cssi/SciSciGPT-SciSciNet huggingface dataset:
Butyrate restores fibronectin at cell surface of transformed cells

Abstract Transformed rat kidney cells were found to produce soluble fibronectin in amounts higher than those produced by normal rat kidney cells. In spite of this, they lacked the fibrillar fibronectin network present at the surface of the normal cells. Treatment of the transformed cells with butyrate converted them into extremely flat cells with abundant fibronectin at the cell-substratum interphase. Such cells subsequently grew into monolayers with normal morphology. This was accompanied by a restoration of fibrillar fibronectin network at the cell surface.
Evolution of an octacentric isochromosome in mouse L-cells

A sub-line of mouse L-cells exhibits a rather long biarmed chromosome which shows eight C-bands. Incorporation of BrdU for less than one cell cycle results in lateral asymmetry in the pericentromeric region as well as in the two arms. These regions of asymmetry correspond to four C-banding regions in each arm. Before it is fully condensed at metaphase, and particularly upon treatment with Hoechst, this chromosome expresses eight primary constrictions. Hence it is an octacentric. Presumably, it originated from tandem rejoinings between the short arms and the long arms of four chromosomes followed by the formation of an isochromosome. Since it is present in almost 100% cells, this octacentric chromosome must divide equationally at every cell division.
A phenomenology of political apathy: Scheler on the origins of mass violence

In his criticisms of the German youth movement and the emergence of fascism across Europe during the early 1920s, Max Scheler draws a distinction between the different senses of political apathy that give rise to mass political movements. Recent studies of mass apathy have tended to treat all forms of apathy as the same and as a consequence reduced the diverse expressions of mass violence to the same, stripping mass movements of any critical function. I show in this paper that Scheler’s distinction provides the means by which to locate the various origins of mass violence and the practical means by which to address this violence that preserves the liberating potential of collective political movements.
Evolutionary biogeography on Mexico's Baja California peninsula: A synthesis of molecules and historical geology

Science progresses through a consilience of knowledge from disparate disciplines of research. Knowledge so acquired is vital to scientific growth because it provides the underpinnings for new theories and laws that transcend disciplinary boundaries and have greater universal explanatory power. What could be more disparate than the study of DNA molecules within the mitochondria of cells, and the fluctuation of sea levels and movement of crustal plates that compose the outer layers of our planet? In this issue of PNAS, Riddle et al. (1) present a thought-provoking synthesis of these disciplines through a study of mitochondrial genes across major vertebrate groups in one of the most geologically dynamic areas on Earth—the Baja California peninsula. Baja California is the second longest and most geographically isolated peninsula in the world. Over the last 4–5 million years, it has undergone a uniquely complex tectonic origin and ecological transformation. What we see today as a rugged, isolated peninsula originally was connected to the west coast of mainland Mexico but became torn away by differential movements of the Pacific and North American plates. Since then, it has rifted approximately 300 km to the northwest along what has become known as the San Andreas Fault. This separation occurred in various stages of uplift, submergence, and geographical fragmentation, leaving the peninsula an archipelago at times. This dynamic environmental history has had a profound effect on the evolution, distribution, and genetic structuring of Baja California's terrestrial vertebrates. The first major treatment of the biogeography of terrestrial vertebrates in Baja California appeared in a 1960 symposium issue of …
An analytical model of the Jovian magnetosphere

Using Euler potentials, we construct a class of axisymmetric magnetic field models that exhibit the general features of the dayside Jovian field as observed by Pioneers 10 and 11. The particular model used for illustration contains a distended, disk-like field along the equator, a blunt, earth-like magnetosphere boundary, and the possibility of multiple trapping regions along a field line. The self-consistent ring current is calculated, together with representative drift periods for energetic particles.
Pharmacokinetics of Methyprylon Following a Single Oral Dose

Single oral doses of 300 mg of methyprylon were administered to 10 healthy volunteers. Plasma concentrations of methyprylon and its dehydro metabolite were measured using a recently developed HPLC assay. Plasma concentration–time data were fitted to a two-compartment model with either first-order absorption, zero-order absorption, or two consecutive, discontinuous, first-order absorption rate constants. Based on the criteria of visual inspection, the correlation coefficient, standard deviations of the parameter estimates, and the residual sum of squares, it was concluded that the zero-order absorption model fit the data best. Mean (± SD) values for the half-life (9.2 ± 2.2 h), apparent clearance, (11.91 ± 4.42 mL/h/kg) and apparent steady-state volume of distribution, (0.97 ± 0.33 L/kg) were found.
Review article: the role of antisecretory therapy in the management of non-variceal upper gastrointestinal bleeding

