cssi/SciSciGPT-SciSciNet huggingface dataset:
Hydroxamic acids in asymmetric synthesis.

Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst’s center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed.Because of their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless asymmetric epoxidation, which uses the titanium–tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydrox...
The moons of Saturn

Knowledge gained of the 17 Saturn moons with observations by the Voyager spacecraft are reviewed. Titan was found to have the only atmosphere, which is opaque and precludes geologic inferences. Synchronous rotation is experienced by the 14 inner moons, with a constant inner face turned toward the planet. Phoebe is too far away from the planet to lose its spin to planetary tidal forces, and has an orbit inclined 150 deg from the equatorial plane, while Iapetus is inclined 14.7 deg in its orbit. The abundance of ice on the moons is accepted as evidence of condensation formation of the moons at very low temperatures. Newly discovered moons of Saturn, including both the shepherd moons, which are suspected to maintain the rings in place, and the moons discovered by earth-based astronomy, are discussed. Finally, photographs of all the moons are examined for definitive details.
The effect of temperature on radiation-induced macromutants of Arachis Hypogaea L. and expression of heterosis in F1 hybrid populations

Three separate experiments were conducted with cultivated peanuts to (a) study the effect of four controlled temperatures on the expression of seven radiation-induced macromutants and the mother line; (b) determine the responses of normal appearing F 1 hybrids involving four macromutants to three controlled temperature regimes and (c) evaluate the same macromutant, parental and F 1 hybrid populations (described in b) when grown for a full season under field conditions. Macromutant plant weights and flower production were generally lower than that of the mother line in all three experiments. The macromutants also tended to flower later than the mother line. The leaflet expression of two of the macromutants was drastically influenced by changes in temperature. Lupinus reached maximum leaflet curvature when grown at 34/30°C but appeared near normal when grown at 22/18°C. The reverse was true for the macromutant Recurved. The macromutant Flop contained maximum percentages of nitrogen and phosphorus in its vegetative parts when grown at the highest temperature (34/30°C). All other mutants and the mother line had highest proportions of these nutrients when grown at the lowest temperature regime (22/18°C). Expressions of heterosis were maximized when hybrids of macromutant parentage were grown at suboptimal temperatures. General combining ability estimates were higher than specific combining ability estimates with the macromutant Hedera (a dwarf type) making the greatest contribution to the general combining ability effects for peg (fruit-bearing structure) production and pegging efficiency. The same macromutant was found to make substantial contributions to general combining ability effects for fruit and seed weight when hybrids were grown under field conditions.
Unsupervised learning for graph matching

Graph matching is an important problem in computer vision. It is used in 2D and 3D object matching and recognition. Despite its importance, there is little literature on learning the parameters that control the graph matching problem, even though learning is important for improving the matching rate, as shown by this and other work. In this paper we show for the first time how to perform parameter learning in an unsupervised fashion, that is when no correct correspondences between graphs are given during training. We show empirically that unsupervised learning is comparable in efficiency and quality with the supervised one, while avoiding the tedious manual labeling of ground truth correspondences. We also verify experimentally that this learning method can improve the performance of several state-of-the art graph matching algorithms.
The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience

Abstract Purpose Despite improvements in the management of persistent pulmonary hypertension of the newborn (PPHN), a number of infants with inadequate gas exchange are treated with extracorporeal membrane oxygenation (ECMO). The objectives of this study were to use the Extracorporeal Life Support Organization Registry to review the outcomes of neonates with PPHN receiving ECMO, and to identify pre-ECMO variables that may be associated with increased mortality. Materials and methods The study is a retrospective analysis of all patients with PPHN supported with ECMO and reported to the Extracorporeal Life Support Organization registry from 2000 to 2010. Prematurity was defined as t -test or Fisher's exact test. Variables found to be statistically significant underwent multivariate analysis by logistic regression. Kaplan-Meier survival curves were generated to analyze the relationship between duration of ECMO support and patient survival. Results A total of 1569 neonates with PPHN received ECMO support during the study period, at an average age of 3.1 d of life and for a duration of 6.9 d. Survival among neonates with PPHN receiving ECMO support was 81%, and those receiving support for 7, 10, 14, and 21 d survived at rates of 88%, 78%, 55%, and 25%, respectively. By logistic regression, prematurity ( P P = 0.02), pre-ECMO SaO 2 ≤65% ( P = 0.01), and duration of ECMO ≥7 d ( P Conclusions Neonates with PPHN have high survival rates with ECMO support. Prematurity, acidosis, and profound hypoxemia are independently associated with increased mortality. Furthermore, prolonged ECMO support (>7 d) is associated with a higher risk of mortality in this cohort than in patients supported for
Cryopreservable and tumorigenic three-dimensional tumor culture in porous poly(lactic-co-glycolic acid) microsphere.

