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Without any catalyst or pressure, bulk non-graphitizing carbon does not exhibit any change in its atomic order (or graphitize) even at 3000 °C. We propose a route for significant graphitization in polymer-derived disordered carbon materials at moderate temperatures by pre-aligning the precursor polymer chains. Accordingly, we employ a template-based fabrication process, where the capillary forces align the polyfurfuryl alcohol chains in the form of nanowires with diameter from 100–200 nm. The nanowires are pyrolyzed at temperatures ranging from 600 °C to 2000 °C and characterized with transmission electron and Raman microscopy as well as electrical conductivity measurements. The observed significant change in atomic rearrangement is explained by the alignment of precursor chains during the templated synthesis.

DNA polymerases have the venerable task of maintaining genome stability during DNA replication and repair. Errors, nonetheless, occur with error propensities that are polymerase specific. For example, DNA polymerase λ (pol λ) generates single-base deletions through template-strand slippage within short repetitive DNA regions much more readily than does the closely related polymerase β (pol β). Here we present in silico evidence to help interpret pol λ's greater tendency for deletion errors than pol β by its more favorable protein/DNA electrostatic interactions immediately around the extrahelical nucleotide on the template strand. Our molecular dynamics and free energy analyses suggest that pol λ provides greater stabilization to misaligned DNA than aligned DNA. Our study of several pol λ mutants of Lys544 (Ala, Phe, Glu) probes the interactions between the extrahelical nucleotide and the adjacent Lys544 to show that the charge of the 544 residue controls stabilization of the DNA misalignment. In addition, we identify other thumb residues (Arg538, Lys521, Arg517, and Arg514) that play coordinating roles in stabilizing pol λ's interactions with misaligned DNA. Interestingly, their aggregate stabilization effect is more important than that of any one component residue, in contrast to aligned DNA systems, as we determined from mutations of these key residues and energetic analyses. No such comparable network of stabilizing misaligned DNA exists in pol β. Evolutionary needs for DNA repair on substrates with minimal base-pairing, such as those encountered by pol λ in the non-homologous end-joining pathway, may have been solved by a greater tolerance to deletion errors. Other base-flipping proteins share similar binding properties and motions for extrahelical nucleotides.

Cardiomyocyte differentiation is a complex multistep process requiring the proper temporal and spatial integration of multiple signaling pathways. Previous embryological and genetic studies have identified a number of signaling pathways that are critical to mediate the initial formation of the mesoderm and its allocation to the cardiomyocyte lineage. It has become clear that some of these signaling networks work autonomously, in differentiating myocardial cells whereas others work non-autonomously, in neighboring tissues, to regulate cardiac differentiation indirectly. Here, we provide an overview of three signaling networks that mediate cardiomyocyte specification and review recent insights into their specific roles in heart development. In addition, we demonstrate how systems level, 'omic approaches' and other high-throughput techniques such as small molecules screens are beginning to impact our understanding of cardiomyocyte specification and, to identify novel signaling pathways involved in this process. In particular, it now seems clear that at least one chemokine receptor CXCR4 is an important marker for cardiomyocyte progenitors and may play a functional role in their differentiation. Finally, we discuss some gaps in our current understanding of early lineage selection that could be addressed by various types of omic analysis.

Children’s literature is profoundly influential in the lives of students and is widespread throughout schools, libraries, and homes. However, the field of children’s literature lacks diversity across several domains, particularly race, gender, and ability. Educators must be knowledgeable on how to use diverse children’s literature as a tool to teach about diversity, as they strive to foster inclusive classroom environments. Teachers must also design their classroom libraries with intense care so as to provide a wide-ranging selection of books to meet the needs of children’s interests and reading levels. Books are a powerful tool for development, so teachers must make conscious decisions about the materials they provide to young readers. All children deserve exposure to a wide range of books, which include characters who are both similar and different from themselves. Educators have a responsibility to expose students to diversity through a well-written selection of multifaceted children’s literature.

The emergence of techniques to study developmental processes using systems biology approaches offers exciting possibilities for the develpmental biologist. In particular cardiac lineage selection may be particularly amenable to these types of studies since the heart is the first fully functional organ to form in vertebrates. However there are many technical obstacles that need to be overcome for these studies to proceed. Here we present a brief overview of cardiomyocyte lineage deterimination and discuss how different aspects of this process either benefit from or present unique challenges for the development of systems biology approaches. Copyright © 2009 John Wiley & Sons, Inc. For further resources related to this article, please visit the WIREs website.

Composites of nanoporous carbon and single wall carbon nanotubes were heat treated in vacuum at temperatures ranging from 1200 to 2000 °C. The resultant interface between the two allotropes of carbon was characterized using high resolution transmission electron microscopy and Raman spectroscopy. At the interface between the nanoporous carbon and the nanotube, the nanotube served as a template for ordering and orientation of the normally disordered nanoporous carbon along the nanotube axis during high temperature treatment. When annealed at 2000 °C, the nanoporous carbon transformed to graphitic nanoribbon which in turn crushed the nanotube to form a nanoscale carbon “bulb”. This result is interesting since at these temperatures, the native nanoporous carbon is well known to resist ordering and is therefore referred to as being a “non-graphitizing” carbon. That the nanotube should act as a template for the incipient graphitization suggests that bonding and strength for load transfer may be developed at these interfaces.