Non-variceal, upper gastrointestinal bleeding accounts for 300,000 hospitalizations annually in the US and the risk of rebleeding and mortality remain high. The aim of this study was to review the incidence and causes of non-variceal upper gastrointestinal haemorrhage, criteria for early discharge, risk stratification and intravenous vs. oral proton-pump inhibitor use. Peptic ulcer disease accounts for 45% of all admissions for upper gastrointestinal bleeding. Clinical and endoscopic predictors of adverse outcome have been identified. The Rockall scoring system identifies patients who can be considered for early discharge after endoscopy. Evidence supports the use of intravenous proton-pump inhibitor therapy for patients with bleeding ulcers associated with high-risk stigmata. Patients who are clinically stable and in whom upper endoscopy has shown an ulcer with a clean base or a flat pigmented spot have a low risk for rebleeding and may be discharged early on oral proton-pump inhibitor therapy. Proton-pump inhibitor treatment reduces ulcer rebleeding but does not affect overall mortality. In the US, most patients with ulcer bleeding have low-risk stigmata, and thus, can be treated with oral proton-pump inhibitors and discharged early.
Entry preemption through capacity expansion in the U.S. titanium industry

This study investigates the impact of expected excess capacity on the probability of firm entry into a single-product oligopoly, specifically, the U.S. titanium industry. Predicted values for excess capacity as well as its components, production, and capacity are generated. By disentangling the components of excess capacity and estimating them independently, it is possible to separate incumbents' discretionary actions regarding capacity expansion, which may preempt entry, from the effects of underlying cycles in demand, which subsequently affect production. These predicted values are utilized in logit models which indicate that expected levels of capacity expansion did appear to decrease the probability of firm entry, while expected levels of production and excess capacity had no effect on the probability of entry into the U.S. titanium industry.
Purification of Recombinant Rous Sarcoma Virus Integrase Possessing Physical and Catalytic Properties Similar to Virion-Derived Integrase

Abstract Recombinant Rous sarcoma virus integrase cloned from the Prague A (PrA) virus strain was expressed inEscherichia coli.Here we report the detailed purification procedure resulting in an apparently homogeneous integrase. Recombinant PrA integrase was compared at both the protein structural and the catalytic levels to avian myeloblastosis virus integrase purified from virions. Both proteins exist minimally in a dimeric state at low nanomolar concentrations as analyzed by glycerol gradient sedimentation and protein crosslinking studies. Likewise, both proteins have similar specific activities for full-site (concerted integration reaction) and half-site strand transfer activities using linear 480-bp retrovirus-like donor substrates that contain wild-type or mutant termini. They respond similarly to high NaCl concentrations (∼350 mM) as well as aprotic solvents for efficient full-site strand transfer. The data suggest that recombinant integrase proteins with physical and catalytic properties similar to the virion counterpart can be purified using these techniques and will faithfully and efficiently promote the full-site integration reactionin vitro.
FDI Structure, Investment Specificity, and Multinationality Value under Host Market Uncertainty

To address mixed results regarding the value of multinationality, we take into account some important but less explored contingent factors related to country and subsidiary asset specificity. From our analyses using a panel dataset of Korean FDI, we find that subsidiaries’ local commitment in terms of FDI depth and local sales are negatively associated with multinationality value, whereas their intra-firm trade links to other affiliates are positively associated with the value. We conclude from our findings that in addition to dispersed operations across countries, other country- and subsidiary-specific factors moderate the effect of FDI breadth on multinationality value. We believe our study contributes to the literature by its fine-grained analysis of the environmental and organizational conditions wherein MNCs’ multinationality generates value.
Hydrogen Abstraction Followed by Nitroxide‐Mediated Polymerization: Synthesis of 2,7‐Dibromofluorene‐Labeled Polystyrene

Chromophore end-labeled polystyrene is synthesized using nitroxide-mediated polymerization (NMP) by decomposing 2-2′-azoisobutyronitrile (AIBN) or benzoyl peroxide (BPO) in the presence of fluorene or fluorene derivatives. End-labeling is dependent on the thermally produced radical species selectively abstracting a hydrogen atom from the 9-position of the fluorene species prior to initiation of styrene. From gel permeation chromatography (GPC) data and UV–Vis analysis, it is found that AIBN initiation, compared to BPO, leads to a more controlled polymerization system, producing polymers with predictable molecular weights, narrower polydispersity index (PDI) values (<1.3), and higher amounts of fluorene end-labeling. In terms of the reaction parameters, no consistent trend is observed as a function of the timing of styrene's addition or the temperature at which the hydrogen abstraction phase is performed. Analysis of the chromophore content by UV–Vis spectroscopy demonstrated that the presence of bromine atoms on the 2- and 7-position of the fluorene species leads to higher percent labeling of the chromophore species, presumably due to a more facile abstraction of the hydrogen at the 9-position.
Preparation of Pillared Clays and Their Catalytic Properties

Publisher Summary Pillared clays (PILCs) represent a new class of microporous materials that have potential for use as catalysts. A great deal of progress has been made in the understanding of these materials, particularly as relates to their catalytic behavior. Commercial applications for PILCs have been slow in coming. However, they represent a diversified range of materials with a very large number of possible variations: choice of layer, pillar, cation substitution, polymer-pillar combination, pre- and postpillaring treatments, etc. It is hard to imagine that useful applications will not arise from such a diversified class of materials. One needs to learn how to better control the synthetic process, to elucidate the structures in more detail, and to better stabilize the composites. Additionally, uses outside the field of catalysis need to be explored.
Chemokine Receptor Requirements for Epidermal T-Cell Trafficking

