cssi/SciSciGPT-SciSciNet huggingface dataset:
Predicting response to short-acting bronchodilator medication using Bayesian networks

Aims: Bronchodilator response tests measure the effect of β2-agonists, the most commonly used short-acting reliever drugs for asthma. We sought to relate candidate gene SNP data with bronchodilator response and measure the predictive accuracy of a model constructed with genetic variants. Materials & methods: Bayesian networks, multivariate models that are able to account for simultaneous associations and interactions among variables, were used to create a predictive model of bronchodilator response using candidate gene SNP data from 308 Childhood Asthma Management Program Caucasian subjects. Results: The model found that 15 SNPs in 15 genes predict bronchodilator response with fair accuracy, as established by a fivefold cross-validation area under the receiver-operating characteristic curve of 0.75 (standard error: 0.03). Conclusion: Bayesian networks are an attractive approach to analyze large-scale pharmacogenetic SNP data because of their ability to automatically learn complex models that can be used f...
A longitudinal study of cerebral blood flow over the first 30 months.

To investigate prospectively the development of cerebral perfusion during infancy, serial quantitative measurements of cerebral blood flow (CBF) volume were performed in two healthy children from birth up to the age of 30 mo. A total of 28 CBF volume measurements were done in either of the children. Absolute flows were measured in the internal carotid and vertebral arteries on both sides. Blood flow was calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. Starting from 67 and 80 mL/min, respectively, at birth an almost 10-fold increase of CBF volume was observed in both children during the examination period. Half of this rise occurred during the first 6 mo, probably reflecting the steep metabolic incline during this period of synaptogenesis. The continuous increase in CBF volume after the sixth month of life mainly corresponds to brain growth. Estimated CBF (based on estimated brain weights) increased from 21 and 23 mL 100 g−1 min−1, respectively, after birth to 46 and 53 mL 100 g−1 min−1, respectively, during the first 6 mo of life in both children, remaining stable thereafter. This study is the first to provide longitudinal data of CBF during the first 30 mo after birth.
The interactive roles of zinc and calcium in mitochondrial dysfunction and neurodegeneration

Zinc has been implicated in neurodegeneration following ischemia. In analogy with calcium, zinc has been proposed to induce toxicity via mitochondrial dysfunction, but the relative role of each cation in mitochondrial damage remains unclear. Here, we report that under conditions mimicking ischemia in hippocampal neurons - normal (2 mM) calcium plus elevated (> 100 μM) exogenous zinc - mitochondrial dysfunction evoked by glutamate, kainate or direct depolarization is, despite significant zinc uptake, primarily governed by calcium. Thus, robust mitochondrial ion accumulation, swelling, depolarization, and reactive oxygen species generation were only observed after toxic stimulation in calcium-containing media. This contrasts with the lack of any mitochondrial response in zinc-containing but calcium-free medium, even though zinc uptake and toxicity were strong under these conditions. Indeed, abnormally high, ionophore-induced zinc uptake was necessary to elicit any mitochondrial depolarization. In calcium- and zinc-containing media, depolarization-induced zinc uptake facilitated cell death and enhanced accumulation of mitochondrial calcium, which localized to characteristic matrix precipitates. Some of these contained detectable amounts of zinc. Together these data indicate that zinc uptake is generally insufficient to trigger mitochondrial dysfunction, so that mechanism(s) of zinc toxicity must be different from that of calcium.
The Passage to Adulthood: Challenges of Late Adolescence.

Late adolescence and the period following, often referred to as emerging adulthood, have been noted as particularly important for setting the stage for continued development through the life span as individuals begin to make choices and engage in a variety of activities that are influential for the rest of their lives. Demographic, sociocultural, and labor market changes have made the years between ages eighteen and twenty-five more transitional than in the recent past. This chapter reviews the critical assets and needs that are essential for keeping youth on healthy, productive pathways into adulthood and examines the developmental tasks and changes of late adolescence.
Capillary electrophoresis as a tool for the analysis of protein folding

Abstract The utility of capillary electrophoresis (CE) was demonstrated for the analysis of a model protein, bovine trypsinogen, as it underwent oxidation from a fully reduced molecule through a distribution of intermediate species until the disulfide bond conformation corresponding to that of the globular native structure was reached. Through the use of CE, completely refolded (native) trypsinogen was resolved from both the reduced protein and intermediate refolded conformations. In addition, the presence of polyethylene glycol in the separation buffer was determined to provide size-based protein separations of significantly higher resolution than those obtained in phosphate buffer alone. Quantitation of native trypsinogen in refolded material revealed an excellent correlation between CE determinations and analyses by established techniques such as biological activity assay and high-performance size-exclusion and cation-exchange chromatography. These results, together with a comparative consistency of CE separations with those obtained via non-denaturing slab gel electrophoresis and isoelectric focusing, suggest that CE can be an effective technique useful for the analysis of protein refolding.
Light-emitting diodes based on InP quantum dots in GaP(100)