The correct replication and repair of DNA is critical for a cell's survival. Here, we investigate the fidelity of mammalian DNA polymerase lambda (pol lambda) utilizing dynamics simulation of the enzyme bound to incorrect incoming nucleotides including A:C, A:G, A(syn):G, A:A, A(syn):A, and T:G, all of which exhibit differing incorporation rates for pol lambda as compared to A:T bound to pol lambda. The wide range of DNA motion and protein residue side-chain motions observed in the mismatched systems demonstrates distinct differences when compared to the reference (correct base pair) system. Notably, Arg517's interactions with the DNA template strand bases in the active site are more limited, and Arg517 displays increased interactions with the incorrect dNTPs. This effect suggests that Arg517 helps provide a base-checking mechanism to discriminate correct from incorrect dNTPs. In addition, we find Tyr505 and Phe506 also play key roles in this base checking. A survey of the electrostatic potential landscape of the active sites and concomitant changes in electrostatic interaction energy between Arg517 and the dNTPs reveals that pol lambda binds incorrect dNTPs less tightly than the correct dNTP. These trends lead us to propose the following order for mismatch insertion by pol lambda: A:CA:GA(syn):GT:GA(syn):AA:A. This sequence agrees with available kinetic data for incorrect nucleotide insertion opposite template adenine, with the exception of T:G, which may be more sensitive to the insertion context.

A sheep kappa cDNA probe was isolated, characterized by sequence analysis and shown to have significant sequence identity to other kappa light chains. This probe and a sheep lambda light chain probe were used to estimate the extent of various sheep immunoglobulin light chain gene loci by Southern blot analysis of genomic DNA. The results showed that the sheep has a single hybridizing kappa constant gene and three to five kappa V segment bands. Segregation of three polymorphic bands at the lambda C locus indicated that they were products of separate C segments. Restriction fragment pattern variations were obtained using light chain probes on various sheep breeds, but no pattern or individual band was characteristic for a particular breed.

Nanofibers of poly(ethyl 2-cyanoacrylate) were directly grown via a template-less vapor phase polymerization technique directly on surface modified glass substrates. Several commercially available glass slides were investigated for polymer nanofiber deposition. In addition, glass substrates were also modified in the laboratory using silanes with different functional groups. The growth of nanofibers at different relative humidities was studied using scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was found that nanofiber formation is favored when the polymerization occurs at relative humidities greater than 68%. The diameter and the number density of the nanofibers were examined in terms of the wettability of cyanoacrylate monomer on the modified glass substrates.

The type of anionic initiator used to polymerize ethyl 2-cyanoacrylate was found to influence the morphology of the polymer formed via vapor phase polymerization. Depending upon the type of initiator, polymerization of ethyl 2-cyanoacrylate resulted in either the formation of neat polymer nanofibers (∼200 nm in diameter) or thin films. Based on the classification of anions using Hard Soft Acid Base principles, we found that harder anions favored polymer film formation while softer ones favored polymer nanofibers. Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and gel permeation chromatography (GPC) were used to characterize the structure, morphology and molecular weight of the synthesized polymers, respectively. Finally, a mechanism of formation of different polymer morphologies is proposed.

A new pathway to synthesize a carbon with both nanoporosity and pre-graphitic structures has been discovered by annealing at 2000 °C a CO 2 activated, non-graphitizing, nanoporous carbon originally derived from polyfurfuryl alcohol. The activation process with CO 2 overcomes the barrier to graphitization normally present in this carbon even when treated at high temperature. Gas adsorption analysis, skeletal density measurements, X-ray diffraction, and transmission electron microscopy are utilized to probe the structure of both the non-activated and the activated carbons at 800, 1200, 1800, and 2000 °C. The influence of activation time is also examined. Prior to activation the nanopore walls are comprised of several layers of disordered graphenes. Activation eliminates the barrier to graphitization by reducing the number of layers below the limit of detection and by removing carbon material highly susceptible to oxidation. Annealing at 2000 °C of the carbon activated to 84% burnoff induces the formation of pre-graphitic domains amongst the nanoporous carbon. The (0 0 2) bands corresponding to 2 θ = 24.3°, 26°, and 26.5° are identified and assigned to amorphous, turbostratic, and graphitic morphologies. A pore volume of 0.50 cm 3 g −1 localized in pores below 2 nm in size is preserved after annealing.

The simple deletion of nucleotides is common in many organisms. It can be advantageous when it activates genes beneficial to microbial survival in adverse environments, and deleterious when it mutates genes relevant to survival, cancer or degenerative diseases. The classical idea is that simple deletions arise by strand slippage. A prime opportunity for slippage occurs during DNA synthesis, but it remains unclear how slippage is controlled during a polymerization cycle. Here, we report crystal structures and molecular dynamics simulations of mutant derivatives of DNA polymerase lambda bound to a primer-template during strand slippage. Relative to the primer strand, the template strand is in multiple conformations, indicating intermediates on the pathway to deletion mutagenesis. Consistent with these intermediates, the mutant polymerases generate single-base deletions at high rates. The results indicate that dNTP-induced template strand repositioning during conformational rearrangements in the catalytic cycle is crucial to controlling the rate of strand slippage.