Inflamed skin contains CD4 T-cell subsets that express chemokine receptors CCR4, CCR6, and/or CCR10. Prior attempts to reveal the distinct role(s) of each receptor in T-cell trafficking to skin have not produced a coherent story. Different conclusions drawn by separate research groups are difficult to reconcile because of the disparate inflammation models used. Here we directly compare CD4 T cells from wild-type, CCR4−/−, CCR6−/−, and CCR10−/− mice in parallel assays of trafficking to skin. Our models require direct competition between wild-type and receptor-deficient populations for access to inflamed cutaneous sites. Major histocompatibility complex-peptide tetramers allowed us to identify antigen-specific endogenous long-term memory CD4 T cells within skin after multiple topical immunizations. We separately analyzed cells from the dermal and epidermal layers, allowing us to assess the involvement of each receptor in trafficking between dermis and epidermis. We found that CCR4 deficiency reduces accumulation of memory CD4 T cells in skin by approximately 20-fold, but neither CCR6 nor CCR10 deficiency yielded any detectable effects. Strikingly, no differences in dermal versus epidermal localization were observed for cells lacking any of these three receptors. Our findings raise the possibility that CCR6 and CCR10 play (as yet) unknown roles in cutaneous T-cell immunology, unrelated to skin-specific trafficking.
Evaluation of synthetic linear motor-molecule actuation energetics.

By applying atomic force microscope (AFM)-based force spectroscopy together with computational modeling in the form of molecular force-field simulations, we have determined quantitatively the actuation energetics of a synthetic motor-molecule. This multidisciplinary approach was performed on specifically designed, bistable, redox-controllable [2]rotaxanes to probe the steric and electrostatic interactions that dictate their mechanical switching at the single-molecule level. The fusion of experimental force spectroscopy and theoretical computational modeling has revealed that the repulsive electrostatic interaction, which is responsible for the molecular actuation, is as high as 65 kcal·mol−1, a result that is supported by ab initio calculations.
Has Public Administration Grown Up? The Road to Maturation

Abstract Public administration has not yet become adult. It exhibits many of the signs of adolescence. These signs most clearly are self-doubt and continuous adoption of the newest fad. Also the field has not come to terms with its content, so it breaks into smaller and smaller units, each with a different name considered superior to the others. Yet all have much in common. The field needs to come back together in order to move toward adulthood, which will best be realized by linking public administration and democracy. Shakespeare's call for justice seems an appropriate challenge.
Automated terrain generation using LIDAR and waterbody survey data

LIDAR data provides a dense and precise sampling of ground elevations on land, but not of bathymetric elevations in a waterway. By supplementing LIDAR data with densely interpolated waterway survey data, terrain models can be generated to approximate LIDAR-derived topography combined with waterway bathymetry. Three-dimensional interpolation techniques are used to generate a dense waterway bathymetry, as well as the bounding region to clip and fill the LIDAR data with this bathymetry. Consequently, the resulting terrain is fit for both visualization and further processing in hydraulic and hydrological models.
Protein phosphorylation in arterial muscle contracted by high concentration of phorbol dibutyrate in the presence and absence of Ca2

Abstract Porcine carotid arterial muscles were 32 P-labeled then contracted with 8 μM phorbol dibutyrate (PDBu) in normal physiological salt solution (PSS) and in Ca 2+ -free PSS containing 0.5 mM ethyene glycol-bis (β-aminoethyl ether)- N,N,N′,N′ -tetraacetate. Significant incorporation of [ 32 P]phosphate into the 20-kDa myosin light chain, a 28-kDa protein, desmin and caldesmon was measured with no apparent difference between normal and Ca 2+ -depleted muscles. Ca-determination showed that the Ca 2+ -depleted muscle contained 15% of the total Ca of the normal muscle. However, determination of the actin-bound Ca revealed that all the Ca in the Ca 2+ -depleted muscle could be accounted for by its actin-bound Ca. Accordingly, protein phosphorylation during the slow PDBu-induced contraction may proceed in the virtual absence of free Ca 2+ . Phosphopeptide mapping of the myosin light chain isolated from muscles contracted with PDBu either in the presence or absence of Ca 2+ showed that two-thirds of the incorporated [ 32 P]phosphate was attributable to myosin light chain kinase catalyzed phosphorylation and one-third was due to phosphorylation by protein kinase C. PDBu increased the phosphorylation of the 28-kDa protein, desmin and caldesmon two- to threefold, as compared with that in muscles contracted by KCl depolarization or by the receptor mediated agonists norepinephrine and histamine. Muscles contracted by high concentration of PDBu in the presence or absence of Ca 2+ could be fully relaxed and recontracted.
Using just-in-time teaching techniques in the principles of economics course

