur by measuring the ability of both plasmin and Activator to hydrolyze TAME after they were kept in the presence or absence of 0.05 M methyl or dimethyl guanidine sulfate or 0.1 M concentrations of the other compounds for 24 h at 37° (pH 8.0). 3. The ability of the compounds to stabilize plasmin was roughly of the same order as their ability to inhibit the activation of plasminogen. In low concentrations 6-aminocaproic acid was the most potent inhibitor and stabilizer but in higher concentrations dimethyl guanidine and 4-guanidinobutyric acid were equally potent. This concentration effect was explained as due to the different equilibrium constants for the reactions of plasmin with each compound. It was suggested that the compounds also react with Activator and with plasminogen and in all of these ways interfere with the activation process.
Filament Assembly by Phosphofructokinase-1, the Gatekeeper of Glycolysis

The cytoskeleton is conventionally viewed as being composed of three filamentous networks; microfilaments, microtubules, and intermediate filaments. This view is challenged by the findings that metabolic enzymes can form filaments with structural functions. We report that phosphofructokinase-1 (PFK1), the first rate-limiting step of glycolysis, assembles into filaments in vitro and in cells. Transmission electron microscopy (TEM) showed that purified liver PFK1 is mainly tetrameric and occasionally formed short filaments in the absence of substrate. Adding the substrate fructose 6-phosphate (F6P) induced the assembly of predominantly long filaments measuring up to 250 nm. PFK1 filaments were less rigid than actin polymers, displaying right angles in contiguous assemblies. The filaments were composed of individual tetramers and had a uniform 11 nm width, resembling an organized addition of subunits forming polymers. Regulated assembly into filaments was also indicated by light scattering measurements that showed a rapid substrate-dependent increase in scattering followed by a stable plateau. Increased light scattering was blocked by excess ATP, which inhibits PFK1 activity. To further confirm activity-dependent filament assembly we generated an inactive but tetrameric liver PFK1 mutant, His199Tyr, and found that in the presence of F6P it does not form filaments, as determined by TEM, or show an increase in light scattering. To assess filament formation by PFK1 in cells, we expressed GFP-tagged PFK1 and used live-cell imaging to examine GFP-PFK1 dynamics. Confocal microscopy reveled that cytosolic PFK1 was recruited to the distal margin of lamellipodia that were devoid of mitochondria. TIRF microscopy reveled that GFP-PFK1 formed dynamic punctae. These data indicate that active but not inactive PFK1 assembles into tetramer-aligned filaments. The activity-dependent recruitment and assembly of PFK1 filaments at the plasma membrane could provide a scaffolding and structural framework for localized ATP production in lamellipodia that lack mitochondria.
hCB2 Ligand-Interaction Landscape: Cysteine Residues Critical to Biarylpyrazole Antagonist Binding Motif and Receptor Modulation

The human cannabinoid 2 GPCR (hCB2) is a prime therapeutic target. To define potential cysteine-related binding motifs critical to hCB2-ligand interaction, a library of hCB2 cysteine-substitution mutants and a novel, high-affinity biarylpyrazole hCB2 antagonist/inverse agonist (AM1336) functionalized to serve as a covalent affinity probe to target cysteine residues within (or in the microenvironment of) its hCB2 binding pocket were generated. The data provide direct experimental demonstration that both hCB2 TMH7 cysteines [i.e., C7.38(284) and C7.42(288)] are critical to optimal hCB2-AM1336 binding interaction and AM1336 pharmacological activity in a cell-based functional assay (cAMP formation). Elongating the AM1336 aliphatic side chain generated another novel hCB2 inverse agonist that binds covalently and selectively to C7.42(288) only. Identification of specific cysteine residues critical to hCB2 ligand interaction and function informs the structure-based design of hCB2-targeted medicines.
A 2,500-year history of anoxia and eutrophication in Chesapeake Bay