Unlike some other DNA polymerases, DNA polymerase lambda (pol lambda) utilizes DNA motion and active-site protein residue rearrangements rather than large-scale protein subdomain changes to transition between its active and inactive states. Pol lambda also has an unusual error tendency to generate single-base deletions (also known as frameshift mutations) resulting from DNA template-strand slippage. An understanding of these features requires an atomic-level link between the various structures and motions involved and observed in biochemical functions. Our simulations of pol lambda ternary complexes of various 517 mutants (Lys, Glu, His, Met, and Gln) reveal discrete orientations of the 517 residue with respect to the DNA and associated interactions (mainly electrostatic) that explain the wide range ( approximately 3-8 A) of mutant-dependent DNA motion observed (Figure 2 of manuscript): (wild-type[R517K approximately R517H approximately R517Q][R517E approximately R517A approximately R517M]). This motion critically impacts stability of the ternary complex and hence drives/hampers the enzyme's catalytic cycle. In addition to pinpointing a trend for interpreting associated frameshift error rates based on template-strand stability, the close connection between DNA movement and active-site protein residue changes suggests that pol lambda's unique architecture facilitates frameshift errors because small variations in the active-site environment (e.g., orientation of 517) can have large effects on the dynamics of the ternary pol lambda complex.

Rhizoctonia solani is a nectrotrophic fungal pathogen that causes billions of dollars of damage to agriculture worldwide and infects a broad host range including wheat, rice, potato and legumes. In this study we identify wheat genes that are differentially expressed in response to the R. solani isolate, AG8, using microarray technology. A significant number of wheat genes identified in this screen were involved in reactive oxygen species (ROS) production and redox regulation. Levels of ROS species were increased in wheat root tissue following R. solani infection as determined by Nitro Blue Tetrazolium (NBT), 3,3'-diaminobenzidine (DAB) and titanium sulphate measurements. Pathogen/ROS related genes from R. solani were also tested for expression patterns upon wheat infection. TmpL, a R. solani gene homologous to a gene associated with ROS regulation in Alternaria brassicicola, and OAH, a R. solani gene homologous to oxaloacetate acetylhydrolase which has been shown to produce oxalic acid in Sclerotinia sclerotiorum, were highly induced in R. solani when infecting wheat. We speculate that the interplay between the wheat and R. solani ROS generating proteins may be important for determining the outcome of the wheat/R. solani interaction.

Porous carbons with tunable porosity and electrical conductivity have received considerable attention due to their potential application as anodes in lithium ion batteries, electrocatalysts in fuel cells, and high surface area electrodes in electrical double layer capacitors [1,2]. High porosities and surface areas are critical to the performances of these materials. Significant porosity and surface area are easily created by activation of non-graphitizing carbon, yet the material lacks in conductivity [3–5]. Whereas graphitic carbon possesses high conductivity, it strongly resists activation by traditional methods [5]. Recently graphitic carbons with controlled pore sizes have been obtained by pyrolysis of graphitizing carbon precursors deposited in mesoporous silica templates [2,6,7]. However, the preparation of carbon with nanopores, width less than 2 nm, is unattainable by this method, thus limiting its ultimate surface area, porosity, and performance. Graphitization of non-graphitizing carbon occurs in the presence of a variety metals, but the product is contaminated with the catalyst [8–11]. Stress graphitization of pure carbon has been reported at temperatures in excess of 2000 C [12,13]. Porosity is not preserved. Herein we describe the discovery of a new route to the synthesis of a pure nanoporous carbon containing pre-graphitic structures with both high surface area and high nanoand mesoporosity from the readily available polymer precursor polyfurfuryl alcohol. Nanoporous carbon (NPC) is synthesized by pyrolysis of polymers, such as polyfurfuryl alcohol (PFA). Due to its strong resistance to transformation to graphite even when annealed at temperature above 2000 C, it is classified as non-graphitizing, which was defined by Franklin [14]. This resistance is attributed to the presence of extensive cross-linking in the precursor, which creates kinetically frozen disorder through a chaotic misalignment of the graphenes in the carbon that result during pyrolysis [15– 17]. Disorder in NPC gives rise to porosity and the majority of pores are narrowly distributed in the range from 0.4 to 0.5 nm width [16,18,19]. The pore volume and surface area of NPC can be further developed by simple activation with CO2 [20,21]. We have found that the pre-graphitic ordering of PFA-derived NPC can be accomplished after CO2 treatment at 900 C, which generates activated NPC (a-NPC). The a-NPC provides an unexpected pathway to pre-graphitic carbon with nanoporosity by subsequent annealing at 2000 C. First, p-toluenesulfonic acid monohydrate (0.048 gm, Sigma–Aldrich) was dissolved in 5 ml of Triton X-100 (Sigma–Aldrich) by heating mildly. Then to this solution, 5 ml of furfuryl alcohol (99% Sigma–Aldrich) was added. The reaction mixture was stirred magnetically at 10 C. After polymerization for 48 h the product was transferred to a quartz boat and pyrolyzed under flowing argon in a quartz tube furnace. The sample was heated at a rate of 10 C min 1 to 800 C and held for 1 h. The carbon product was pure, without inorganic contaminants. It was ground and sieved to a particle size of < 38 lm. Activated NPC was prepared in a quartz tube furnace. 0.5 gm of carbon was heated to 900 C over 1 h in flowing argon. After 1 h of soak time the gas was switched to CO2 and soaked for an additional 3.5 h. The sample was cooled back to room temperature under argon. High temperature