Abstract In vitro tumor models that mimic in vivo conditions may be ideal for screening anticancer drugs and their formulations and developing tumors in animal models. Three-dimensional (3-D) culture of cancer cells on polymeric scaffolds can be an option for such models. In the present study, porous poly(lactic acid-co-glycolic acid) (PLGA) microsphere was used both as a cancer cell culture substrate to expand cells and as a cancer cell transplantation vehicle for tumor construction in mice. MCF-7 cells cultured on porous PLGA microspheres in stirred suspension bioreactors expanded by 2.8-fold over seven days and maintained viability. At three months after inoculation with 2 × 106 cells/site, the tumor formation by MCF-7 cells cultured on microspheres was much more effective (4 tumors/5 mice) than its counterpart cultured on plates (1/5). More importantly, cell viability and metabolic activity were not significantly changed even after one freeze–thaw cycle of the 3-D culture. MCF-7 cells cultured on the microspheres and the cells in 3-D after cryopreservation were more resistant to doxorubicin than MCF-7 cells cultured on plates.
Detecting Reversion in T4rII Bacteriophage to r+ induced by Ultra-Violet Irradiation

Details of a test developed for estimating the extent of reversion of bacteriophage T4B from rII to r+ induced by ultravolet irradiation are given. T4rII mutants were obtained by ultraviolet irradiation of T4Br phage, and 12 hr cultures of E. coli and K-12 ( lambda ) were used in assays of rII and r+ phage, respectively. The phage were diluted and irradiated in media which contained, per liter ion-free water, 10 g tryptone, 8 g sodium chloride, and 1 g glucose. Each of 12 rII mutant stocks was assayed on B and on K-12 ( lambda ) to determine accurately the titer of total and of r+ phage. It was found that 5 of the 12 mutants revert to r+ when irradiated with ultravolet. The extent of reversion ranges from 1.81 to 4.2 x 105 r+ per 106 survivors.
Circumventricular Organs: A Novel Site of Neural Stem Cells in the Adult Brain

Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin+, β-tubulin III+) and glial (S100β+, GFAP+, RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.
Cell specific cytotoxicity and uptake of graphene nanoribbons.

Abstract The synthesis of oxidized graphene nanoribbons (O-GNR) via longitudinal unzipping of carbon nanotubes opens avenues for their further development for a variety of biomedical applications. Evaluation of the cyto- and bio-compatibility is necessary to develop any new material for in vivo biomedical applications. In this study, we report the cytotoxicity screening of O-GNRs water-solubilized with PEG-DSPE (1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]), using six different assays, in four representative cell lines; Henrietta Lacks cells (HeLa) derived from cervical cancer tissue, National Institute of Health 3T3 mouse fibroblast cells (NIH-3T3), Sloan Kettering breast cancer cells (SKBR3) and Michigan cancer foundation-7 breast cancer cells (MCF7). These cell lines significantly differed in their response to O-GNR-PEG-DSPE formulations; assessed and evaluated using various endpoints (lactate dehydrogenase (LDH) release, cellular metabolism, lysosomal integrity and cell proliferation) for cytotoxicity. In general, all the cells showed a dose-dependent (10–400 μg/ml) and time-dependent (12–48 h) decrease in cell viability. However, the degree of cytotoxicity was significantly lower in MCF7 or SKBR3 cells compared to HeLa cells. These cells were 100% viable upto 48 h, when incubated at 10 μg/ml O-GNR-PEG-DSPE concentration, and showed decrease in cell viability above this concentration with ∼78% of cells viable at the highest concentration (400 μg/ml). In contrast, significant cell death (5–25% cell death depending on the time point, and the assay) was observed for HeLa cells even at a low concentration of 10 μg/ml. The decrease in cell viability was steep with increase in concentration with the CD 50 values ≥ 100 μg/ml depending on the assay, and time point. Transmission electron microscopy of the various cells treated with the O-GNR solutions show higher uptake of the O-GNR-PEG-DSPEs into HeLa cells compared to other cell types. Additional analysis indicates that this increased uptake is the dominant cause of the significantly higher toxicity exhibited by HeLa cells. The results suggest that water-solubilized O-GNR-PEG-DSPEs have a heterogenous cell-specific cytotoxicity, and have significantly different cytotoxicity profile compared to graphene nanoparticles prepared by the modified Hummer's method (graphene nanoparticles prepared by oxidation of graphite, and its mechanical exfoliation) or its variations.
Eberhard the German and the Labyrinth of Learning: Grammar, Poesy, Rhetoric, and Pedagogy in Laborintus