The growth, fabrication, and device characterization of the light-emitting diodes based on InP quantum-dot within a GaP matrix and on a GaP(100) substrate are described and discussed. The diode structures are grown using gas-source molecular beam epitaxy. Electroluminescence has been measured under a variety of bias conditions and temperatures. A green emission line at about 550 nm appears to result from carrier recombination in the strained InP wetting layer. Carrier recombination in the InP quantum dots results in red emission at about 720 nm.
Knowledge development in nursing: our historical roots and future opportunities.

Abstract The historical development of American nursing research in the past century is traced, and projections for nursing in the 21st century are offered.
Collective accelerator for electrons.

A concept for collective acceleration and focusing of a high-energy electron bunch is presented. The scheme combines an intense relativistic electron beam propagating in low-density gas with a trailing picosecond laser pulse for prompt photoionization of the gas to create the intense collective fields.
Effects of chronic social separation on cardiovascular disease risk factors in female cynomolgus monkeys

A lack of social support is associated with increased risk of coronary heart disease morbidity and mortality in human beings. Similarly, chronic social separation (single cage housing) potentiates atherosclerosis in female monkeys. Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate this effect (as both are associated with increased atherosclerosis), heart rate and luteal phase plasma progesterone concentrations were measured in 12 female cynomolgus monkeys that were first socially housed, then individually housed, and finally returned to their original social groups. Afternoon heart rates increased during social separation compared to the social groupings (P<0.001). Increased heart rates could not be explained by activity levels, which were lower during social separation than in social groupings (P<0.001). Ovarian function (i.e. luteal-phase progesterone concentrations) was not influenced by housing condition. Single caging reduced the extent of social signaling, even though animals were in visual and auditory contact. Rates of affiliative behaviors increased and time spent alone decreased in post-reunion social groups compared to pre-separation social groups (P's<0.01). The results indicate that chronic social separation in this group-living species may exacerbate atherosclerosis via altered autonomic activity, as evidenced by higher heart rates during social separation.
Ionic Mechanisms that Underlie Ventricular Action Potential Prolongation following Loss of Caveolin-3 in Adult Transgenic Mice

Caveolin proteins are involved in establishing membrane microstructure, lipid raft organization, and cell signaling. In the heart, caveolin-3 (Cav3) predominates. Inherited or disease-induced Cav3 loss increases risk of sudden cardiac death (SCD). We aimed to explore connections between Cav3 loss and arrhythmogenic changes in the ventricular action potential (AP) by investigating the Cav3 dependence of ionic currents. Drugs commonly used to disrupt or remove Cav3 in cultured cells exclude any compensatory process likely to occur in vivo. This motivated us to engineer a novel conditional Cav3 knockout (Cav3-/-) mouse that survives to adulthood. We isolated ventricular cells for electrophysiological experimentation.AP duration (APD90) was prolonged from 24±4 ms in WT to 96±9 ms in Cav3-/-, and several currents were affected. Reduced peak: L-type Ca2+ current (ICaL), 21%; slow K+ current, 81%; transient outward K+ current, 57%; steady state outward K+ current (Iss), 43%. Late Na+ current was enhanced ∼10-fold. These changes were partially offsetting - preventing a simple account for the APD90 increase. To relate changes in currents to changes in the AP, we developed a computational representation of Cav3-/- based on the Morotti et al. mouse ventricular cell model and defined by fractional change in currents.Unexpectedly, the relatively small change in relatively small Iss caused 33% of total simulated AP prolongation. Though Iss conductance was reduced, peak Iss actually increased in the dynamic setting of the simulated AP. Early in the AP, lower Iss indirectly enhanced inward currents (importantly late ICaL) by extending the plateau phase, which in turn allowed Iss to more fully activate. This Iss/ICaL process largely accounted for the pro-arrhythmic APD90 increase following Cav3 loss and is therefore a candidate target for normalizing SCD risk.
Drop out from primary to secondary school in Mexico: A life course perspective

Abstract Preventing school dropout is a critical feature of the Millennium Development Goals. Yet, as primary school enrollments become universal, dropout rates in Mexico near 50% by the end of formal schooling. Using a unique, nationally representative data set (Mexico Family Life Survey) we track children ages 5–11 in 2002 to the years 2005–2006 to determine how many have students have dropped out of school. We then apply a life-course perspective to determine if the influences of family, school and macro-factors interact with the child's level of schooling and the transition from primary to secondary school. We find that the transition to secondary school has the highest dropout rates. Rurality matters most during this transition. As family factors are the most predictive indicator of dropout, the family's influence is dynamic over time—the role of mother's education fades while the influence of an unemployed father grows.
Evidence for single top quark production at D0