Previous research in sports economics has looked for the presence of consumer discrimination among sports fans of professional teams and it has produced mixed results. Scully (1974a, b) found evidence to suggest that fans of Major League Baseball (MLB) clubs did engage in consumer discrimination in the 1970s, but more recent work by Sommers and Quinton (1982) found no such evidence. In this article, we present evidence that suggests that consumer discrimination persisted in MLB into the early 1990s. Specifically, our empirical work suggests that consumers in Boston, Cleveland, Houston, San Diego and Saint Louis chose to attend fewer baseball games–ceteris paribus–when the home team in these cities added Hispanic players to the roster.

The suprachiasmatic nucleus (SCN) in the hypothalamus is the site of the master circadian clock in mammals, a complex tissue composed of multiple, coupled, single-cell circadian oscillators. Mathematical modeling is now providing insights on how individual SCN cells might interact and assemble to create an integrated pacemaker that governs the circadian behavior of whole animals. In this article, we will discuss the neurobiological constraints for modeling SCN behavior, system precision, implications of cellular heterogeneity, and analysis of heterogeneously coupled oscillator networks. Mathematical approaches will be critical for better understanding intercellular interactions within the SCN.

The preparation of porous stainless steel supports was found to have a significant impact on the properties of nanoporous carbon membranes fabricated upon them. Nanofillers were incorporated into porous stainless steel supports to modify the pore structure by reducing the average pore size and porosity. Carbon membrane properties were examined as a function of support variables such as filler content, shape, size and nature of the particles. Optimum performances, in terms of the ideal selectivity ratio for oxygen to nitrogen permeances ( S O 2 / N 2 ∼ 3 – 6 ) and the oxygen permeance (10−8 mol m−2 s−1 Pa−1), were obtained when the filler completely saturated the support. This represents about a two order of magnitude improvement in oxygen permeance when compared to carbon membranes prepared on unmodified porous stainless steel supports. The origin of the improvement in the permeance is due to the formation of carbon membranes which are on average two orders of magnitude thinner than those formed on unmodified supports, i.e., the carbon membranes exists as very thin layers around and between the silica nanoparticles. A simple geometric model based on the packing of silica particles inside the porous stainless steel support is proposed to visualize and quantify this effect. The generality of the support modification concept is also demonstrated by the ability to employ different types of nanofillers and support geometries to obtain carbon membranes with high flux. Air separation experiments show that these membranes can produce both oxygen rich streams enriched to as much as 48% by volume and nitrogen rich streams enriched to over 90% by volume at reasonable operating conditions.

The pyrolysis of polyfurfuryl alcohol was studied up to 600 °C. Micropores appear in the carbon as early as 300 °C along with a significant amount of mesopores. As the pyrolysis temperature is increased, microporosity is retained, but the mesoporosity disappears. At 600 °C the material is microporous with a monodisperse pore size distribution centered at 4–5 A. Infrared, X-ray photoelectron, and nuclear magnetic resonance spectroscopies, in combination with thermogravimetric analysis provide evidence that between 300 and 400 °C, both polyaromatic domains decorated with hydrogen and oxygen (hetero) atoms and partially decomposed polymer chains coexist. The unreacted polymer and heteroatoms induce mesoporosity by buffering the micropores created by polyaromatic domains. Raising the pyrolysis above 400 °C releases the buffering material, thereby collapsing the mesopores.

The nature of conformational transitions in DNA polymerase lambda (pol lambda), a low-fidelity DNA repair enzyme in the X-family that fills short nucleotide gaps, is investigated. Specifically, to determine whether pol lambda has an induced-fit mechanism and open-to-closed transition before chemistry, we analyze a series of molecular dynamics simulations from both the binary and ternary states before chemistry, with and without the incoming nucleotide, with and without the catalytic Mg(2+) ion in the active site, and with alterations in active site residues Ile(492) and Arg(517). Though flips occurred for several side-chain residues (Ile(492), Tyr(505), Phe(506)) in the active site toward the binary (inactive) conformation and partial DNA motion toward the binary position occurred without the incoming nucleotide, large-scale subdomain motions were not observed in any trajectory from the ternary complex regardless of the presence of the catalytic ion. Simulations from the binary state with incoming nucleotide exhibit more thumb subdomain motion, particularly in the loop containing beta-strand 8 in the thumb, but closing occurred only in the Ile(492)Ala mutant trajectory started from the binary state with incoming nucleotide and both ions. Further connections between active site residues and the DNA position are also revealed through our Ile(492)Ala and Arg(517)Ala mutant studies. Our combined studies suggest that while pol lambda does not demonstrate large-scale subdomain movements as DNA polymerase beta (pol beta), significant DNA motion exists, and there are sequential subtle side chain and other motions-associated with Arg(514), Arg(517), Ile(492), Phe(506), Tyr(505), the DNA, and again Arg(514) and Arg(517)-all coupled to active site divalent ions and the DNA motion. Collectively, these motions transform pol lambda to the chemistry-competent state. Significantly, analogs of these residues in pol beta (Lys(280), Arg(283), Arg(258), Phe(272), and Tyr(271), respectively) have demonstrated roles in determining enzyme efficiency and fidelity. As proposed for pol beta, motions of these residues may serve as gate-keepers by controlling the evolution of the reaction pathway before the chemical reaction.