Abstract: Eberhard the German9s Laborintus , the first of the artes poetriae to be printed, has received comparatively little scholarly attention. Both Kelly and Murphy have noticed that the work conveys a pedagogical emphasis. This essay, however, demonstrates that Laborintus is not merely a manual for teachers of verse. Rather, the work is a delightful maze of verse, grammar, and rhetoric, a labyrinth of learning containing an allegorical account of grammar, poesy, and rhetoric. On one level, the rhetorical figures are used as inventional schemes for the composition of verse in proper meter. However, the examples used in Eberhard9s account of the rhetorical figures also contain Christian homilies on faith and action that are exemplary primers for teachers. The homilies in tum underscore Eberhard9s pedagogical theory, which is ultimately the key to his labyrinth.
The influence of alumina passivation on nano-Al/Teflon reactions

Abstract The reaction kinetics of aluminum (Al) and polytetrafluoroethylene (PTFE or Teflon) were recently examined using nanoparticles of both Al and Teflon. Results showed a unique pre-ignition reaction (PIR) associated with the nano-Al/Teflon mixture that was not significant in the micron-Al/Teflon mixture. The PIR is caused by fluorination of the alumina (Al2O3) shell passivating the Al particles and reduces the onset temperature of Al ignition for nano compared with micron particle mixtures. Because the alumina shell was found to play a key role in the reaction mechanism, this communication extends our understanding of the interaction between alumina and Teflon by examining the influence of alumina particle size, and therefore surface area, on the fluorination reaction with Teflon. Differential scanning calorimetry analysis show that reaction kinetics vary dramatically as the alumina particle size is reduced from 50 to 15 nm diameter. Specifically, for 15 nm diameter alumina, the first exotherm (corresponding to the PIR) exhibits three times more heat of reaction than for the 30, 40, or 50 nm alumina particles. These results show how particle size and specific surface area affect the Al–Teflon reaction mechanism.
Characterization of Dislocations in (112)B HgCdTe/CdTe/Si

The electrical performance of HgCdTe/Si photodiodes is shown not to have a direct relationship with the dislocation density as revealed by defect etching. This has led to an equivalent circuit model to explain the relationship of the dislocation density and the electrical test data. A new (112)B HgCdTe/CdTe/Si and CdTe/Si etch pit density (EPD) etch has been demonstrated. The new etch has been used to look for distinctive features which may be responsible for the poor electrical performance of individual diode pixels. The new etch chemistry also reduces the surface roughness of the etched epilayer and makes EPD determination less problematic. The new (to HgCdTe) technique of electrostatic force microscopy has also been used to analyze the electrical properties of dislocations.
SU-GG-T-373: The Effect of Vessel Material on Fricke Dosimeter Yield

Purpose: To investigate the effect of solid water vessel in contact with the fricke dosimeter yield in terms of surface to volume ratio and storage time. Material and methods: Fricke solution was made up with the highest pure commercial available chemicals. The optical density was measured using the Varian Cary 400 UV‐Vis spectrophotometer provided with a temperature controller. Three set of ten cylindrical containers (internal radius of 0.5 cm and height 3.5 cm) were made of solid water, polystyrene, and PMMA. Containers have been filled with fricke solution of 4.3, 4.5, and 5 cm−1surface to volume ration, and sealed with Mylar material. Optical density readings at 304 nm were performed in 120 minutes time interval, 30 minute step. The effects of solid water material on the Fricke dosimeter yield (surface to volume ratio and storage time) were compared against those values obtained for polystyrene and PMMA materials. Results: The deviation of the optical density for a surface to volume ratio ranging from 4.3 to 5 cm−1 was 0.01%, 0.01%, and 0.02% for PMMA, Polystyrene, and solid water, respectively. The maximum deviation among the different materials in the same surface to volume ratio range did not exceed 0.04%. Within the uncertainty of measurement (0.06%) no effect of solid water, polystyrene, and PMMA containers was observed on the Fricke dosimeter yield during the storage time interval of 120 minutes. Conclusion: Solid water plastic can be used to store Fricke solution and can still be comparable to polystyrene and PMMA. It has the advantage to have physical properties very close to water. Keywords:Surface to volume ratio, PMMA, Fricke dosimeter yield, solid water
Pathologic Aspects of Inflammatory Breast Carcinoma: Part 1. Histomorphology and Differential Diagnosis

Inflammatory breast carcinoma (IBC) is rare, but it is the most aggressive variant of breast cancer. Because a diagnosis of IBC is usually based on the presence of typical clinical symptoms that are not always associated with certain pathologic characteristics, the diagnosis often presents a great challenge even to the most experienced clinicians. Even more, IBC has not been associated with a specific histologic tumor type. With recent epidemiologic and molecular evidence now suggesting that IBC is a distinct disease entity rather than a subtype of locally advanced breast cancer, the accurate differentiation of this disease has never been more crucial to ensuring appropriate treatment. The focus of this chapter is on the histomorphologic characteristics of IBC and its broad differential diagnosis.
Nepotism vs Tit-For-Tat, or, why should you be nice to your rotten brother?