This article provides an overview of Just-in-Time Teaching (JiTT) pedagogy and the development, implementation, and assessment of JiTT pedagogy in teaching introductory, college-level economics courses. Broadly speaking, JiTT techniques blend structured, out-of-class, web-based exercises with related classroom activities that promote active student learning. The two components work together to promote a feedback loop that encourages outside-of-class preparation by students, provides prompt feedback on students' conceptual understanding of course material, and informs just-in-time modifications of class activities and discussion. The benefits of the JiTT approach can be summarized as follows: (a) Students are more likely to be prepared for class, (b) the use of student responses in class creates a positive feedback loop that promotes further learning, (c) JiTT exercises make instructors more aware of student thinking processes, and (d) JiTT pedagogy increases students' cognitive learning.
A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells

Proinflammatory T helper 1 (Th1) cells express high levels of carbohydrate ligands for the endothelial selectins, but the molecular basis for this phenotype is incompletely understood. We document here a significant role in selectin ligand formation for the recently described Th1 transcription factor T-bet. Th1 cells generated from T-bet-/- mice showed significantly lower levels of ligands for both E-selectin and P-selectin, compared with wild-type (WT) Th1 cells. Enforced expression of T-bet in WT Th0 cells only modestly up-regulated P-selectin ligands and had no effect on E-selectin ligands. To define a mechanism for the defects observed in T-bet-/- mice, we examined expression of glycosyltransferases involved in selectin ligand biosynthesis. T-bet-/- Th1 cells expressed significantly lower levels of core 2 β1,6 N-acetylglucosaminyltransferase I (C2GlcNAcT-I), but no differences in levels of α 2,3-sialyltransferase IV (ST3Gal-IV). Further, we show that T-bet is responsible for the signal transducer and activator of transcription 4 (Stat4)–independent increase in Th1 cells of fucosyltransferase VII (FucT-VII). We also identify ST3Gal-VI, which is thought to play an important role in E- and P-selectin ligand formation, as an interleukin 12 (IL-12)–regulated, T-bet–dependent gene. These data show that T-bet controls selectin ligand formation in Th1 cells via control of expression of multiple key enzymes in response to IL-12 signaling and establishes an independent transcriptional pathway for control of Th1 cell traffic.
Effect of cyanuric acid amendment on atrazine mineralization in surface soils and detection of the s-triazine ring-cleavage gene trzD

Abstract Cyanuric acid amendment was tested for potential enhancement of atrazine mineralization activity because this compound is the metabolite in the degradation pathway of s -triazines prior to ring-cleavage. The effect of cyanuric acid on: (i) subsequent atrazine mineralization kinetics and (ii) the detection of a hybridization signal to the s -triazine ring-cleavage gene trzD in surface soils with different histories of atrazine application were examined in this study. Composite soil samples from two agricultural soils and one riparian zone soil were amended with cyanuric acid. Mineralization was measured as 14 CO 2 evolution in samples spiked with [ 14 C-U-ring]-labeled atrazine. Dot-blot hybridization assays were performed on total genomic DNA extracted from the soils using the gene trzD (cyanuric acid amidohydrolase) as a probe. The source of this gene is Pseudomonas NRRLB-12228, which can cleave the s -triazine ring, but cannot grow with atrazine. The cyanuric acid amendment had a variable effect on the subsequent mineralization of atrazine in all three soils. The trzD hybridization signals in all three soils were negligible or undetectable, although parallel mineralization studies of one of the agricultural soils showed fast and extensive 14 CO 2 evolution from [ring-U- 14 C]-atrazine. The results suggest that the trzD gene, which is currently the only known s -triazine ring-cleavage gene, is not dominant among the atrazine-degrading populations of these soils.
Coupled-mode structure in oxide aperture vertical-cavity surface-emitting lasers and its effects on lasing threshold

Mode coupling caused by the presence of an oxide dielectric aperture is addressed. For rays passing through the dielectric, we apply the complex reflection coefficient that corresponds to a Fabry–Perot subcavity formed by a slab dielectric and the nearest distributed Bragg reflector (DBR) mirror. The DBR reflectivity applies to rays passing through the aperture opening. The diffraction effects for curved wave-front incidence are also included. The expansion coefficients of the cavity eigenmodes into pure Gauss–Laguerre (GL) modes are obtained for the lowest eigenmodes in the optimum waist representation. The effects of the aperture location in the cavity standing wave are addressed. Over the entire range of aperture diameters, higher cavity losses and higher threshold currents result for antinode placement, owing to wide-angle scattering. This agrees with experimental results and earlier scattering analysis by use of pure GL (uncoupled) eigenmodes. Mixing with higher modes increases round-trip losses at small apertures, compared with uncoupled-mode results. In the limit of a large aperture diameter, the cavity eigenmodes decouple to pure GL modes.
Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase inhibitors.