We present evidence for the production of single top quarks at the Fermilab Tevatron p collider. Using a 0.9 fb-1 dataset collected with D0 detector, the analysis is performed in the electron+jets and muon+jets decay modes, taking special care in modeling the large backgrounds, applying a new powerful b-quark tagging algorithm and using three multivariate techniques to extract the small signal. The combined measured production cross section is σ(p tb + X, tqb + X) = 4.7 ± 1.3 pb. The probability to measure a cross section at this value or higher in the absence of signal is 0.014%, corresponding to a 3.6 standard deviation significance. We use the cross section measurement to directly determine the CKM matrix element that describes the Wtb coupling and find 0.68 < |Vtb|≤ 1 at 95% C.L. within the standard model.
Did Pocahontas Save Captain John Smith

By the mid-19th century, Captain John Smith, the early Colonial expolorer and settler, was a well-known figure in American history. The story of how, in 1607, the Powhatan princess Pocahontas saved from execution by her tribe appeared in all the standard American histories. Numerous plays, novels and poems were devoted to the episode. Starting in the 1860s, however, scholars began to question Smith's published accounts of the Pocahontas incident, and a controversy ensued, with Henry Adams becoming Smith's most famous detractor. Today many scholars continue to regard Smith as a vainglorious braggart who lied about his rescue. "Did Pocahontas Save Captain John Smith?" is an analysis of the historiography of this debate. Examining the primary and secondary evidence J.A. Leo Lemay aims to demonstrate that the incident did in fact occur. As Lemay notes, Adams' case against Smith (first published in 1867) hinged primarily on the fact that Smith's earliest accounts of his experiences in Virginia made no references to Pocahontas' intervention. It was not until 1624 that Smith published the well-known account of his rescue by Pocahontas. Following Adams and others who attacked Smith, a Hungarian scholar asserted in 1890 that Smith had also bragged and lied about his experiences in eastern Europe during the Hungarian wars against the Turks. This claim added fuel to the general scepticism about Smith's veracity as an historical reporter. Scholarly findings in the 20th century rehabilitated Smith's reputation somewhat by showing that the descriptions of the places and battles he had witnessed during his European adventures were accurate. Still, many felt that no convincing evidence existed to prove the Pocahontas story. A valuable rebuttal to Adams had been published by William Wirt Henry in 1875, but it was largely ignored and forgotten. As he re-evaluates the evidence, Lemay deduces that many old Virginia hands could have learned the story only from the Powhatan Indians. Moreover, even Smith's enemies - who were in a position to refute his story - never expressed doubt that Pocahontas had saved the Captain. The Reverend Samuel Purchas, who interviewed the Virginia colonists and the Indians who visited England, believed and repeated Smith's description of the incident. Finally, according to Lemay, Henry Adams' original attack on Smith was actually written during the Civil War as a South-baiting polemic and suppresses pertinent evidence. A tightly argued study, "Did Pocahontas Save Captain John Smith?" not only refutes the outright sceptics, it reverses the prevailing judgement that the truth will never be known.
Does asphyxia cause cerebral palsy

The incidence of cerebral palsy is 1 per 1,000, whereas the proportion caused by perinatal asphyxia is only 8% to 10%. The purpose of this article is to review the relationship between asphyxia and cerebral palsy. Only a minority of cases, those involving severe pathological fetal academia, are consistently associated with neonatal encephalopathy and an increased risk of cerebral palsy.
SCFs in the new millennium

Substrate-specific degradation is a key feature of the ubiquitin proteasome system. Substrate specificity is typically directed by the E3 or ubiquitin ligase; such specificity can be conferred either by ligase modification or expression or conversely via modification of substrates that permit their recognition by a specific E3 ligase. The most well-known example of such complexes are the Cullin-RING ligases (CRLs). CRLs are composed of one of seven cullin-family scaffold proteins; the CRL serves as a scaffold that interacts directly with a RING-domain enzyme (Rbx1/2) through an extensive protein-protein interface within the globular C-terminal domain. At the N terminus, the cullin associates with an adaptor protein through cullin-repeat motifs. This adaptor, in turn, facilitates recruitment of a substrate-specifying factor that recruits the target to be ubiquitylated. The prototypical CRL is the cul1-containing complex, commonly referred to as the Skp1-Cul1-Fbox (SCF) ligase. SCF ligases contribute to the timely destruction of numerous substrates thereby ensuring normal cell growth. The importance of SCF function is highlighted by cancer-specific alterations in either the expression or the function of select F-box substrate-specific adaptors that results in neoplastic conversion. Herein, we discuss the current understanding of SCF function and contribution to cell biology.
The X-ray structure of the hydroxycarbene complex [(DPPP)(CO)3MnC(OH)CH3]+[CF3SO3]− {facial-[1,3-bis(diphenylphosphino)propane(methyl-hydroxycarbene) tricarbonylmanganese(I)]} triflate