It is well known that interactions among relatives facilitate the evolution of altruistic behaviours. Game theoretic models show, however, that guarded altruism (such as Tit-For-Tat) can evolve among non-relatives when individuals interact many times and ‘cheating’ behaviours can be punished. Strangely, no one has yet asked whether the guarded altruism that evolves among non-relatives might also evolve among close relatives, supplanting unconditional altriusm. We present a series of one-locus sexual haploid models in which Tit-For-Tat, unconditional altruists and selfish individuals interact in groups of full siblings. Tit-For-Tat frequently (but not always) replaced unguarded altruism, in which case the strategic ‘rules’ for interacting with kin vs non-kin are identical. Even when Tit-For-Tat is selected at a single locus, however, by withholding altruism for non-reciprocating relatives it may qualify as an ‘outlaw’ from the standpoint of modifier genes at other loci.
Longitudinal Study of Occupational Therapy Students' Beliefs About Knowledge and Knowing

Research has demonstrated the importance of beliefs about knowledge and knowing, or epistemic and ontological cognition (EOC), to learning and achievement; however, little research has examined occupational therapy students' EOC or determined whether occupational therapy programs promote its development. This study examined changes in EOC over 18 mo of didactic coursework in an occupational therapy program. Thirty-one students completed the Epistemic Beliefs Inventory at the beginning, middle, and end of 18 mo of didactic coursework. Results indicated no difference in ontological cognition. However, change occurred in epistemic cognition, with students demonstrating statistically significantly weaker beliefs in justification of knowledge by an omniscient authority by the end of the didactic portion of the program. Although causal inferences cannot be made from this small study of one cohort of occupational therapy students, it is possible that intensive study in the discipline of occupational therapy contributed to change in these students' epistemic cognition.
Value and limitations of heart rate-adjusted ST segment depression criteria for the identification of anatomically severe coronary obstruction: Test performance in relation to method of rate correction, definition of extent of disease, and β-blockade

Abstract Performance of the linear regression-based ST/HR (heart rate) slope, the simple ST/HR index, and ST segment depression alone for the identification of anatomically severe coronary obstruction was examined in relation to the definition of the extent of disease and the presence or absence of β-blockade during treadmill exercise using the Cornell protocol in 172 catheterized patients. Whether severe disease was defined by three-vessel obstruction, by Gensini scores partitioned at 35 or at 48, or by Duke jeopardy scores exceeding 6, the 83% to 100% sensitivities of an ST/HR slope criterion of 6.0 μV/beat/min were each significantly higher than the corresponding 65% to 80% sensitivities of 150 μV of ST segment depression at closely matched specificities. The ST/HR slope was significantly more sensitive than a simple ST/HR index criterion of 3.4 μV/beat/min for detection of high Gensini scores, but despite consistently intermediate performance trends, in no case did sensitivity of the simple ST/HR index criterion significantly exceed that of ST depression alone. Each method performed better and with comparable sensitivity in patients not receiving β-blockers. In contrast, the 82% to 100% sensitivities of the ST/HR slope for identification of severe disease were significantly higher than the 63% to 77% sensitivities of ST depression in patients taking β-blocking drugs; however, simple heart rate adjustment using the ST/HR index had intermediate performance that in no case was significantly more sensitive than ST segment depression alone. Accordingly, the relative performance of heart rate adjusted and standard electrocardiographic criteria can be expected to vary with the method of heart rate correction of ST segment depression, with the definition of severe obstruction, and with the proportion of β-blocked patients in the study population.
Increase competition to stabilize drug prices.

Donald Kennedy's condemnation of Senator Ron Wyden's (D-OR) proposal to punish research universities by taxing successful technology transfer that leads to profitable pharmaceuticals is, for the most part, well reasoned (Editorial, “Drug prices: real problem, wrong solution,” 8 Jun., p. [1797][1
Requirements for adenosine triphosphate in DNA repair in isolated hepatic nuclei

Abstract ATP appeared to play several roles during DNA repair in isolated hepatic nuclei. It stimulated carcinogen-activated reparative DNA synthesis, it prevented degradation of newly synthesized DNA and it suppressed the accumulation of single-strand breaks in DNA. The results suggest DNA repair is an energy-dependent process using DNA polymerase, DNA-dependent ATPase and DNA ligase.
Complications and treatment failures of video-assisted thoracoscopic debridement for pediatric empyema

Purpose Video-assisted thoracoscopic debridement (VATD) is a well-established intervention to treat pediatric empyema. There is ongoing controversy at what stage in the treatment algorithm it should be utilized. To shed further light onto this debate, we reviewed our institutional experience looking for factors predicting treatment failure or complications of VATD.
Rurality, gender, and mental health treatment.