Silica nanoparticles were slip cast into porous stainless steel supports, which were then coated with polyfurfuryl alcohol and pyrolyzed to make nanoporous carbon membranes. The single gas permeances of the membranes formed on modified stainless steel supports were found to be between two and three orders of magnitude larger than the permeances of nanoporous carbon membranes (

The Arabidopsis (Arabidopsis thaliana) GSTF8 gene is a member of the glutathione S-transferase (GST) family whose expression is induced by defense signals, certain chemical stresses, and some pathogens. Here, we have used transgenic plants and an in vivo imaging system to demonstrate that GSTF8 expression is subject to a distinct desensitization phenomenon because prior chemical treatment significantly reduces reactivation of the GSTF8 promoter by hydrogen peroxide, auxin, and salicylic acid. A GSTF8 null line had similar desensitization properties to wild type, demonstrating that GSTF8 protein levels are not responsible for desensitization. The resulting refractory period is unusually long lasting, with full recovery taking 4 d. Expression of the GSTF8 promoter following a second treatment occurred predominantly in newly formed tissue at the root tip, suggesting that desensitization is lost upon cell division. Expression of the endogenous GSTF8 gene and another GST gene, GSTF6, is also desensitized following treatment with hydrogen peroxide. The desensitization phenomenon can be activated by a very low concentration of inducer that is not sufficient to activate the GSTF8 promoter. These results demonstrate that activation of the GSTF8 promoter is not essential for eliciting desensitization. A key promoter sequence within the GSTF8 gene, the ocs element, is also affected by desensitization. Treatment with a phosphatase inhibitor prevents desensitization of GSTF8 expression and ocs element activity, suggesting that dephosphorylation of one or more proteins is required for desensitization to occur.

We present preliminary results on an XMM-Newton observation dedicated to Post-T-Tauri (PTT) stars. We observed the visual binary 2RE J0241-53 of the Horologium association of nearby PTT stars. The XMM observations have been complemented with ground-based optical spectroscopy and photometry. Several flares have been observed. The X-ray spectrum of the brightest star during quiescence indicates a rather cool corona (with no emission at temperatures ⩾10 MK) more similar to that of the Classical T-Tauri star TW Hya (observed with Chandra and XMM-Newton) and at variance with that of another PTT Star (PZ Tel) observed with Chandra. Approximate analysis shows large Ne/Fe, N/Fe, C/Fe abundances (compared to solar photospheric values).

Visual interpretation of the building damage distribution in Bam, Iran, caused by the earthquake on 26 December 2003 has been carried out using pre- and post-earthquake QuickBird panchromatic high-resolution satellite images to produce a damage map. Two experienced interpreters carried out the assessments, and their results were compared to analyze the reasons for discrepancies likely to occur from interpretations by different interpreters. The first damage interpretation was carried out on the post-earthquake image, whereas the second interpretation compared the pre- and post-earthquake images. The analysis revealed that when using only the post-earthquake image, interpreters tend to underestimate the levels of damage, since both interpreters assigned higher damage levels when the pre- and post-earthquake image were compared than when only using the post-earthquake image. The absolute difference in the damage levels the two interpreters assigned in the post-only assessment and pre-and post-event comparison assessment remained the same.

The suprachiasmatic nuclei (SCNs) control circadian rhythms of numerous behavioral and physiological responses. In hamsters, constant light causes “splitting” of circadian rhythms, such that a single daily bout of activity separates into two components, 12 h apart, with antiphase circadian oscillations in the left and right SCN. Given the phenotypic and functional heterogeneity of the SCN, in which ventrolateral but not dorsomedial neurons are retinorecipient, we asked how these two compartments respond to the constant lighting conditions that produce splitting, using three different phase markers of neuronal activity: PER1 (Period 1), c-FOS, and pERK (phosphorylated extracellular signal-regulated kinase). We report the emergence of a coherent novel network in which each side of the SCN exhibits two antiphase oscillating subregions, here termed “core-like” and “shell-like,” in addition to the known antiphase oscillation between the right and left SCN. The novel SCN response entails a coherent rhythm in a core-like region of the SCN, which otherwise is not cycling. A mathematical model is presented, and this model interprets the observed changes in the proportion of in-phase and antiphase populations of SCN oscillators and suggests novel testable hypotheses. Finally, the functional significance of this network was explored by investigating the adjacent hypothalamus. Activation of the paraventricular nucleus is in-phase with the ipsilateral core-like SCN, whereas activation of the lateral subparaventricular zone is in-phase with the ipsilateral shell-like SCN, pointing to a multiplicity of SCN output signals. These results suggest a neural basis for internal coincidence of SCN oscillators, and a novel mechanism of plasticity in SCN neural networks and outputs.