Ongoing monitoring programs and historical data are not sufficient to establish anthropogenic effects on the ecology of Chesapeake Bay. However, stratigraphic records preserved in the sediments can be used to reconstruct both prehistoric and historic sedimentation and water conditions of the bay, including anoxia and eutrophication. Pollen, diatoms, total organic carbon (TOC), nitrogen, total sulfur, and an estimate of the degree of pyritization of iron (DOP) are being used as paleoecological indicators in dated sediment cores for the purpose of reconstructing a long-term environmental history of the bay. Analysis of the data indicates that sedimentation rates, anoxic conditions, and eutrophication have increased in the Chesapeake Bay since the time of European settlement. For example, since initial land clearance around 1760, sedimentation rates have increased from as low as 0.02 cm yr−1 to an average 0.22 cm yr−1, and TOC from 0.14 mg cm−2 yr−1 to a high 4.96 mg cm−2 yr−1. Diatom community structure shows a steady decrease in overall diversity since 1760 and the centric:pennate ratio has increased significantly since 1940.
Pediatric Blunt Solid Organ Injury: Beyond the APSA Guidelines

The APSA guidelines were published in 2000 making nonoperative management of pediatric blunt liver and spleen injury standard for most injured children. A review of recent literature supports significant changes in management of children with liver, spleen, as well as kidney injury. Of the >300 articles on pediatric abdominal injury since the publication of the APSA guidelines, no randomized controlled trials have been conducted. Six prospective studies, however, have been completed, and several large database studies add significant insights into our understanding of pediatric spleen, liver, and kidney injury. Significant decreases in use of resources can be safely applied to children with hemodynamic stability at presentation. Recent studies suggest management based on physiologic criteria rather than injury grade may result in improved resource utilization through shortened hospitalization, abbreviated periods of bedrest, decreased use of intensive care units, earlier return to school, fewer tests, and a lower transfusion threshold. New algorithms are now available to assist in management.
Amyloid Structures from Alzheimer’s Disease Patients

Lu and colleagues report the structures of β-amyloid fibrils seeded from the brain extracts of two Alzheimer’s disease patients, a game-changing study that could open new avenues for structure-based design of diagnostic imaging agents and aggregation inhibiting drugs.
Detection of Nanometer-Scale Mixing in Phosphate-Glass/Polyamide-6 Hybrids by 1H−31P NMR

The size of phosphate-glass (Pglass) particles dispersed in a polyamide-6 (PA6) matrix by melt blending has been characterized by 1H−31P solid-state nuclear magnetic resonance (NMR). 1H spin diffusion from ∼75% of the 1H in the glass to the polyamide is observed within 50 ms, indicating proximity on a 30 nm scale. Fast dephasing of a quarter of the 31P magnetization by dipolar couplings to polyamide protons in 31P{1H} heteronuclear recoupling with dephasing by strong homonuclear interactions of protons (HARDSHIP) NMR shows that ∼25% of the Pglass is within 0.5 nm from the polyamide. This is confirmed by 1H−31P heteronuclear correlation NMR spectra with inverse T2,H filtering, which document relatively fast (1 ms) cross polarization from PA6 protons, identified by their upfield chemical shift and short transverse relaxation time T2,H, to a significant fraction of 31P in the glass. The 31P spectrum associated with the polyamide 1H reveals that the phosphate sites near the polyamide matrix are chemically alt...
Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase *

Although Parkinson disease (PD) is a progressive neurodegenerative disorder, available animal models do not exhibit irreversible neurodegeneration, and this is a major obstacle in finding out an effective drug against this disease. Here we delineate a new irreversible model to study PD pathogenesis. The model is based on simple castration of young male mice. Levels of inducible nitric-oxide synthase (iNOS), glial markers (glial fibrillary acidic protein and CD11b), and α-synuclein were higher in nigra of castrated male mice than normal male mice. On the other hand, after castration, the level of glial-derived neurotrophic factor (GDNF) markedly decreased in the nigra of male mice. Accordingly, castration also induced the loss of tyrosine hydroxylase-positive neurons in the nigra and decrease in tyrosine hydroxylase-positive fibers and neurotransmitters in the striatum. Reversal of nigrostriatal pathologies in castrated male mice by subcutaneous implantation of 5α-dihydrotestosterone pellets validates an important role of male sex hormone in castration-induced nigrostriatal pathology. Interestingly, castration was unable to cause glial activation, decrease nigral GDNF, augment the death of nigral dopaminergic neurons, induce the loss of striatal fibers, and impair neurotransmitters in iNOS−/− male mice. Furthermore, we demonstrate that iNOS-derived NO is responsible for decreased expression of GDNF in activated astrocytes. Together, our results suggest that castration induces nigrostriatal pathologies via iNOS-mediated decrease in GDNF. These results are important because castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study PD-related nigrostriatal pathologies, paving the way for easy drug screening against PD. Background: Developing a simple irreversible animal model to study nigrostriatal pathologies is important for Parkinson disease (PD). Results: Castration induces glial activation and death of dopaminergic neurons in wild type, but not iNOS−/−, young male mice. Conclusion: Castration induces nigrostriatal pathologies via iNOS. Significance: Castrated male mice may be used as a simple, toxin-free, nontransgenic, and irreversible animal model for PD.
Recombinant human antibody single chain variable fragments reactive with Candida albicans surface antigens