Mental health problems are common and costly, yet many individuals with these problems either do not receive care or receive care that is inadequate. Gender and place of residence contribute to disparities in the use of mental health services. The objective of this study was to identify the influence of gender and rurality on mental health services utilization by using more sensitive indices of rurality. Pooled data from 4 panels of the Medical Expenditure Panel Survey (1996–2000) yielded a sample of 32,219 respondents aged 18 through 64. Variables were stratified by residence using rural–urban continuum codes. We used logistic and linear regression to model effects of gender and rurality on treatment rates. We found that rural women are less likely to receive mental health treatment either through the general healthcare system or through specialty mental health systems when compared to women in metropolitan statistical areas (MSA) or urbanized non-MSA areas. Rural men receive less mental health treatment than do rural women and less specialty mental health treatment than do men in MSAs or least rural non-MSA areas. Reported mental health deteriorates as the level of rurality increases. There is a considerable unmet need for mental health services in most rural areas. The general health sector does not seem to contribute remarkably to mental health services for women in these areas. Key words: disparities, gender, mental health, rurality
Statistical algorithms accounting for background density in the detection of UXO target areas at DoD munitions sites

Statistically defensible methods are presented for developing geophysical detector sampling plans and analyzing data for munitions response sites where unexploded ordnance (UXO) may exist. Detection methods for identifying areas of elevated anomaly density from background density are shown. Additionally, methods are described which aid in the choice of transect pattern and spacing to assure with degree of confidence that a target area (TA) of specific size, shape, and anomaly density will be identified using the detection methods. Methods for evaluating the sensitivity of designs to variation in certain parameters are also discussed. Methods presented have been incorporated into the Visual Sample Plan (VSP) software (free at http://dqo.pnl.gov/vsp) and demonstrated at multiple sites in the United States. Application examples from actual transect designs and surveys from the previous two years are demonstrated.
Economic constraints in hypertext

Hypertext organization is being touted as the appropriate data organization for effective CD-ROM information retrieval. But the producer of a hypertext database incurs significant costs in providing these benefits because of the expense of constructing indices and linkages. This research investigates the cost of constructing a hypertext database and provides a straightforward approach to forecasting costs of creating and maintaining a hypertext database. Cost forescasting can determine whether organizations can internally fund a hypertext database; it can also determine whether producers can afford to bring hypertext databases or technology to market
Dynamic phase imaging and processing of moving biological organisms

This paper describes recent advances in developing a new, novel interference Linnik microscope system and presents images and data of live biological samples. The specially designed optical system enables instantaneous 4-dimensional video measurements of dynamic motions within and among live cells without the need for contrast agents. "Label-free" measurements of biological objects in reflection using harmless light levels are possible without the need for scanning and vibration isolation. This instrument utilizes a pixelated phase mask enabling simultaneous measurement of multiple interference patterns taking advantage of the polarization properties of light enabling phase image movies in real time at video rates to track dynamic motions and volumetric changes. Optical thickness data are derived from phase images after processing to remove the background surface shape to quantify changes in cell position and volume. Data from a number of different pond organisms will be presented, as will measurements of human breast cancer cells with the addition of various agents that break down the cells. These data highlight examples of the image processing involved and the monitoring of different biological processes.
Behavior-based multi-robot collaboration for autonomous construction tasks

The robot construction crew (RCC) is a heterogeneous multi-robot system for autonomous construction of a structure through assembly of long components. The two-robot team demonstrates component placement into an existing structure in a realistic environment. The task requires component acquisition, cooperative transport, and cooperative precision manipulation. A behavior-based architecture provides adaptability. The RCC approach minimizes computation, power, communication, and sensing for applicability to space-related construction efforts, but the techniques are applicable to terrestrial construction tasks.
Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

The adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract are well described. Evidence also shows that NSAIDs can be harmful to the small intestine. The use of NSAIDs has been associated with small intestinal strictures, ulcerations, perforations, diarrhea, and villous atrophy. Herein we present a case of NSAID-induced enteropathy with multiple diaphragmlike strictures that involved the distal 3S em of ileum and review the literature of other cases of NSAID-induced enteropathy in which biopsy specimens were obtained for histologic analysis to rule out other causes. The prevalence of NSAID-induced enteropathy is unknown. Diagnosis can be made by endoscopy or at abdominal exploration. The role of radionuclide scans for diagnosis remains unclear. The pathogenesis is likely multifactorial. Mucosal diaphragms may be specific for NSAID-related disease. Treatment options for NSAID-induced enteropathy are discussed.
Regulations guiding the interstate shipment of investigational product.