Janus kinases (JAK) are the mediators of a variety of cytokine signals via their cognate receptors that result in activation of intracellular signaling pathways. Alterations in JAK1, JAK2, JAK3 and TYK2 signaling contribute to different disease states, and dysregulated JAK-STAT signaling is associated with hematological malignancies, autoimmune disorders and immune-deficient conditions. Genetic alterations of JAK2 occur in the majority of patients with myeloproliferative neoplasms (MPN) and occur in a subset of patients with acute leukemias. JAK-mediated signaling critically relies on STAT transcription factors, and on activation of the MAPK and PI3K/Akt signaling axes. Hyperactive JAK at the apex of these potent oncogenic signaling pathways therefore represents an important target for small molecule kinase inhibitors in different disease states. The JAK1/2 inhibitor ruxolitinib and the JAK3 inhibitor tofacitinib were recently approved for the treatment of myelofibrosis and rheumatoid arthritis, respectively and additional ATP-competitive JAK inhibitors are in clinical development. Although these agents show clinical activity, the ability of these JAK inhibitors to induce clinical/molecular remissions in hematological malignancies appears limited and resistance upon chronic drug exposure is seen. Alternative modes of targeting JAK2 such as allosteric kinase inhibition or HSP-90 inhibition are under evaluation as is the use of histone deacetylase inhibitors. Combination therapy approaches integrating inhibition of STAT, PI3K/Akt and MAPK pathways with JAK kinase inhibitors might be critical to overcome malignancies characterized by dysregulated JAK signaling.
A Protein Molecule in a Mixed Solvent: The Preferential Binding Parameter via the Kirkwood-Buff Theory

In a recent article (Schurr, J. M., D. P. Rangel, and S. R. Aragon. 2005. A contribution to the theory of preferential interaction coefficients. Biophys. J. 89:2258–2276), a detailed derivation of an expression for the preferential binding coefficient via the Kirkwood-Buff theory of solutions was presented. The authors of this Comment (Shulgin, I. L., and E. Ruckenstein. 2005. A protein molecule in an aqueous mixed solvent: fluctuation theory outlook. J. Chem. Phys. 123:054909) also recently established on the basis of the Kirkwood-Buff theory of solutions an equation for the preferential binding of a cosolvent to a protein. There are other publications that relate the preferential binding parameter to the Kirkwood-Buff theory of solutions for protein + binary mixed solvents. The expressions derived in the two articles mentioned above are different because the definitions of the preferential binding parameter are different. However, there are articles in which the definitions of the preferential binding parameter are the same, but the derived equations that relate the preferential binding parameter to the Kirkwood-Buff integrals are different. The goal of this Comment is to examine the various expressions that relate the preferential binding parameter to the Kirkwood-Buff theory.
Rapid fabrication of nickel molds for prototyping embossed plastic microfluidic devices

The production of hot embossed plastic microfluidic devices is demonstrated in 1–2 h by exploiting vinyl adhesive stickers as masks for electroplating nickel molds. The sticker masks are cut directly from a CAD design using a cutting plotter and transferred to steel wafers for nickel electroplating. The resulting nickel molds are used to hot emboss a variety of plastic substrates, including cyclo-olefin copolymer and THV fluorinated thermoplastic elastomer. Completed devices are formed by bonding a blank sheet to the embossed layer using a solvent-assisted lamination method. For example, a microfluidic valve array or automaton and a droplet generator were fabricated with less than 100 μm x–y plane feature resolution, to within 9% of the target height, and with 90 ± 11% height uniformity over 5 cm. This approach for mold fabrication, embossing, and bonding reduces fabrication time and cost for research applications by avoiding photoresists, lithography masks, and the cleanroom.
An extended corresponding states model for the thermal conductivity of refrigerants and refrigerant mixtures

Abstract The extended corresponding states (ECS) model of Huber et al. (Huber, M.L., Friend, D.G., Ely, J.F. Prediction of the thermal conductivity of refrigerants and refrigerant mixtures. Fluid Phase Equilibria 1992;80:249–61) for calculating the thermal conductivity of a pure fluid or fluid mixture is modified by the introduction of a thermal conductivity shape factor which is determined from experimental data. An additional empirical correction to the traditional Eucken correlation for the dilute-gas conductivity was necessary, especially for highly polar fluids. For pure fluids, these additional factors result in significantly improved agreement between the ECS predictions and experimental data. A further modification for mixtures eliminates discontinuities at the pure component limits. The method has been applied to 11 halocarbon refrigerants, propane, ammonia, and carbon dioxide as well as mixtures of these fluids. The average absolute deviations between the calculated and experimental values ranged from 1.08 to 5.57% for the 14 pure fluids studied. Deviations for the 12 mixtures studied ranged from 2.98 to 9.40%. Deviations increase near the critical point, especially for mixtures.
Invited talk: Noise and mismatch in sub 28nm silicon processes

Mismatch and noise cause significant yield loss in 28nm and smaller process nodes. This paper examines these effects in analog, digital, RF and memory circuits, along with methods to quantify, account for and counteract problems associated with them.
Effects of Various Postemergence Herbicide Treatments and Tobacco Thrips (Frankliniella fusca) Injury on Peanut Yields in Virginia