Abstract The cationic octahedral manganese(I) hydroxycarbene complex [(DPPP)(CO) 3 MnC(OH)CH 3 ] + ] has been synthesized and isolated as its triflate salt, and its structure fully determined by X-ray diffraction. A comparison of our cationic Mn 1 methylhydroxycarbene complex to the neutral isoelectronic Cr 0 and Mo 0 phenylhydroxycarbene structures reported in the literature reveals a number of surprising differences and similarities. In the Cr and Mo complexes the metal fragment and the hydroxy hydrogen are positioned syn ( Z -isomer) giving the conformational isomer often seen in alkoxycarbenes. In contrast, in our Mn complex, these substituents are found in the alternate anti conformation ( E -isomer). In addition, dimers are observed in the solid state due to a much more intricate network of hydrogen bonds. Nevertheless, in each of these octahedral isoelectronic hydroxycarbene complexes, the orientation of the memtal framework and the carbene moiety with respect to each other is remarkably similar. A twist of approximately 34° about the MC(carbene) bond and away from the fully eclipsed electronically favored geometry is observed in all three complexes.
Newcastle Disease Immunization Studies 4. Vaccination of Chickens with B1, F and Lasota Strains of Newcastle Disease Virus Administered through the Drinking Water

ABSTRACT PREVIOUS studies have demonstrated the efficacy of immunizing chickens against Newcastle disease (ND) with B1 strain Newcastle disease virus (NDV) administered through the drinking water under laboratory and field conditions (Winterfield and Seadale, 1955Winterfield and Seadale, 1956Winterfield and Seadale, 1957a,b). In this investigation, F and LaSota NDV strains were used as vaccines in addition to the B1. The results are presented in this paper. MATERIALS AND METHODS B1 strain NDV (Hitchner and Johnson, 1948) vaccine was prepared from stock virus maintained in the authors’ laboratory. F strain NDV was obtained in a dry state from the Newcastle Disease Repository, University of Wisconsin, and the LaSota strain was isolated from a commercial vaccine. The F and LaSota strains were passed through three generations in embryonated chicken eggs before being used as vaccines. Each vaccine was in the form of amnioallantoic fluid (AAF) obtained from infected embryos. The same vaccine pool of each strain was used . . .
Molecular Dynamics Simulations of DPPC Bilayers Using “LIME”, a New Coarse-Grained Model

A new intermediate resolution model for phospholipids, LIME, designed for use with discontinuous molecular dynamics (DMD) simulations is presented. The implicit-solvent model was developed using a multiscale modeling approach in which the geometric and energetic parameters are obtained by collecting data from atomistic simulations of a system composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules and explicit water. In the model, 14 coarse-grained sites that are classified as 1 of 6 types represent DPPC. DMD simulations performed on a random solution of DPPC resulted in the formation of a defect-free bilayer in less than 4 h. The bilayer formed quantitatively reproduces the main structural properties (e.g., area per lipid, bilayer thickness, bond order parameters) that are observed experimentally. In addition, the bilayer transitions from a liquid-crystalline phase to a tilted gel phase when the temperature is reduced. Transbilayer movement of a lipid from the bottom leaflet to the top l...
A Low-Cost, Systematic Methodology for Soft Error Robustness of Logic Circuits

Due to current technology scaling trends such as shrinking feature sizes and decreasing supply voltages, circuit reliability is becoming more susceptible to radiation-induced transient faults (soft errors). Soft errors, which have been a great concern in memories, are now a main factor in reliability degradation of logic circuits as well. In this paper, we present a systematic and integrated methodology for circuit robustness to soft errors. The proposed soft error rate (SER) reduction framework, based on redundancy addition and removal (RAR), aims at eliminating those gates with large contribution to the overall SER. Several metrics and constraints are introduced to guide the RAR-based approach toward SER reduction. Furthermore, we integrate a resizing strategy into our framework, as post-RAR additive SER optimization. The strategy can identify most critical gates to be upsized and thereby, minimize area and power overheads while maintaining a high level of soft error robustness. Experimental results show that the proposed RAR-based framework can achieve up to 70% reduction in output failure probability. On average, about 23% SER reduction is obtained with less than 4% area overhead.
History: Holistic browsing