A novel type of thin-film catalyst has been developed that combines high activity with selective transport across a micron-scale membrane film. Nanoporous carbon was used as a support for 12-tungstophosphoric acid with composite films synthesized by two distinct approaches: in-situ polymerization and adsorption from solution. Ion sputtering and XPS were used in combination to characterize the high dispersion of the catalyst within the film in the former case and a gradient in catalyst concentration in the latter. Both methods produce intact Keggin structures as demonstrated by FTIR spectroscopy. Gas permeation experiments indicate a preservation of separation capacity with O2/N2 permeability ratios as high as 6.5. The catalytic films were benchmarked using the decomposition of methyl tert-butyl ether at 55 °C and demonstrate remarkable increases in both conversion and simultaneous separation of decomposition products. Integrated conversions in a semi-batch reactor configuration far exceed the thermodynam...

This paper describes a novel robotic end-effector and a method for grasping deformable objects with undefined shapes and geometry, such as sacks and bags. The first prototype end-effector, designed for applications in the U.S. Postal Service, is comprised of two parallel rollers with gripping surfaces in which the rollers are pushed toward each other. When the end-effector comes into contact with any portion of the deformable object, the rollers turn inwardly so that a graspable portion of the object is dragged between the rollers. The rollers stop rotating when a graspable portion of the material/object is caught in between, allowing the object to be maneuvered by the robot. The object is released when the rollers turn outwardly. The end-effector described in this article can grab and hold filled sacks from any point on the sack, regardless of the sack's orientation. Experimental evaluation of the end-effector has proven the design and implementation remarkably effective. This article describes the hardware, control method, and design issues associated with the end-effector. Note to Practitioners - Delivery and postal services around the world currently use sacks to hold letters, magazines, and small boxes. The considerable weight of these sacks, their lack of handles, eyelets, or other operator interfaces, and the unpredictable shape and size of the packages within create awkward and uncomfortable handling predicaments for mail handlers at all U.S. Postal Service distribution centers. Currently, no robotic hand or end-effector is commercially available to grab and hold sacks effectively, so sacks must be handled manually by postal employees in distribution centers. This paper describes the design of a novel robotic end-effector for manipulating deformable objects with undefined shapes, such as sacks and bags. This device, which does not mimic human hand architecture, is simple and practical; it makes use of the friction between two rotating rollers to grab sack material when it is in close proximity of the end-effector. The rollers cease rotation when sufficient sack material is collected between the rollers to support the sack. They reverse their rotation, and turn outwardly to release the sack again. This end-effector is able to grab a sack at any point, does not require the edge of the sack to be gathered and flattened prior to grasp, does not require the sack to be placed on its bottom, needs no operator intervention, does not use the weight of the sack to lock and secure the sack in the end-effector, and does not damage the sack contents.

TGA/OBF family members are bZIP transcription factors that bind to the octopine synthase (ocs) element, a plant promoter sequence that has been strongly linked to defence/stress responses. Intron-containing hairpin (ihp) constructs were used to generate Arabidopsis lines with reduced expression of TGA4 and TGA5. No visible phenotypic differences were observed between ihpTGA and wild-type (WT) plants. However, the ihpTGA4 and ihpTGA5 plants had opposite affects on ocs element activity, with the ihpTGA4 lines enhancing, and the ihpTGA5 lines reducing, the response of an ocs element construct to the key defence signals, salicylic acid (SA) and H2O2, in roots.

Lung cancer is the most common cause of cancer related death in Ireland. The majority of lung cancers are inoperable at the time of diagnosis and consequently the overall 5 year survival is less than 10%. The objective of the ProActive Lung Cancer Detection (PALCAD) study was to evaluate whether low dose chest computed tomographic scanning (LDCCT) can detect early stage asymptomatic lung cancer in a high risk urban population.Four hundred and forty nine subjects of median age 55 years (range 50-74) with a median pack year smoking history of 45 years (range 10-160), with no previous cancer history and medically fit to undergo thoracic surgery were recruited. After informed consent, LDCCT was performed on all subjects. Non-calcified nodules (NCNs) of/=10 mm in diameter were referred for biopsy. Follow up with interval LDCCT at 6, 12 and 24 months to exclude growth was recommended for NCNs10 mm in diameter.Six (1.3%) NCNs of/=10 mm were detected of which one (0.23%) had non-small cell lung cancer stage 1; 145 NCNs of10 mm were detected in 87 (19.4%) subjects. Mediastinal masses were detected in three subjects (0.7%)-one small cell lung cancer and two benign duplication cysts. Incidental pathology was noted in 276 patients (61.5%), most commonly emphysema and coronary artery calcification.The prevalence of resectable lung cancer detected by LDCCT at baseline screening was low at 0.23%, but there was a high rate of significant incidental pathology.

A model for the structure of a non-graphitizing carbon is built by randomly incorporating between 0.5% and 4% non-hexagonal rings into an extended sp2 carbon sheet. The sheets are created using Cerius2 Modeling software, optimized using a DREIDING force-field, and turbostratically layered to create a three-dimensional structure. We show that the calculated pair distribution function (PDF) for models containing approximately 1% non-hexagonal rings is remarkable similar to the experimental PDF obtained from neutron scattering by a non-graphitizing carbon prepared from polyfurfuryl alcohol pyrolyzed at 1200 °C. No attempt was made to fit the model to the experimental data, and the model has no adjustable parameters except for the fraction of non-hexagonal rings.