A combinatorial phage display library expressing human immunoglobulin heavy and light chain variable regions was used to identify phage clones capable of binding to the surface of Candida albicans blastoconidia. Single chain antibody variable fragments (scFv) derived from three clones detected C. albicans antigens by indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and Western blotting. The antigens detected were conserved among different strains of C. albicans and several other Candida species. Two scFv clones detected antigens specifically expressed by C. albicans blastoconidia; the third detected antigens in both blastoconidia and filamentous forms of C. albicans. The antigens containing the epitopes recognized by all three scFv could be extracted from blastoconidia by dithiothreitol, suggesting attachment to the cell wall via sulfhydryl bonds. Epitope detection by the scFv was sensitive to treatment of C. albicans blastoconidia with sodium periodate, but not proteinase K, indicating the cognate epitopes were composed of carbohydrate. Antigenic determinants for each of the three scFv were detected by immunohistochemical staining of skin sections from a model of cutaneous candidiasis, demonstrating expression in vivo. Through selection for the ability to bind intact organisms, the phage display system provides a means to rapidly identify monoclonal binding ligands to Candida surface antigens. Being entirely human, mature antibodies generated from the scFv have potential utility in the treatment of candidiasis.
Comments on Models and Managers: The Concept of a Decision Calculus

Managerial models for practice have undergone remarkable growth in the past 50 years. My paper on decision calculus, published in 1970, was both a progress report and a prescription for improvement. This commentary describes why I wrote the paper, my perception of why it has been considered influential, and a brief overview of what has happened since. The overview starts by tracing the trends and ideas of the 1960s into the 1970s. The 1970s blend easily into the era of decision support systems (DSS). Starting late in the decade and still continuing, DSSs have evolved rapidly due to an explosion of data, increased computer power, and advances in modeling methods. I review highlights of this evolution from the point of view of managerial models, giving special emphasis to marketing, since that has been my window on this world. The good news is that more managers than ever are using models. The bad news is that many managers do not even realize they are using models! (But we should ask whether this is really bad.) The commentary concludes with thoughts about the future of managerial models. The selection of my paper as one of the most influential in the first 50 years of Management Science was a significant honor for which I am grateful. I take it as an indication by the members of INFORMS of the importance to our field of the issues addressed.
USO DE METODOS COMPLEMENTARIOS DE APRENDIZAJE ANATOMOCLINICO EN LA DOCENCIA DE LA NEUROANATOMIA PARA LA CARRERA DE MEDICINA

Durante las ultimas decadas se ha ido produciendo una paulatina y permanente disminucion de las horas de docencia directa de los distintos cursos de anatomia para la Carrera de Medicina. Sin embargo, cada vez se requiere una mejor formacion basica para poder interpretar toda la gama de imagenologia de aplicacion clinica, ademas de la constante reiteracion por parte de los docentes clinicos respecto de la necesidad de que los estudiantes tengan los conocimientos anatomicos adecuados para ser aplicados en cada una de las diversas disciplinas clinicas. Tratando de complementar estos dos aspectos, durante los ultimos tres anos hemos desarrollado un programa de seminarios de temas anatomicos con aplicacion clinica, para cuya realizacion los estudiantes deben obtener informacion bibliografica y de docentes clinicos, recopilar grupalmente los antecedentes obtenidos, elaborar un informe escrito y exponer ante sus pares un resumen breve, claro y conciso de los distintos temas tratados. Como una forma de reforzar el aprendizaje para lograr fijacion de conceptos de los distintos seminarios se elaboran preguntas, las cuales son aplicadas en las evaluaciones globales de termino de la respectiva unidad tematica. Con el interes de comprobar las bondades del sistema y a objeto de verificar si el aprendizaje es similar entre los expositores y los auditores de los diferentes temas anatomo-clinicos, hemos analizado la totalidad de las preguntas de respuesta breve basadas en seminarios y aplicadas en la prueba integral de la asignatura de Neuroanatomia. Al comparar las respuestas correctas de los distintos grupos de seminaristas respecto de resto de sus companeros, se aprecian diferencias porcentuales significativas (83%-63,7%), diferencia que se confirma, con leves variables porcentuales, al analizar en forma particular las distintas preguntas. Pese a ser necesario recopilar mas informacion para determinar una validez definitiva del metodo, ademas de requerir la aplicacion de una encuesta para obtener la opinion de los estudiantes respecto de su utilidad, creemos que el sistema de seminarios puede ser uno mas de los diferentes metodos que permitan hacer mas atractivos los distintos temas anatomicos y lograr desde los primeros anos una valoracion de la disciplina como pilar basico de la Medicina
Recent Advances in Reduced-Order Modeling and Application to Nonlinear Computational Aeroelasticity