D. Graham Burnett muses on an exhibition exploring the legacy of Stewart Brand's eco-handbook.
Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

The transcription factor nuclear factor-kappaB (NF-κB) plays a central role in stress-induced transcriptional activation and has been implicated in chemoresistance of cancers. In the present study, we investigated the role of NF-κB in inducible chemoresistance of neuroblastoma. Doxorubicin, VP16 and the cytotoxic ligand TRAIL trigger NF-κB activation, whereas cisplatin and taxol have no impact on NF-κB activity. Specific inhibition of NF-κB activation by overexpression of dominant-negative mutant IκBα-super-repressor does not alter cell death upon doxorubicin or VP16 treatment, although it prevents doxorubicin- or VP16-mediated NF-κB activation. By comparison, inhibition of TRAIL-stimulated NF-κB activation by IκBα-superrepressor or the small molecule NF-κB inhibitor BMS-345541 significantly enhances TRAIL-induced apoptosis, pointing to an antiapoptotic function of NF-κB in TRAIL-mediated apoptosis. Analysis of signaling pathways reveals that NF-κB inhibition prevents TRAIL-triggered up-regulation of Mcl-1, promoting TRAIL-induced cytochrome c release and activation of caspases. Accordingly, knockdown of Mcl-1 by RNA interference significantly enhances TRAIL-induced apoptosis and also increases sensitivity of neuroblastoma cells to CD95- or chemotherapy-induced apoptosis. In conclusion, NF-κB regulates apoptosis in a stimulus-specific manner in neuroblastoma cells and confers protection against TRAIL-induced apoptosis. By demonstrating that NF-κB inhibition sensitizes neuroblastoma cells for TRAIL-induced apoptosis, our findings have important implications. Thus, NF-κB inhibitors may open new perspectives to potentiate the efficacy of TRAIL-based protocols in the treatment of neuroblastoma. © 2008 Wiley-Liss, Inc.
Quasi-Bayesian Analysis Using Imprecise Probability Assessments And The Generalized Bayes’ Rule

The generalized Bayes’ rule (GBR) can be used to conduct ‘quasi-Bayesian’ analyses when prior beliefs are represented by imprecise probability models. We describe a procedure for deriving coherent imprecise probability models when the event space consists of a finite set of mutually exclusive and exhaustive events. The procedure is based on Walley’s theory of upper and lower prevision and employs simple linear programming models. We then describe how these models can be updated using Cozman’s linear programming formulation of the GBR. Examples are provided to demonstrate how the GBR can be applied in practice. These examples also illustrate the effects of prior imprecision and prior-data conflict on the precision of the posterior probability distribution.
Evaluation of Effectiveness of Stop Sign Treatments at Highway-Railroad Grade Crossings

The safety benefit of stop sign treatments at passive highway-rail crossings has been a subject of research for many years. The objective of this study is to assess the effectiveness of the stop sign treatment on crossing safety. Using the FRA database, the research focused on 26 years of vehicle-train accident history in the United States from 1980 through 2005. A before-and-after and cross-sectional statistical analysis was conducted for 7,394 public highway-railroad grade crossings that were upgraded from being controlled only by crossbucks to stop signs, without other traffic control devices or automatic countermeasures. The study found that accident rates based on annual accident frequency per 1,000 crossings were significantly higher during the period when crossings were controlled only by crossbucks than when they were controlled by stop signs. Further, this study developed negative binomial accident prediction models for paved and unpaved highway-rail grade crossings that included the effect of st...
Gravimetric Calibration of Critical Flow Venturi Nozzles

The Metering Research Facility (MRF) was commissioned in 1995/1996 at Southwest Research Institute for research on, and calibration of natural gas flow meters. A key commissioning activity was the calibration of critical flow Venturi (sonic) nozzles by a gravimetric proving process flowing nitrogen or natural gas at different pressures. This paper concerns the calibration of the four sonic nozzles installed in the MRF Low Pressure Loop (LPL). Recently, a new project prompted a review of the relations used to calculate sonic nozzle discharge coefficient in the LPL data acquisition computer code. New calibrations of the LPL sonic nozzles were performed flowing natural gas over a lower range of pressure than used in the original commissioning tests. The combination of new and old gravimetric calibration data are shown to agree well with correlations published by Arnberg and Ishibashi (2001) and by Ishibashi and Takamoto (2001) for laminar, transitional and turbulent boundary layer flow in critical flow Venturi nozzles.Copyright © 2004 by ASME
Multiscaling behavior in transition economies

Abstract A comparable statistical analysis for the currency exchange rates of the countries with transition economies has been made. Self-criticality has been demonstrated and studied. Non-linear effect for self-criticality indexes has been demonstrated. All effects are essentially nonlinear and differ from ones in the advanced economies.
The self-association in aqueous solutions of morphine sulphate and some related salts.