Purpose:Investigational drug services (IDSs) are often responsible for delivery of investigational product, whether to a study participant pursuant to a prescription or in bulk to another investiga...
An alternative analysis of apparent EKC-type transitions

Abstract The hypothesis of the environmental Kuznets curve (EKC) depends upon the assumption that countries pass through a similar environmental impact trajectory as they experience income growth, implying that income levels determine pollution levels. The authors present evidence that this is not representative of the way many individual country’s pollution emission trajectories evolve and question the emphasis on ‘income determinism’ by the EKC. The study proposes that nonlinear dynamic systems analysis provides a more complete description of individual country pollution trajectories. In the case of CO 2 emissions, the nonlinear time trajectories show abrupt transitions that occur contemporaneously with historical events and over a broad range of incomes.
Spatial economic networks with multicriteria producers and consumers: Statics and dynamics

In this paper, we develop a framework for the formulation, analysis, and computation of solutions to spatial network problems in which the firms are multicriteria decision-makers and the consumers are as well. In particular, the firms, which are involved in the production of a homogeneous commodity, are spatially separated and weight the two criteria of profit maximization and total output maximization in distinct fashion. They are faced with the selection of modes/routes (which are modeled in an aggregated manner) to transport the commodity to the demand markets where consumers, consisting of different classes, consider the price charged by the producers and weight the transportation cost and the transportation time of the product on the links in an individual manner. We derive the governing equilibrium conditions and present the variational inequality formulation. We provide qualitative properties of the equilibrium commodity shipment and generalized price pattern and then propose a tatonnement process, which we formulate as a projected dynamical system. We give an algorithm for computational purposes and apply it to several numerical examples for illustration purposes. This paper is the first to integrate multicriteria decision-making on the production side and on the consumption side in a basic network context.
Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells.

Alterations in DNA methylation are important in cancer, but the acquisition of these alterations is poorly understood. Using an unbiased global screen for CpG island methylation events, we have identified a non-random pattern of DNA hypermethylation acquired in p16-repressed cells. Interestingly, this pattern included loci located upstream of a number of homeobox genes. Upon removal of p16INK4A activity in primary human mammary epithelial cells, polycomb repressors, EZH2 and SUZ12, are up-regulated and recruited to HOXA9, a locus expressed during normal breast development and epigenetically silenced in breast cancer. We demonstrate that at this targeted locus, the up-regulation of polycomb repressors is accompanied by the recruitment of DNA methyltransferases and the hypermethylation of DNA, an endpoint, which we show to be dependent on SUZ12 expression. These results demonstrate a causal role of p16INK4A disruption in modulating DNA hypermethylation, and identify a dynamic and active process whereby epigenetic modulation of gene expression is activated as an early event in breast tumor progression.
Editing of Glutamate Receptor Subunit B Pre-mRNA by Splice-site Variants of Interferon-inducible Double-stranded RNA-specific Adenosine Deaminase ADAR1

The interferon-inducible RNA-specific adenosine deaminase (ADAR1) is an RNA-editing enzyme that catalyzes the deamination of adenosine in double-stranded RNA structures. Three alternative splice-site variants of ADAR1 (ADAR1-a, -b, and -c) occur that possess functionally distinct double-stranded RNA-binding motifs as measured with synthetic double-stranded RNA substrates. The pre-mRNA transcript encoding the B subunit of glutamate receptor (GluR-B) has two functionally important editing sites (Q/R and R/G sites) that undergo selective A-to-I conversions. We have examined the ability of the three ADAR1 splice-site variants to catalyze the editing of GluR-B pre-mRNA at the Q/R and R/G sites as well as an intron hotspot (+60) of unknown function. Measurement of GluR-B pre-mRNA editing in vitro revealed different site-specific deamination catalyzed by the three ADAR1 variants. The ADAR1-a, -b, and -c splice variants all efficiently edited the R/G site and the intron +60 hotspot but exhibited little editing activity at the Q/R site. ADAR1-b and -c showed higher editing activity than ADAR1-a for the R/G site, whereas the intron +60 site was edited with comparable efficiency by all three ADAR1 splice variants. Mutational analysis revealed that the functional importance of each of the three RNA-binding motifs of ADAR1 varied with the specific target editing site in GluR-B RNA. Quantitative reverse transcription-polymerase chain reaction analyses of GluR-B RNA from dissected regions of rat brain showed significant expression and editing at the R/G site in all brain regions examined except the choroid plexus. The relative levels of the alternatively spliced flip and flop isoforms of GluR-B RNA varied among the choroid plexus, cortex, hippocampus, olfactory bulb, and striatum, but in all regions of rat brain the editing of the flip isoform was greater than that of the flop isoform.
The thermal polymerization of amino acids. The role and fate of the reactants.