Reduced-order models (ROMs) are usually thought of as computationally inexpensive mathematical representations that oer the potential for near real-time analysis. Indeed, most ROMs can operate in near real-time. However, their construction can be computationally intensive as it requires accumulating a large number of system responses to input excitations. Furthermore, ROMs usually lack robustness with respect to parameter changes and therefore must often be rebuilt for each parameter variation. Together, these two issues underline the need for a fast and robust method for adapting pre-computed ROMs to new sets of physical or modeling parameters. To this eect, this paper reports on recent advances in this topic. In particular, it describes a recently developed interpolation method based on the Grassmann manifold and its tangent space at a point that is applicable to structural, aerodynamic, aeroelastic and many other ROMs based on projection schemes. This method is illustrated here with the adaptation of CFD-based aeroelastic ROMs of complete fighter configurations to new values of the free-stream Mach number. Good correlations with results obtained from direct ROM reconstruction and high-fidelity linear and nonlinear simulations are reported, thereby highlighting the potential of the described ROM adaptation method for near real-time aeroelastic predictions using pre-computed ROM databases.
Solid phase synthesis of tetrahydropyrazine-2-ones by intramolecular Mitsunobu reactions

Abstract A novel route for the synthesis of tetrahydropyrazine-2-ones on solid support through intramolecular Mitsunobu reactions is reported. The syntheses employ reductive amination of commercially available amino alcohols to attach them to ArgoGel-MB-CHO resin. Amino acids are then coupled to the derivatized solid support for construction of the ring systems and a Mitsunobu reaction between the activated amino acids and amino alcohols forms the derivatized tetrahydropyrazine-2-one rings.
A Cyano-Bridged Single-Molecule Magnet: Slow Magnetic Relaxation in a Trigonal Prismatic MnMo6(CN)18 Cluster

We report the synthesis of the first well-documented example of a cyano-bridged single-molecule magnet. An assembly reaction parallel to that employed in producing the trigonal prismatic [(Me3tacn)6MnCr6(CN)18]2+ (Me3tacn = N,N‘,N‘‘-trimethyl-1,4,7-triazacyclononane) cluster affords K[(Me3tacn)6MnMo6(CN)18](ClO4)3 (1), containing an analogous molybdenum(III)-substituted cluster. Fits to the DC magnetic susceptibility and magnetization data for 1 show that the MnMo6 cluster possesses weak antiferromagnetic coupling (J = −6.7 cm-1), leading to an S = 13/2 ground state with significantly enhanced magnetic anisotropy (D = −0.33 cm-1 and E = −0.018 cm-1). Consistent with these results, AC magnetic susceptibility measurements show the molecule to exhibit slow magnetic relaxation indicative of a single-molecule magnet with an energy barrier of 10 cm-1 for spin reversal.
Optimizing organizational design in complex service delivery systems

IT service delivery becomes an increasingly challenging business as customers demand improved quality of service while providers are driven to reduce the cost of delivery. In this paper we propose a set of optimization models to recommend organizational design changes in complex service delivery systems. The optimization models take into consideration various design factors such as technology sustainability and management complexity, and provide recommendations to organizational design transformation including both customer focused design and technology focused design. We demonstrate the applicability of the proposed methodology using data from a large IT service delivery environment.
Activation of the Blue Opsin Gene in Cone Photoreceptor Development by Retinoid-Related Orphan Receptor β