Abstract A two-year field study was conducted in Virginia to determine the combined effects of earlyseason injury caused by certain postemergence-applied herbicides and tobacco thrips, Frankliniell...
Utilization of Never-Medicated Bipolar Disorder Patients towards Development and Validation of a Peripheral Biomarker Profile

There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated BPD patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD. We employed microarray technology to measure global leukocyte gene expression in first-episode (n=3) and currently medicated BPD patients (n=26), and matched healthy controls (n=25). Following an initial feature selection of the microarray data, we developed a cross-validated 10-gene model that was able to correctly predict the diagnostic group of the training sample (26 medicated patients and 12 controls), with 89% sensitivity and 75% specificity (p<0.001). The 10-gene predictor was further explored via testing on an independent cohort consisting of three pairs of monozygotic twins discordant for BPD, plus the original enrichment sample cohort (the three never-medicated BPD patients and 13 matched control subjects), and a sample of experimental replicates (n=34). 83% of the independent test sample was correctly predicted, with a sensitivity of 67% and specificity of 100% (although this result did not reach statistical significance). Additionally, 88% of sample diagnostic classes were classified correctly for both the enrichment (p=0.015) and the replicate samples (p<0.001). We have developed a peripheral gene expression biomarker profile, that can classify healthy controls from patients with BPD receiving antipsychotic or mood stabilizing medication, which has both high sensitivity and specificity. Moreover, assay of three first-episode patients who had never received such medications, to first enrich the expression dataset for disease-related genes independent of medication effects, and then to test the 10-gene predictor, validates the peripheral biomarker approach for BPD.
Chronic treatment with typical and atypical antipsychotics increases the AMPA-preferring form of AMPA receptor in rat brain

Abstract We assessed the effects of chronic (21 day) administration of antipsychotic drugs on the density of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in rat brain. We used two typical antipsychotic drugs, haloperidol and pimozide, and two atypical antipsychotic drugs, risperidone and clozapine. Antipsychotic drugs as a group significantly elevated the density of the AMPA receptor measured with an AMPA receptor agonist ([ 3 H]AMPA), but not with an AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione ([ 3 H]CNQX). In all regions studied, the magnitude of the increase seen with chronic typical antipsychotic drugs was significantly greater than that seen with chronic atypical antipsychotic drugs. In frontal cortex and striatum, typical antipsychotics but not atypical antipsychotics elevated AMPA receptor binding over control. These findings suggest that antipsychotic drugs alter the agonist affinity of the AMPA receptor without altering the number of AMPA receptors. Typical antipsychotic drugs may be more potent in this effect than atypical antipsychotic drugs, especially in critical corticostriatal circuits.
Tech-Know-Logy: Using Multimodal Simulation Strategies to Bring Data Management and Patient Care Technologies to Life

Abstract The purpose of this project was to thread patient care technology and informatics competency into immersive patient care learning experiences for undergraduate nursing. By integrating the academic overlay of a simulated electronic health record system with other simulation modalities, the University of Utah established comprehensive and dynamic learning experiences. These scenarios were introduced into first-semester courses of a baccalaureate nursing program. This multimodal method of simulation delivery resulted in immersive experiences providing meaningful context for students to learn while applying information management competencies to patient care. Many challenges remain in preparing nursing graduates to enter the workforce with the necessary informatics and patient care technology competencies. The process described here provides educators with a valuable pedagogical alternative for teaching these skills regardless of the electronic health record system employed at their academic institution.
Solution structure of a circular-permuted variant of the potent HIV-inactivating protein cyanovirin-N: structural basis for protein stability and oligosaccharide interaction.

Abstract The high-resolution solution structure of a monomeric circular permuted (cp) variant of the potent HIV-inactivating protein cyanovirin-N (CV-N) was determined by NMR. Comparison with the wild-type (wt) structure revealed that the observed loss in stability of cpCV-N compared to the wt protein is due to less favorable packing of several residues at the pseudo twofold axis that are responsible for holding the two halves of the molecule together. In particular, the N and C-terminal amino acid residues exhibit conformational flexibility, resulting in fewer and less favorable contacts between them. The important hydrophobic and hydrogen-bonding network between residues W49, D89, H90, Y100 and E101 that was observed in wt CV-N is no longer present. For instance, Y100 and E101 are flexible and the tryptophan side-chain is in a different conformation compared to the wt protein. The stability loss amounts to ∼2 kcal/mol and the mobility of the protein is evident by fast amide proton exchange throughout the chain. Mutation of the single proline residue to glycine (P52G) did not substantially affect the stability of the protein, in contrast to the finding for wtCV-N. The binding of high-mannose type oligosaccharides to cpCV-N was also investigated. Similar to wtCV-N, two carbohydrate-binding sites were identified on the protein and the Man α1→2Man linked moieties on the sugar were delineated as binding epitopes. Unlike in wtCV-N, the binding sites on cpCV-N are structurally similar and exhibit comparable binding affinities for the respective sugars. On the basis of the studies presented here and previous results on high-mannose binding to wtCV-N, we discuss a model for the interaction between gp120 and CV-N.
The role of polyfusomes in generating branched chains of cystocytes during Drosophila oogenesis.