Porous solids are of great technological importance due to their ability to interact with gases and liquids not only at the surface, but throughout their bulk. Although large pores can be produced and well controlled in a variety of materials, nanopores in the range of 2 nm and below (micropores, according to IUPAC classification) are usually achieved only in carbons or zeolites. To date, major efforts in the field of porous materials have been directed towards control of the size, shape and uniformity of the pores. Here we demonstrate that porosity of carbide-derived carbons (CDCs) can be tuned with subångström accuracy in a wide range by controlling the chlorination temperature. CDC produced from Ti3SiC2 has a narrower pore-size distribution than single-wall carbon nanotubes or activated carbons; its pore-size distribution is comparable to that of zeolites. CDCs are produced at temperatures from 200-1,200 degrees C as a powder, a coating, a membrane or parts with near-final shapes, with or without mesopores. They can find applications in molecular sieves, gas storage, catalysts, adsorbents, battery electrodes, supercapacitors, water/air filters and medical devices.

The suprachiasmatic nuclei (SCN) control circadian oscillations of physiology and behavior. Measurements of electrical activity and of gene expression indicate that these heterogeneous structures are composed of both rhythmic and nonrhythmic cells. A fundamental question with regard to the organization of the circadian system is how the SCN achieve a coherent output while their constituent independent cellular oscillators express a wide range of periods. Previously, the consensus output of individual oscillators had been attributed to coupling among cells. The authors propose a model that incorporates nonrhythmic “gate” cells and rhythmic oscillator cells with a wide range of periods, that neither requires nor excludes a role for interoscillator coupling. The gate provides daily input to oscillator cells and is in turn regulated (directly or indirectly) by the oscillator cells. In the authors' model, individual oscillators with initial random phases are able to self-assemble so as to maintain cohesive rhythmic output. In this view, SCN circuits are important for self-sustained oscillation, and their network properties distinguish these nuclei from other tissues that rhythmically express clock genes. The model explains how individual SCN cells oscillate independently and yet work together to produce a coherent rhythm.

Poly(ethylene glycol), which has a negligible carbon yield upon pyrolysis, was used as a template to study the controlled formation of mesoporosity in pyrolytic carbons. A series of carbons was produced from mixtures of poly(ethylene glycol) and poly(furfuryl alcohol) with 25, 50 and 75% composition by weight and an Mn of 300 to18 500 g/mol of template. Polydisperse dextran adsorption reveals a maximum in uptake for 8000 g/mol and 50% templated carbons, while materials from 75% mixtures or those from less than 2000 g/mol template yielded negligible dextran uptake. These results correlated well with the intensity ratio of a broad peak between 7 and 11° 2θ in the X-ray diffraction spectrum and the 002 diffraction peak and also qualitatively with micrographs of the internal microstructure of the carbons. The results suggest a templating process dominated by both the molecular size of the template and the rate of expulsion of decomposed template material during the formation of the solid.

The heart is a large organ containing many cell types, each of which is necessary for normal function. Because of this, cardiac regenerative medicine presents many unique challenges. Because each of the many types of cells within the heart has unique physiological and electrophysiological characteristics, donor cells must be well matched to the area of the heart into which they are grafted to avoid mechanical dysfunction or arrhythmia. In addition, grafted cells must be functionally integrated into host tissue to effectively repair cardiac function. Because of its size and physiological function, the metabolic needs of the heart are considerable. Therefore grafts must contain not only cardiomyocytes but also a functional vascular network to meet their needs for oxygen and nutrition. In this article we review progress in the use of pluripotent stem cells as a source of donor cardiomyocytes and highlight current unmet needs in the field. We also examine recent tissue engineering approaches integrating cells with various engineered materials that should address some of these unmet needs.

Transcriptional control of the expression of stress-responsive genes is a crucial part of the plant response to a range of abiotic and biotic stresses. Research carried out in the past few years has been productive in identifying transcription factors that are important for regulating plant responses to these stresses. These studies have also revealed some of the complexity and overlap in the responses to different stresses, and are likely to lead to new ways to enhance crop tolerance to disease and environmental stress.

Using a transient analysis of permeation, i.e. the time lag method, as a function of temperature and pressure, it is shown that each of the parameters needed to fully evaluate adsorption and diffusion can be obtained in situ. These experiments were conducted on a supported tubular nanoporous carbon membrane, 5.1 cm 2 in area and prepared by ultrasonic deposition of poly(furfuryl alcohol) onto a porous stainless steel support. The permeation experiments were conducted at temperatures ranging from 25 to 225°C and over a range of pressures from 100 to 700 kPa. Under these conditions the fluxes ranged from 10 −7 to 10 −4 mol/m 2 /s with permeances ranging between 10 −12 and 10 −9 mol/m 2 /s/Pa. Heats of adsorption were found to be 2.5, 2.21, 3.05 and 2.52 kcal/mol for N 2 , O 2, Ar and CO 2 , respectively, and generally lower than those reported for granular nanoporous carbons. The apparent activation barriers to diffusion were also found to be low at 2.06, 5.87, 4.12, 5.89 and 2.19 kcal/mol for He, N 2 , O 2 , Ar and CO 2 . These results point to the presence of two parallel pathways for transport — the major one through the nanopores but a second through a few defect pores. Assumed to be on the order of 50 nm in diameter, these defects were calculated to represent a total area fraction of 3.43×10 −9 .