Color vision requires the expression of opsin photopigments with different wavelength sensitivities in retinal cone photoreceptors. The basic color visual system of mammals is dichromatic, involving differential expression in the cone population of two opsins with sensitivity to short (S, blue) or medium (M, green) wavelengths. However, little is known of the factors that directly activate these opsin genes and thereby contribute to the S or M opsin identity of the cone. We report that the orphan nuclear receptor RORbeta (retinoid-related orphan receptor beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. RORbeta lacks a known physiological ligand and activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX), suggesting a cooperative means of enhancing RORbeta activity. Comparison of wild-type and mutant lacZ reporter transgenes showed that the RORbeta-binding sites in Opn1sw are required for expression in mouse retina. RORbeta-deficient mice fail to induce S opsin appropriately during postnatal cone development. Photoreceptors in these mice also lack outer segments, indicating additional functions for RORbeta in photoreceptor morphological maturation. The results identify Opn1sw as a target gene for RORbeta and suggest a key role for RORbeta in regulating opsin expression in the color visual system.
A hybrid synthetic pathway for butanol production by a hyperthermophilic microbe

Biologically produced alcohols are of great current interest for renewable solvents and liquid transportation fuels. While bioethanol is now produced on a massive scale, butanol has superior fuel characteristics and an additional value as a solvent and chemical feedstock. Butanol production has been demonstrated at ambient temperatures in metabolically-engineered mesophilic organisms, but the ability to engineer a microbe for in vivo high-temperature production of commodity chemicals has several distinct advantages. These include reduced contamination risk, facilitated removal of volatile products, and a wide temperature range to modulate and balance both the engineered pathway and the host׳s metabolism. We describe a synthetic metabolic pathway assembled from genes obtained from three different sources for conversion of acetyl-CoA to 1-butanol, and 1-butanol generation from glucose was demonstrated near 70°C in a microorganism that grows optimally near 100°C. The module could also be used in thermophiles capable of degrading plant biomass.
HOBBES AND TERRORISM

ABSTRACT Terrorism is perhaps the greatest challenge of the contemporary age. Of all the canonical figures in political theory, Thomas Hobbes is the most likely candidate to offer genuine insight into this problem. Yet although his analysis of the state of nature is immediately relevant to the diagnosis of this problem, his metaphysics cannot sustain his politics. His aspiration to “immutable” natural laws grounded in the universal motivation of the fear of death crumble when this fear is no longer universal. When terrorists are inspired by a religious ideology that makes them willing to die for their beliefs—and when they benefit from other asymmetries with the civilian populations against which they are arrayed—Hobbes the theorist of war and international relations becomes less relevant than Hobbes the prescriber of “rational” (fearfully pacific) human nature.
Morphological characteristics of cultured olfactory bulb cells

Cultured olfactory bulb cells from embryonic mice had ultrastructural characteristics similar to those of many cell types in the intact adult mouse olfactory bulb. Identified cultured cells included mitral/tufted cells, granule cells, short-axon cells, and fibrous and protoplasmic astrocytes. Cultured neurons were found as individual cells, clusters or aggregates. Clusters consisted of a loose array of neurons that appeared to be densely interconnected by neurites. However, few neurites or fascicles emanated from clusters to adjoining areas. Aggregates consisted of many small, usually rounded, neurons piled on top of one larger neuron, or on more than one, with typically many neurites and fascicles projecting to adjacent aggregates, clusters or individual neurons. Neurites of cultured olfactory bulb cells were well developed, and some were several millimeters long. Synapses were very prominent in these cultures, especially in aggregates, clusters, and fascicles. Electron-lucent, dense-core, and coated vesicles were present. Polarity, shape, and length of the long axis (size) of 815 cultured neurons, identified by positive anti-microtubule-associated protein 2 staining, were documented. Cultured neurons varied in size from 9 to 27 μm, with an average size of 16 μm. Elliptical bipolar (35%), triangular multipolar (21%), and round unipolar (15%) were the most common polarity/shape combinations found in culture. Multipolar, triangular, triangular multipolar, and elliptical bipolar cells increased in size with increasing age of culture. The relative proportions of triangular, multipolar, elliptical multipolar, and triangular multipolar cells decreased, whereas the relative proportions of round, unipolar, and round unipolar cells increased with increasing age of culture. These changes in population subtypes and cell size may indicate continued differentiation and maturation of cultured neurons.
A new framework for understanding IRES-mediated translation