Three-dimensional models were constructed utilizing the information gained from electron micrographs of serial sections of two clones of cystocytes undergoing their terminal divisions. In each clone a polyfusome connected all eight cystocytes together. Each of the spindles was oriented so that one pole touched the polyfusomes, while the other pointed away from it. This positioning of spindles ensures that one cell of each dividing pair retains all previously formed canals, while the other receives none. The two cells that eventually come to contain the maximum number of canals and fusomal material are the ones that differentiate as pro-oocytes, while the others become nurse cells. The orientation of each spindle suggests that the polyfusome formed at one division determines the placement of the cytoskeletal fibers that anchor the spindles formed at the next division. There is a centripetal gathering together of new canals following each cycle of cystocyte division, which is thought to result from the subsequent contraction of the polyfusomal system. Females homozygous for the otu1 mutation are characterized by ovarian tumors, which result when germarial cystocytes undergo supernumerary divisions and fail to differentiate into either nurse cells or oocytes. An analysis of electron micrographs taken of serially sectioned, mutant germaria showed that most germ cells were single or belonged to clusters of two or three interconnected cells. Therefore otu1 cystocytes are unable to undergo a sustained series of arrested cleavages. These cystocytes contain fusomal material that shows ultrastructural differences from normal polyfusomes. We conclude: (1) that a normal polyfusomal system is a necessary prerequisite for the production of a branched chain of cystocytes and for their subsequent differentiation into pro-oocytes and nurse cells; and (2) that a product encoded by the otu+ gene is essential for the construction of a functional polyfusome.
C4-Dicarboxylic acid metabolism in bundle-sheath chloroplasts, mitochondria and strands of Eriochloa borumensis Hack., a phosphoenolpyruvate-carboxykinase type C4 species.

C4-acid metabolism by isolated bundlesheath chloroplasts, mitochondria and strands of Eriochloa borumensis Hack., a phosphoennolpyruvate-carboxykinase (PEP-CK) species, was investigated. Aspartate, oxaloacetate (OAA) and malate were decarboxylated by strands with several-fold stimulation upon illumination. There was strictly light-dependent decarboxylation of OAA and malate by the chloroplasts, but the chloroplasts did not decarboxylate aspartate in light or dark. PEP was a primary product of OAA or malate decarboxylation by the chloroplasts and its formation was inhibited by 3-(3,4-dichlorophenyl)-1, 1-dimethylurea or NH4Cl. There was very little conversion of PEP to pyruvate by bundle-sheath chloroplasts, mitochondria or strands. Decarboxylation of the three C4-acids by mitochondria was light-independent. Pyruvate was the only product of mitochondrial metabolism of C4-acids, and was apparently transaminated in the cytoplasm since PEP and alanine were primarily exported out of the bundle-sheath strands. Light-dependent C4-acid decarboxylation by the chloroplasts is suggested to be through the PEP-CK, while the mitochondrial C4-acid decarboxylation may proceed through the NAD-malic enzyme (NAD-ME) system. In vivo both aspartate and malate are considered as transport metobolites from mesophyll to bundle-sheath cells in PEP-CK species. Aspartate would be metabolized by the mitochondria to OAA. Part of the OAA may be converted to malate and decarboxylated through NAD-ME, and part may be transported to the chloroplasts for decarboxylation through PEP-CK localized in the chloroplasts. Malate transported from mesophyll cells may serve as carboxyl donor to chloroplasts through the chloroplastic NAD-malate dehydrogenase and PEP-CK. Bundle-sheath strands and chloroplasts fixed 14CO2 at high rates and exhibited C4-acid-dependent O2 evolution in the light. Studies with 3-mercaptopicolinic acid, a specific inhibitor of PEP-CK, have indicated that most (about 70%) of the OAA formed from aspartate is decarboxylated through the chloroplastic PEP-CK and the remaining (about 30%) OAA through the mitochondrial NAD-ME. Pyruvate stimulation of aspartate decarboxylation is discussed; a pyruvate-alanine shuttle and an aspartate-alanine shuttle are proposed between the mesophyll and bundle-sheath cells during aspartate decarboxylation through the PEP-CK and NAD-ME system respectively.
Ionic environment and the contraction of isolated rat-liver mitochondria by adenosine triphosphate.

Abstract Contraction of thyroxine-swollen rat-liver mitochondria by adenosine triphosphate is essentially independent of the ionic environment, since it proceeds maximally in media containing K + , Na + , Li + , Rb + , NH 4 4 or Tris ++ as major cation or Cl − , Br − , I − , F − , NO 3 − , ClO 3 − , ClO 4 − , SO 4 = , or acetate − as major anion. Contraction also occurs over a wide range of osmolarity, as well as in distilled water with minimum possible ionic strength. The adenosine triphosphate-induced contraction also occurs in mitochondria in which the ability for oxidative phosphorylation and for specific K + -binding is completely lost by aging. These findings thus exclude the possibility that water extrusion from mitochondria by adenosine triphosphate is indirect and dependent on active ion fluxes between extra- and intramitochondrial compartments. It is therefore more probable that adenosine triphosphate produces a contractile change in the membrane leading to a decrease in volume by extrusion of water and at least some low-molecular weight solutes.
Concerted evolution and higher-order repeat structure of the 1.709 (satellite IV) family in bovids.