Amino acid containing polymers were synthesized by heating mixtures of aspartic acid, glutamic acid, glycine, alanine, valine, leucine, isoleucine, and proline in the absence of water at temperatures of 180° to 190°C for several hours. The resulting product was fractionated by dialysis, gel filtration, and chromatography and electrophoresis on paper. The larger polymers were found to be rich in aspartic acid and poor in proline, while the smaller molecules were rich in glutamic acid and contained proline as a significant constituent. The N-terminal positions are believed to be occupied largely by pyroglutamic acid, while the C-terminal positions are comprised exclusively of aliphatic amino acids. Aspartic acid and glutamic acid were individually treated to the polymerization conditions. Little reaction of aspartic acid was observed, but glutamic acid formed a melt and upon cooling a glass. Investigation of this product indicated it to be a highly hydrogen bonded system of pyroglutamic and glutamic acids. The model system of glutamic acid and decylamine produced under polymerization conditions, the decylamide of pyroglutamic acid. The accumulated results suggest a model for thermal polymerization.
Asbestos-Penicillin Induced Pleurodesis: An Experimental Study

SUMMARY In the experimental animal, a gritty paste containing asbestos powder and penicillin crystals measuring up to 1,000 micra in length (Pen-A-Brasive), effectively destroys the mesothelial lining and leads to a firm obliteration of the pleural cavity. Utilizing a thoracoscope for introduction, the method finesses a thoracotomy and has led to minimal complications. The method has a limited potential in man for the production of pleural symphysis.
HDAC6 and Microtubules Are Required for Autophagic Degradation of Aggregated Huntingtin

CNS neurons are endowed with the ability to recover from cytotoxic insults associated with the accumulation of proteinaceous polyglutamine aggregates via a process that appears to involve capture and degradation of aggregates by autophagy. The ubiquitin-proteasome system protects cells against proteotoxicity by degrading soluble monomeric misfolded aggregation-prone proteins but is ineffective against, and impaired by, non-native protein oligomers. Here we show that autophagy is induced in response to impaired ubiquitin proteasome system activity. We show that ATG proteins, molecular determinants of autophagic vacuole formation, and lysosomes are recruited to pericentriolar cytoplasmic inclusion bodies by a process requiring an intact microtubule cytoskeleton and the cytoplasmic deacetylase HDAC6. These data suggest that HDAC6-dependent retrograde transport on microtubules is used by cells to increase the efficiency and selectivity of autophagic degradation.
Correction of ventricular septal defect in childhood.

Abstract One hundred and two consecutive patients underwent operative repair of ventricular septal defect with 9 operative deaths. Preoperative cardiac catheterization was performed in 100 patients. Severe pulmonary hypertension was present preoperatively in 8 of the 9 patients who died. Two patients had permanent heart block. Postoperative cardiac catheterization was performed in three-quarters of the surviving patients. Two patients had significant residual ventricular septal defect. The 92 surviving patients have been followed up to eleven years postoperatively and are asymptomatic.
Counting Quality, Not Hours: Understanding the Impact of Duty Hour Reform on Internal Medicine Residency Education

One year ago, the Accreditation Council for Graduate Medical Education (ACGME) imposed new resident duty hour regulations that particularly affect the most junior postgraduate learners.1 These requirements focus on enhanced supervision and oversight, and limit postgraduate year (PGY-1) residents to 16 hours of continuous duty. We expect data to emerge soon regarding the impact of the second round of duty hour reform on patient care outcomes. However, two articles in this issue of JGIM focus on the urgent need for medical educators to measure the nature and quality of resident learning and patient care activities in the context of reduced resident duty hours.
Teaching Economics Using Historical Novels: Jonathan Harr's The Lost Painting

Undergraduate students are often interested in and benefit greatly from applications of economic principles. Historical novels drawn from real-world situations can engage students with economic concepts in new ways and provide a useful tool to help enhance instruction. In this article, the authors discuss the use of historical novels generally in microeconomics, and examine The Lost Painting, a historical novel by Jonathan Harr (2005), in detail. Topics illustrated in the novel include scarcity, opportunity cost, cost-benefit analysis, tax avoidance, labor market specialization, compensating wage differentials, competition and market structure, pricing, income, and government regulation. The authors include an in-depth description of how to incorporate a historical novel into a microeconomics class and provide some evaluation strategies.
Effects of Channel Size and Shear Rate on Platelet Margination