Studies over the past 5 or so years have indicated that the traditional clustering of mechanisms for translation initiation in eukaryotes into cap-dependent and cap-independent (or IRES-mediated) is far too narrow. From individual studies of a number of mRNAs encoding proteins that are regulatory in nature (i.e. likely to be needed in small amounts such as transcription factors, protein kinases, etc.), it is now evident that mRNAs exist that blur these boundaries. This review seeks to set the basic ground rules for the analysis of different initiation pathways that are associated with these new mRNAs as well as related to the more traditional mechanisms, especially the cap-dependent translational process that is the major route of initiation of mRNAs for housekeeping proteins and thus, the bulk of protein synthesis in most cells. It will become apparent that a mixture of descriptions is likely to become the norm in the near future (i.e. m7G-assisted internal initiation).
Effect of vinblastine on neural regulation of metabolism in rat skeletal muscle

Abstract Chronic application of vinblastine, a substance known to disrupt axoplasmic flow, to nerves innervating the fast extensor digitorum longus and slow soleus muscles of the rat, produces electrophysiological signs of denervation (depolarization and extrajunctional acetylcholine sensitivity), but does not alter motor activity. We therefore examined the effects of vinblastine treatment on those metabolites and enzymes that are known to change after denervation of fast and slow skeletal muscle. A silastic cuff containing 0.1% vinblastine was placed around sciatic nerves of adult rats for 5 days. Glucose-6-P decreased 68% in the extensor, but did not change in soleus muscles. Phosphocreatine also decreased slightly, but significantly, in the extensor. Thus, intracellular levels of glucose-6-P and phosphocreatine in the extensor may be controlled, in part, by a factor (s) transported to the muscle by axoplasmic flow. Other metabolites known to change 5 days after denervation, namely glucose, glycogen, lactate, and α-ketoglutarate, were not altered in extensor and soleus muscles innervated by vinblastine-treated nerves. The activities of glucose-6-phosphate dehydrogenase and hexokinase increased in denervated extensor muscles, but not in denervated soleus muscles. Thus, metabolism in extensor muscles may be more readily altered after disruption of neural influences than is metabolism in soleus muscles. In contrast to denervation, exposure of sciatic nerves to vinblastine did not alter enzyme activities. These results provide evidence that certain metabolic processes, as well as membrane properties in skeletal muscle, are influenced by separate and distinct neural factors.
Fungiform papilla pattern: EGF regulates inter‐papilla lingual epithelium and decreases papilla number by means of PI3K/Akt, MEK/ERK, and p38 MAPK signaling

Fungiform papillae are epithelial taste organs that form on the tongue, requiring differentiation of papillae and inter-papilla epithelium. We tested roles of epidermal growth factor (EGF) and the receptor EGFR in papilla development. Developmentally, EGF was localized within and between papillae whereas EGFR was progressively restricted to inter-papilla epithelium. In tongue cultures, EGF decreased papillae and increased cell proliferation in inter-papilla epithelium in a concentration-dependent manner, whereas EGFR inhibitor increased and fused papillae. EGF preincubation could over-ride disruption of Shh signaling that ordinarily would effect a doubling of fungiform papillae. With EGF-induced activation of EGFR, we demonstrated phosphorylation in PI3K/Akt, MEK/ERK, and p38 MAPK pathways; with pathway inhibitors (LY294002, U0126, SB203580) the EGF-mediated decrease in papillae was reversed, and synergistic actions were shown. Thus, EGF/EGFR signaling by means of PI3K/Akt, MEK/ERK, and p38 MAPK contributes to epithelial cell proliferation between papillae; this biases against papilla differentiation and reduces numbers of papillae. Developmental Dynamics 237:2378–2393, 2008. © 2008 Wiley-Liss, Inc.
Dispensing picoliter droplets on substrates using dielectrophoresis

Liquid dielectrophoresis is exploited to initiate rapid, transient flow of aqueous liquids along co-planar electrodes patterned on insulating substrates. The flow induced by the non-uniform electric field leads to a new electrostatic equilibrium. A reduced-order model predicts the transient motion of the rivulet. When the field is removed, capillary instability breaks up the rivulet into regularly spaced droplets. Periodic circular bumps patterned on the structure, when spaced according to the most unstable wavelength based on Rayleigh's inviscid theory for the cylindrical liquid jet, lead to uniformly spaced and sized droplets. A correction factor, based on the dimensionless Ohnesorge number, accounts successfully for the effect of viscosity.
Ethanol-withdrawal syndrome associated with both general and localized increases in glucose uptake in rat brain.