The 1.709 or satellite IV repeated DNA family originally isolated from the domestic cow was analyzed using Southern blotting, pulsed field gel electrophoresis, fluorescence in situ hybridization, and DNA sequencing in species belonging to the genera Bos, Bison, Bubalus, Syncerus, Boselaphus, and Tragelaphus. Hybridization indicates that the family has been amplified in Bos, Bison, Bubalus, and Syncerus but not in Boselaphus or Tragelaphus. Pericentromeric, higher-order repeat substructure exists in all species, with multimeric arrays ranging in size from 10 to 1500 kb. Sequence analysis of a 492-bp PCR product revealed comparable levels (0.2–4.5%) of intra- and interspecific divergence when species of Bos and Bison were compared, supporting the idea that species of these two genera should be recognized under the genus Bos. Alternatively, all Syncerus sequences cluster as a monophyletic group on an evolutionary tree and differ from those of Bos/Bison by about 13%. Comparing these findings with the fossil record indicates that concerted evolution has occurred since Bos/Bison and Syncerus last shared a common ancestor (5.0 MYA) but before the radiation of the genus Bos (2.5 MYA): GenBank accession numbers AY517856-AY517904.
Levetiracetam in children with refractory status epilepticus

The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.
Cocinas Públicas: Food and Border Consciousness in Greater Mexico

Food is fundamental to the workings of identity and belonging, power, and social change. This special issue of Food & Foodways addresses such critical concepts by exploring cocinas publicas of Greater Mexico. We locate this investigation of Mexican foodways within the contexts of social hierarchy, spatial division, political economy, narrative, identity, and place. Articles in this volume address some of the following questions: How do public foods and public kitchens impact our conceptualizations of gender, class, ethnicity, and age as well as regional, national, and transnational identities? How are individual and collective identities, communities, and economies shaped, contested and negotiated through public food practices? In what ways do the production and consumption of food intertwine the public kitchen with the domestic kitchen? In what ways do these spaces oppose or contradict each other? How do the production, distribution, and/or consumption of food in public spaces impact regional history, cu...
Developing the Integrated Transportation and Ecological Enhancements for Montana Process: Applying the "Eco-Logical" Approach

Construction and maintenance of transportation systems can result in direct, indirect, and cumulative effects on ecosystems. Mitigation of unavoidable adverse impact typically occurs on a project-by-project basis and commonly attempts to restore the same affected resource near the site at which the impact occurs. This piecemeal approach may fulfill regulatory requirements, but greater mitigation value may be achieved with a similar investment by evaluating and prioritizing off-site mitigation opportunities in the context of the entire ecosystem. In addition, project-by-project environmental permitting practices involve repetitious procedures that sometimes unpredictably delay project delivery. A recent federal guide encourages agencies to plan infrastructure projects and related mitigation with goals of conserving and connecting important habitat collaboratively and strategically, while increasing predictability and transparency of planning and regulatory permitting processes. This guide, Eco-Logical: An ...
pH dependence of the n.m.r. line broadening of water by paramagnetic EDTA chelates

Abstract The effect of pH and temperature upon the n.m.r. line width of solutions of the ethylenediaminetetraacetic acid (EDTA) chelates of copper(II), nickel(II) and iron(III) has been studied. The concentration of these chelates required to give a line width of 10 Hz is only a factor of about two greater than the hydrated metal ions. This result indicates rapid exchange of the solvent from a coordination site on the chelated metal ion. The temperature dependence of the n.m.r. spectra shows that in each case the line width is controlled by the relaxation time of the proton in the paramagnetic environment of the coordinated metal ion rather than the rate of solvent exchange. The pH dependence of the solvent line width is related to the formation of protonated and hydroxy complexes of the chelates as confirmed by potentiometric titration.
Effects of bifunctional interactions in the chemical ionization mass spectrometry of carboxylic acids and methyl esters

The methane chemical ionization mass spectra of dodecan-1, 10-dioic acid and the methyl ester show enhanced water and methanol elimination relative to monofunctional analogs. Elimination of acetic acid from 1,10-diacetoxydecane, however, was reduced relative to 1-acetoxydecane. This appears to be the result of bifunctional interactions. The steric requirement of this interaction is shown in an homologous series of dicarboxyl compounds. The change in interfunctional separation is shown to affect the proton and ammonium ion affinities in the ammonia chemical ionization spectra of the dicarboxyl compounds in a manner explained in terms of proton and ammonium ion complex formation. The observation is extended to various other functional groups.