Conductivity and optical rotatory dispersion investigations suggest that morphine sulphate and some related salts aggregate in aqueous solution. This association is probably due to the stacking of the aromatic rings.
Heterogeneity of Colorectal Cancer (CRC) in reference to KRAS proto-oncogene utilizing WAVE technology

Abstract Background New drugs targeting specific genes required for unregulated growth and metastases have improved survival rates for patients with metastatic colorectal cancer. Resistance to monoclonal antibodies specific for the epidermal growth factor receptor (EGFR) has been attributed to the presence of activating point mutations in the proto-oncogene KRAS. The use of EGFR inhibitor monotherapy in patients that have KRAS wild type has produced response rates of only 10–20%. The molecular basis for clinical resistance remains poorly understood. We propose two possible explanations to explain these low response rates; 1) levels of resistant CRC cells carrying mutated KRAS are below the sensitivity of standard direct sequencing modalities ( Methods In a collaborative effort with the surgical and molecular pathology departments, 3 formalin fixed paraffin embedded tissue blocks of human CRC were obtained from the human tissue bank maintained by the Lifespan Pathology Department and/or the human tissue bank maintained by the Molecular Pathology Core of the COBRE for Cancer Research Development. The three specimens previously demonstrated KRAS mutations detected by the Applied Biosystems Kit. The Wave system 4500 (high performance ion-pairing liquid chromatography (IP-HPLC)) was utilized to evaluate tissue for the presence of KRAS proto-oncogene mutations at codons 12 and 13. Results Initially, the sensitivity of WAVE technology was compared with direct sequencing by evaluating a dilutional series. WAVE detected mutant alleles at levels of 2.5% compared to 20% performed with standard direct sequencing. Samples from three patients were evaluated by WAVE technology. Eight samples from patient 1 were analyzed. In two of eight samples, no mutations were detected at concentrations as low as 5%. In one sample a mutation was noted by WAVE and not by direct sequencing. All four samples from patient 2 tested positive for Exon 12/13 mutations. Of the seven samples from patient 3, five were positive for Exon 12/13 mutations and two were negative for Exon 12/13 mutations. Conclusion In these studies the analysis of three patients' colorectal cancer tissues were analyzed utilizing the WAVE technology. Results demonstrated a greater degree of sensitivity in mutation detection when compared to standard sequencing. These studies also demonstrated heterogeneity of expression of KRAS mutations between areas of the tissue samples at a genomic level. The low clinical response rates to EGFR inhibition might be explained by the variation in mutation presence, which was dependent upon the region examined. The heterogeneity demonstrated in these studies provides another phenotypic variant that will impact clinical care.
A genetic analysis of linkage group I of Chlamydomonas reinhardi.

Crossing over in linkage group I ofChlamydomonas reinhardi was studied by means of the analysis of 1721 unordered tetrads. The data indicate that chiasma interference is positive, that chromatid interference is absent and that crossing over occurs at the 4-strand stage.
Host-seeking behavior of selected Chrysops species (Diptera: Tabanidae) harboring trypanosomatidae (Kinetoplastida)

The host-seeking behavior of hematophagous arthropods can be altered by symbiotes, thereby biasing sampling techniques and inaccurately reflecting symbiote or vector prevalence. Knowledge of any altered vector behavior is essential in vector control and monitoring. Species of Chrysops are vectors of human and animal pathogens. Six species of Chrysops were collected at two locations in South Carolina to determine if diurnal host-seeking behavior was influenced by trypanosomatid infection. Fifty-five percent of the host-seeking Chrysops were infected with trypanosomatid parasites. Prevalence of infection in host-seeking Chrysops were statistically indistinguishable during both the morning and evening at both sites. The results indicate that the prevalence of parasites among wild host-seeking Chrysops might not be influenced by infection status.
Applying active space principles to active classrooms

Recent developments in pervasive computing have enabled new features for collaboration and instrumentation in educational technology systems. An infrastructure for the integration of components which support interactive pervasive education aids the development of these features. The e-Fuzion system contains the necessary components and management facilities to dynamically compose an adaptive learning system. e-Fuzion provides a set of distributed objects which allow for sharing of multimedia, recording of learning activity, and availability of real-time feedback information for instructors. Using the Gaia infrastructure, the system supports context-aware components and storage. e-Fuzion provides the extensibility necessary for the development of features to be integrated into educational technology systems.
Integrated risk analysis of global climate change