A novel method for producing carbon membranes for ultrafiltration applications is presented using a spray deposition and pyrolysis of poly(furfuryl alcohol)/poly(ethylene glycol) mixtures on macroporous stainless steel supports. The poly(ethylene glycol) or PEG employed as a carbonization template creates a mesoporosity that leads to pores in the ultrafiltration range. Scanning electron microscopy (SEM) shows that the membranes consisted of 12- to 15-m thick carbon films. Gas permeation and water permeability data were used for the calculation of mean pore sizes, which were found to decrease with decreasing average molecular weight of the PEG template. Ultrafiltration of a polydisperse dextran solution was used to quantify the retention properties of the membranes. Molecular weight cutoffs determined from dextran retention data were shown to vary with template molecular weight: values of 2 × 10 4 ,3 .5 × 10 4 , and 6 × 10 4 gm ol −1 dextran were measured for respective templates of 2000, 3400, and 8000 g mol −1 PEG. For PEG molecular weights of 2000 or below, the templating effect was ill defined, membrane film cracking became more prominent, and membrane selectivity and reproducibility were adversely affected. © 2002 Published by Elsevier Science B.V.

In vivo, cardiomyocytes comprise a heterogeneous population of contractile cells defined by unique electrophysiologies, molecular markers and morphologies. The mechanisms directing myocardial cells to specific sub-lineages remain poorly understood. Here we report that overexpression of TGFβ-Activated Kinase (TAK1/Map3k7) in mouse embryonic stem (ES) cells faithfully directs myocardial differentiation of embryoid body (EB)-derived cardiac cells toward the sinoatrial node (SAN) lineage. Most cardiac cells in Map3k7-overexpressing EBs adopt markers, cellular morphologies, and electrophysiological behaviors characteristic of the SAN. These data, in addition to the fact that Map3k7 is upregulated in the sinus venous-the source of cells for the SAN-suggest that Map3k7 may be an endogenous regulator of the SAN fate.

Thermoelectric properties of single wall carbon nanotubes (SWNT) are quite sensitive to gases in contact with the tube walls. This effect makes possible a thermoelectric chemical sensor. Large, reversible swings in thermoelectric power (S), sometimes even involving sign changes in S, have been observed. Even contact of the SWNTs with He and N 2 and H 2 result in easily detectable and reversible changes in S. Smaller, polar alcohol molecules stimulate a large thermoelectric response, although H 2 O has no effect. For adsorption of six membered ring molecules C 6 H n in SWNTs, the large thermoelectric response observed for Benzene (n = 6) is seen to decrease as the π electrons in the molecule are removed, and the coupling between the molecules and the SWNT is thereby reduced. These effects are discussed in terms of the diffusion thermopower for a rope, and a new scattering channel associated with adsorbed molecules.

This study included a comparison of the baseline Sn–3.5Ag eutectic to one near-eutectic ternary alloy, Sn–3.6Ag–1.0Cu and two quaternary alloys, Sn–3.6Ag–1.0Cu–0.15Co and Sn–3.6Ag–1.0Cu–0.45Co, to increase understanding of the effects of Co on Sn–Ag–Cu solder joints cooled at 1–3 ◦ C/s., typical of reflow assembly practice. The results revealed joint microstructure refinement due to Co-enhanced nucleation of the Cu6Sn5 phase in the solder matrix, as suggested by Auger elemental mapping and calorimetric measurements. The Co also reduced intermetallic interface faceting and improved the ability of the solder joint samples to maintain their shear strength after aging for 72 h at 150 ◦ C. Some recent additional results with Co and Fe additions are consistent with this catalysis effect, where a reduced total solute level was tested. The baseline Sn–3.5Ag joints exhibited significantly reduced strength retention and coarser microstructures.

PurposeThis paper sets out to explain the new Securities and Exchange Commission Rule 15c3‐5, which will require broker‐dealers to adopt and implement risk controls to govern their provision of “direct market access” (DMA).Design/methodology/approachThe paper explains how the development and use of automated electronic trading processes and systems motivated broker‐dealers to offer DMA, “sponsored access,” and “naked access.” It explains the systems of risk management controls and supervisory procedures a broker‐dealer is required to maintain to manage the financial, regulatory, and other risks of sponsored access, including financial and regulatory controls and procedures.FindingsThe SEC proposed the Rule to more effectively manage the financial, regulatory, and other risks, such as legal and operational risks, associated with market access.Originality/valueThe paper offers practical guidance from expert broker‐dealer lawyers.

The assessment of Student Outcomes is an import component for program evaluation and improvement. Though not proposed as the only tool a program should employ to measure the achievement of outcomes, the capstone design course can be a valuable mechanism to measure performance with regards to Student Outcomes. Because of the expansive reach of the engineering design process, capstone design projects present a natural environment to structure assessment activities that directly map to Student Outcomes. This paper presents versions of the Mechanical Engineering capstone design course that have been specifically structured to assess achievement of Student Outcomes commonly included in engineering accreditation criteria. Typically the outcomes are assessed by assignments that guide the engineering design process.Copyright © 2014 by ASME

SummaryPrion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (“strains”) in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.