Abstract Glucose uptake was studied in the brains of rats undergoing an overt ethanol-withdrawal syndrome by 2-deoxy- d -[14C]glucose autoradiography. In addition to a general increase in glucose uptake, localized alterations were observed in sensorimotor cortex, globus pallidus, thalamus and cerebellum. The results suggest that the ethanol-withdrawal syndrome is associated with a general increase in glucose metabolism as well as localized increases in functionally distinct regions of sensory and motor brain regions.
Deterministic walks with choice

This paper studies deterministic movement over toroidal grids (and more generally, Cayley graphs on groups), integrating local information, bounded memory and choice at individual nodes. The research is motivated by recent work on deterministic random walks, and applications in multi-agent systems. Several results regarding passing tokens through toroidal grids are discussed, as well as some open questions.
Are Sustainable Coffee Certifications Enough to Secure Farmer Livelihoods? The Millenium Development Goals and Nicaragua's Fair Trade Cooperatives

Abstract In December 2001, green coffee commodity prices hit a 30-year low. This deepened the livelihood crisis for millions of coffee farmers and rural communities. The specialty coffee industry responded by scaling up several sustainable coffee certification programs, including Fair Trade. This study uses household- and community-level research conducted in Nicaragua from 2000 to 2006 to assess the response to the post-1999 coffee crisis. A participatory action research team surveyed 177 households selling into conventional and Fair Trade markets in 2006. In an effort to dialogue with specialty coffee industry and mainstream development agencies, results are framed within the context of the United Nations Millennium Development Goals. Findings suggest that households connected to Fair Trade cooperatives experienced several positive impacts in education, infrastructure investment, and monetary savings. However, several important livelihoods insecurities, including low incomes, high emigration, and food i...
Text-based systems and information management: artificial intelligence confronts matters of scale

Many of the more ambitious goals of artificial intelligence have proved unattainable because of the failure of the many small, successful systems to scale up. The general use of technologies such as natural language interfaces and expert systems has done little to alleviate the basic difficulties and overwhelming cost of knowledge engineering. At the same time, emerging text processing techniques, including data extraction from text and new text retrieval methods, offer a means of accessing stores of information many times larger than any organized knowledge base or database. Although knowledge acquisition from text is at the heart of the information management problem, interpreting text, paradoxically, requires large amounts of knowledge, mainly about the way words are used in context. In other words, before intelligent text processing systems can be trained to mine for useful knowledge, they must already have enough knowledge to interpret what they read. The point at which there is "enough", is still a matter of debate, as no real program seems close to having enough knowledge to achieve general human-like understanding. Current research in large-scale natural language processing has come, rightly, to focus on lexical acquisition as the key to future progress. Unfortunately, the current state of the art is quite far from the recipe for acquiring knowledge about words, because it leans too heavily on resources that are available, without consideration for what is needed. >
A New Classification of Lip Zones to Customize Injectable Lip Augmentation

Objectives: To present a new classification of 15 anatomical lip zones used to direct placement of injectable fillers during lip augmentation and to evaluate the new classification's ability to cus...
Food Insecurity and Out-of-Pocket Medical Expenditures: Competing Basic Needs?

Resource-constrained families face difficult choices when attempting to meet their basic needs and enhance their health and wellness. This research investigated the relationship between a family’s efforts to access enough food and pay their medical bills through an examination of data from the Survey of Income and Program Participation. The data provided information on out-of-pocket medical expenditures and responses to an abbreviated version of the U.S. Department of Agriculture food insecurity module for nearly 50,000 people in more than 16,000 U.S. families. A two-stage probit-least squares procedure accounted for the endogeneity of food and medical care expenditures, providing insight into the decisions that families make when allocating resources to food and medical care. The results indicated that the probability of experiencing food insecurity increased as out-of-pocket medical expenditures increased. Notably, there was no evidence for the reverse relationship—food security status did not affect medical expenditures. The results suggest that programs that seek to help families reduce out-of-pocket medical costs may indirectly improve access to food and nutrition.