Abstract This paper discusses several factors that should be considered in integrated risk analyses of global climate change. We begin by describing how the problem of global climate change can be subdivided into largely independent parts that can be linked together in an analytically tractable fashion. Uncertainty plays a central role in integrated risk analyses of global climate change. Accordingly, we consider various aspects of uncertainty as they relate to the climate change problem. We also consider the impacts of these uncertainties on various risk management issues, such as sequential decision strategies, value of information, and problems of interregional and intergenerational equity.
Mechanisms of Antimicrobial Resistance in Bacteria

The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (eg, β-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to ≥1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories—one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus , and a third detailing multidrug resistance in Pseudomonas aeruginosa —are reviewed to illustrate the varied ways in which resistant bacteria develop.
Children’s ideas about animal adaptations: An action research project

In this paper, I describe the action research I conducted in my third-grade science classrooms over the course of two years. In order to gain an understanding of my third-grade students’ ideas about animal adaptations and how the teaching of a unit on crayfish influenced these ideas, I used clinical interviews, observations, and written assessments. I did this research while working as a science resource teacher in a suburban elementary school. The first year, I piloted the unit myself and then made changes to the unit based upon my findings. During the second year, the entire third-grade team taught the unit, and I co-taught with one of these third-grade classroom teachers. I found that students’ ideas are developing and that connections to other parts of the science curriculum such as habitats, gases, and plants were necessary yet lacking. Teachers should be prepared to understand these connections themselves and to highlight them to students. Also, as other research indicates, a complex understanding of adaptations is difficult and perhaps not developmentally appropriate for elementary students. Teachers should recognize that elementary students will not develop an understanding of adaptations from merely working with and observing animals in their habitats. Further research is needed to see if the students need specific lessons on adaptations, an understanding of evolution, and/or more experience and maturity in order to truly understand the concept of adaptation.
Altered chemokine response in an animal model of multiple organ dysfunction syndrome induced by zymosan.

Abstract Purpose The aim of this study was to determine the monocyte chemoattractant protein-1 (MCP-1) response over time in an animal model of multiple organ dysfunction syndrome (MODS). Methods On day 0, rats were randomized to receive an intraperitoneal injection of zymosan at a dose of 1 mg/g of body weight (n = 36) or vehicle (n = 9). Serum, peritoneal lavage (PL) fluid, and bronchoalveolar lavage (BAL) fluid were collected from 3 rats in the control group and 6 to 7 rats in the zymosan group at days 1, 5, and 12. Monocyte chemoattractant protein-1 concentrations were determined by enzyme-linked immunosorbent assay. Results The authors observed a 47% mortality in the zymosan-treated rats. Monocyte chemoattractant protein-1 levels were unchanged in the serum, PL, and BAL of control animals. Both serum and PL MCP-1 were significantly higher in zymosan-treated rats on days 1 ( P P Conclusions Chemokines are increased systemically and locally during MODS. The fact that MCP-1 is significantly higher early in the course of MODS may suggest that this chemokine is important in the early inflammatory changes that lead to MODS later in the course of this illness.
Cytokine-Induced Anorexia: Behavioral, Cellular, and Molecular Mechanismsa

Cytokines induce anorexia. Recent issues concerning mechanistic aspects are: (1) Cytokines induce anorexia through different modes of behavioral action, that is, by affecting meal size, meal duration, and meal frequency differentially. Profiles also depend on the concentration or dosage. (2) The interface between the periphery and brain. Specific cytokines may be transported from the periphery to the brain. Cytokines generate mediators that can act on peripheral and/or brain target sites. Cerebrovasculature endothelium can also generate signals to modulate neural activities. Evidence indicates that the proposed vagal afferent signaling requires reassessment. Because of paracrine and autocrine actions, local cytokine production within the brain can induce anorexia. (3) Cytokines act directly on hypothalamic neurons proposed to participate in feeding. (4) Cytokine cytokine and cytokine peptide/neurotransmitter interactions are critical; for example, cytokines interact to induce anorexia synergistically, neuropeptide Y cytokine interactions are antagonist, and cytokine neurotransmitter and cytokine leptin neuropeptide Y CRH-glucocorticoid and other endocrine interactions are important. A leptin receptor is related to gp 130, a signal transducer among interleukin (IL)-6 subfamily receptors; gp 130 and related molecules may be an interface for feeding control in health and disease. Various cytokines upregulate leptin and gp 130. An integrative approach combining computerized meal pattern analyses with cellular and molecular approaches is being used to characterize mechanisms (ligands, receptors, transducing molecules, and intracellular mediators) involved in cytokine-induced anorexia.
From early twinges to mastery: The process of adjustment in living with rheumatoid arthritis