When an arterial wall is injured, white clots form rapidly to prevent blood loss. In addition to hemostasis, under pathophysiological conditions, white clots can occlude atherosclerotic arteries. Such occlusive clots can cause ischemic cardiac arrest in less than an hour[1, 2]. Determining the predominant rate limiting processes governing thrombosis growth rate can guide us in identifying patients at increased risk of atherothrombosis.Copyright © 2013 by ASME
Fiber Optic Spectroelectrochemical Sensing for In-Situ Determination of Metal Ions

Abstract In situ chemical sensing techniques are increasingly used for a variety of applications, including industrial process control, on‐site environmental assessment, and detection of explosives and chemical and biological weapons. A common category of sensors for such purposes entails the use of optical fibers for making spectral measurements of target compounds or species derived from these compounds via physical, chemical, enzymatic, or immunologic reactions. A less common but potentially advantageous approach involves the electrochemical conversion of the analyte subsequent to its spectroscopic detection. These spectroelectrochemical schemes represent versatile, essentially reagent‐free analyses that could provide superior alternatives to existing methods. Reported here is a summary of progress made by the authors' group toward the development of fiber optic spectroelectrochemical sensors for in situ measurements. The aqueous copper (II)/copper (0) couple was chosen as a model system to investigate...
More Kronoseismology with Saturn's rings

In a previous paper (Hedman and Nicholson 2013), we developed tools that allowed us to confirm that several of the waves in Saturn's rings were likely generated by resonances with fundamental sectoral normal modes inside Saturn itself. Here we use these same tools to examine eight additional waves that are probably generated by structures inside the planet. One of these waves appears to be generated by a resonance with a fundamental sectoral normal mode with azimuthal harmonic number m=10. If this attribution is correct, then the m=10 mode must have a larger amplitude than the modes with m=5-9, since the latter do not appear to generate strong waves. We also identify five waves with pattern speeds between 807 degrees/day and 834 degrees/day. Since these pattern speeds are close to the planet's rotation rate, they probably are due to persistent gravitational anomalies within the planet. These waves are all found in regions of enhanced optical depth known as plateaux, but surprisingly the surface mass densities they yield are comparable to the surface mass densities of the background C ring. Finally, one wave appears to be a one-armed spiral pattern whose rotation rate suggests it is generated by a resonance with a structure inside Saturn, but the nature of this perturbing structure remains unclear. Strangely, the resonant radius for this wave seems to be drifting inwards at an average rate of 0.8 km/year over the last thirty years, implying that the relevant planetary oscillation frequency has been steadily increasing.
Removal of swine zonae pellucidae with sequential exposures to pronase and acidified medium.

Abstract Exposure to acidified PBS (pH 3) for 60 sec removed swine zonae pellucidae from 70.4% of 27 swine morulae, and 73.7% of these formed blastocysts in culture. Further investigations revealed that treating embryos with 0.5% pronase and acidified PBS (pH 3) for 30 sec each was more effective. Zonae were removed in 90.6% of 85 embryos (four-cell to morulae) treated. A total of 76.9% of 65 zona-free embryos and 81.6% of 38 untreated embryos formed blastocysts (P > 0.05). An additional 57 untreated and 49 zona-free embryos (morulae to blastocysts) were transferred to seven recipient sows. Four sows returned to estrus (18 to 27 days), but three others were pregnant when slaughtered at 38 to 42 days. One pregnant sow had received a combination of five zona-free and six untreated embryos and demonstrated the potential for further development of treated embryos in vivo.
Long-Term Effects of Inducible Mutagenic DNA Repair on Relative Fitness and Phenotypic Diversification in Pseudomonas cichorii 302959

Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for ∼500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of “round” and “fuzzy” colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.
Calculation of the Potential of Mean Force for the Binding of Glucose to Benzene in Aqueous Solution

Molecular dynamics simulations employing umbrella sampling techniques have been used to calculate the potential of mean force (pmf) for the binding of a β-d-glucopyranose molecule to a benzene molecule in aqueous solution, as a model for the binding of sugar substrates to phenylalanine residues in proteins. The interaction of these two molecules was found to be strongly affected by hydration, as expected, with their nonpolar faces pairing by hydrophobic association to minimize the exposure of apolar groups to water. The pmf for the approach of these molecules is oscillatory in character, with two primary low-energy minima separated by a high free energy barrier, and with the net binding energy being approximately 1.1 kcal/mol and the intervening barrier being almost 2 kcal/mol. A third, weaker minimum was observed between 11 and 12 A. The oscillatory nature of the pmf results from the successive removal of water layers between the two molecules as they approach one another.
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.

Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting that it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process.