Objective. To describe the experiences of women who have learned to live with rheumatoid arthritis (RA), and to explore how women manage this chronic illness and the demands of their everyday lives. Methods. Thirty women with a diagnosis of RA were interviewed in their homes. The women were encouraged to “tell their story of living with RA,” from the first symptom to the present, using a semistructured questionnaire. Qualitative data were analyzed using a constant comparative analytic process. Results. Learning to live with RA was characterized by periods of uncertainty, of learning about the illness, discovering strategies that allowed the women to meet the expectations of their roles as women, and the establishment of new patterns of daily life. The women became experts at managing their RA and developed a sense of mastery in coping with their symptoms. Conclusions. Persons with RA need support and guidance, beginning with the onset of the disease, to facilitate achieving mastery in living with this chronic illness.
Parenteral nutrition associated cholestasis.

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [1-3]. With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [4-8]. A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[9-13]. However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1,14-17]. Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [18-21]. In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22]. Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5,22].
KNOWING A RULE

What is it to know how to reason correctly? After Lewis Carroll’s “What the Tortoise said to Achilles,” the more common response to this question is that knowing how to reason correctly cannot be the same as knowing a proposition, on pain of a regress. According to many, the moral of the regress is exactly that one must not confuse rules and principles. Inferential rules are supposed to differ from logical principles in at least two respects:
Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon emission computed tomography imaging study.

Background. The purpose of this study was to investigate the cerebral blood flow changes associated with the analgesic effect of acupuncture in patients with chronic pain. Methods. Seven patients presenting with a chronic pain syndrome and 5 healthy controls were included. All single-photon emission com puted tomography (SPECT) scans were acquired with a uniform protocol. The patient group was injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while experienc ing their usual level of pain. A baseline scan was acquired approximately 20 minutes after administration of the HMPAO. The patient then underwent acupuncture therapy with needles placed in points specifically selected to relieve pain. When the pain improved, as determined by a 10-digit score for pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes later for the acupuncture scan. The refer ence group also had a baseline and acupuncture scan, although the acupuncture itself was performed using a stan dardized set of needle points. Results. The reference group par ticipants were found to have significant increases in the thalamic and prefrontal cortex activity on the acupuncture scan compared to the baseline. The baseline scans of the pain patients showed significant asymmetric uptake in the thalami compared to controls. This asymmetry reversed or normalized after the acupuncture therapy. Significant correlations were observed between the change of activity in the prefrontal cortex and ipsilateral sensorimotor area. Conclusion. The results from these cases show that HMPAO-SPECT is capable of detecting changes in cerebral blood flow associated with pain and that acupuncture analgesia is associated with changes in the activity of the frontal lobes, brain stem, and thalami.
A Type IV Secretion System Contributes to Intracellular Survival and Replication of Burkholderia cenocepacia

Burkholderia cenocepacia is an important respiratory pathogen in persons with cystic fibrosis (CF). Recent studies indicate that B. cenocepacia survives within macrophages and airway epithelial cells in vitro by evading endosome-lysosome fusion. We investigated the role of a plasmid-encoded type IV secretion system in the intracellular survival, replication, and processing of B. cenocepacia. Both a wild-type strain (K56-2) and its type IV secretion system mutant (designated LC101) entered and replicated in CF airway epithelial cells and monocyte-derived macrophages. However, significantly more intracellular K56-2 than LC101 bacteria were found in both cell types at 24 h postinfection. Colocalization of bacteria with markers of the classical endocytic pathway indicated that although both K56-2 and LC101 reside transiently in early endosomes, a greater proportion of the mutant bacteria are targeted to lysosomal degradation. In contrast, wild-type bacteria escape from the classical endocytic pathway and traffic to the endoplasmic reticulum, where they replicate. Our results show that the intracellular processing of B. cenocepacia is similar in both professional and nonprofessional phagocytes and that a functional plasmid-encoded type IV secretion system contributes to the survival and replication of B. cenocepacia in eukaryotic cells.
Complete Genome Sequence of Cyanobacterial Siphovirus KBS2A

ABSTRACT We present the genome of a cyanosiphovirus (KBS2A) that infects a marine Synechococcus sp. (strain WH7803). Unique to this genome, relative to other sequenced cyanosiphoviruses, is the absence of elements associated with integration into the host chromosome, suggesting this virus may not be able to establish a lysogenic relationship.
Carbon-13 NMR chemical shifts of representative nitriles and nitro compounds

The 13C NMR chemical shifts of nitriles and nitro compounds derived from nineteen aliphatic and seven aromatic systems have been recorded and assigned. The shifts are compared with those of the hydrocarbons to give the substituent effects of the CN and NO2 groups.