cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacokinetics and bioavailabilities of hymecromone in human volunteers

Specific and ultrasensitive reverse-phase HPLC assays of the choleretic and biliary antispasmodic hymecromone (down to 0.05 ng ml-1) and its glucuronide, using fluorimetric detection, and sulfate metabolites using UV detection, were developed. Sodium salt solutions of 400 mg (over 3 min) and 800 mg (over 5 min) were infused i.v. into 6-8 normal human volunteers. The half-life of the major rate constant averaged 28 +/- 2 min (SE). Subsequently, less than 0.8 per cent of the dose was eliminated with terminal half-lives of 70-359 min. The apparent volume of distribution of hymecromone, referenced to the total plasma concentration, averaged 20.8 +/- 1.41 (Vc, central compartment volume) and 36.4 +/- 2.11 (Vss steady state volume). Hymecromone's total body clearance averaged 1413 +/- 89 ml min-1. The pharmacokinetics of hymecromone were dose-independent. Only 0.3 +/- 0.3 per cent unchanged hymecromone was renally excreted. Mostly dose-independent glucuronidated drug (93 +/- 4 per cent of the dose) was excreted in the urine; a smaller amount was renally excreted as the sulfate (1.4 +/- 0.3 per cent of the dose). The oral bioavailability estimated from the relative areas under the hymecromone plasma concentration-time curves following oral and i.v. administration of hymecromone to six volunteer subjects showed no dose-dependence and was 1.8 +/- 0.6 per cent. However, an anomalous c. 200 per cent of the glucuronide produced by i.v. hymecromone was produced from orally administered hymecromone as determined from the ratio of the AUC values of glucuronide obtained after peroral and i.v. administration of the same dose of hymecromone to demonstrate a high first-pass effect and implicate renal glucuronidation.
Discrimination in measures of knowledge monitoring accuracy.

Knowledge monitoring predicts academic outcomes in many contexts. However, measures of knowledge monitoring accuracy are often incomplete. In the current study, a measure of students’ ability to discriminate known from unknown information as a component of knowledge monitoring was considered. Undergraduate students’ knowledge monitoring accuracy was assessed and used to predict final exam scores in a specific course. It was found that gamma, a measure commonly used as the measure of knowledge monitoring accuracy, accounted for a small, but significant amount of variance in academic performance whereas the discrimination and bias indexes combined to account for a greater amount of variance in academic performance.
A Promising Indicator of Neurobehavioral Toxicity Using the Nematode Caenorhabditis Elegans and Computer Tracking

A promising screening test for neurotoxicity has been developed using a computer tracking system and a species of nematode, Caenorhabditis elegans. The animals are viewed in dark-field illumination...
fcc titanium in Ti-Al multilayers

Abstract Titanium layers 40, 90 and 220 nm thick in nickel-titanium multilayer thin films are shown to deposit with a hexagonal close packed structure that transforms to a face centered cubic structure when thinned, using an ion beam, for transmission electron microscopy. Implications for recent reports of polymorphic fcc Ti in multilayers are noted.
Acrofacial dysostosis with severe facial clefting and limb reduction

We describe two unrelated patients with a severe form of acrofacial dysostosis. Facial defects in both include coloboma of the lids, micrognathia, lateral oral clefting, palatal clefting, and severe auricular anomalies, with one showing bilateral cleft lip and right oblique facial clefting as well. Both have absent forearms and thumbs. Lower limbs were severely reduced in both infants with the feet attached either to the femur or directly to the trunk. Parental consanguinity was present in one case. The condition in these two infants appears to represent either a severe form of Nager acrofacial dysostosis or a new type of acrofacial dysostosis.
The Radio Source Cassiopeia A

THE high-resolution observations of the radio source Cassiopeia A by Ryle, Elsmore and Neville1 show for the first time details of the structure of the source that suggest an interpretation of a feature of the nebulosity connected with the source the significance of which was not clear. The nebulosity is essentially a circular shell with an outer radius of 2.0 min of arc, but it shows a flare in position angle 70° that extends to a distance of about 3.8 min of arc from the centre2. The long streaks of nebulosity plotted by Ryle et al. at the east side of the source (α = 23h 21m 21s; δ = + 58° 33.5′ and α = 23h 21m 31s; δ = + 58° 33.1′) are the brightest features of the flare. They and the fainter details of the flare extend radially while the features of the shell show no strongly preferential direction.
Modification of the response of rats to lethal levels of ozone by enzyme-inducing agents.

Abstract Rats injected daily with 30 mg/kg p -aminobenzoic acid (PABA) and exposed on day 4 to 8 ppm of the oxidant air pollutant ozone have a mean survival of 395 min, while the mean survival of uninjected control rats is 210 min and that of rats receiving a single injection of 30 mg/kg PABA just prior to ozone exposure is 212 min. These findings suggest that the mechanism by which PABA protects against ozone-induced lethal pulmonary edema is through the induction of an enzyme system. Studies with known modifiers of microsomal mixed function oxidase systems revealed that phenobarbital resulted in a decrease in rat survival time while allylisopropylacetamide resulted in an increase in survival. The phenothiazine compound chlorpromazine also resulted in an increase mean survival time after exposure to ozone.
Influence of Gamma Irradiation on Leaching of Simulated Nuclear Waste Glass: Temperature and Dose Rate Dependence in Deaerated Water

Elemental leaching rates from a simulated nuclear waste glass undergoing gamma irradiation in deaerated deionized water were evaluated as a function of temperature and gamma dose rate. Deaeration of the water eliminated nitric acid formation via air radiolysis, previously shown to substantially accelerate waste glass corrosion, and thus allowed the effects of water radiolysis alone to be measured. Water radiolysis resulted in enhanced reaction-layer thicknesses on glass samples as well as an approximate factor of three increase in the leach rate at 50°C. At 90°C, leach rates were indistinguishable for irradiated and unirradiated glasses. Most of the increase in glass dissolution occurred up to a gamma dose rate of ∼1 × 105 rad/h. Above this value, only minor further increases were observed. It is concluded that the observed glass corrosion enhancement was due to reaction with short-lived transient species generated by water radiolysis and that the effect is unlikely to significantly contribute to long-term waste isolation.
Evaluation of DNA flow cytometry as a screening test for bladder cancer

At this present time, we feel that there is no role for DNA flow cytometry (FCM), or indeed DNA studies by any other method, to be used as a screening procedure for patients with no prior history of bladder cancer due to the high false-positive rate found when monitoring exfoliated urothelial cells. On the other hand, for patients who have had a superficial transitional cell carcinoma (TCC), which has a documented 50% recurrence rate, and depending on pathological features, a progression rate from 7 to 45%, DNA FCM provides a sensitive method to predict future disease recurrence. It provides an extremely effective way to predict future progression and further acts as a method to monitor changes in the malignant potential of the patient's disease. For those patients with a past history of superficial TCC who develop abnormal ploidy without any overt tumor, 80% will, within the next four years, suffer a disease recurrence. For the patient who has a Ta TCC and receives intravesical Bacillus Calmette-Guerin (BCG), the development of abnormal ploidy in bladder washing specimens is the single best indicator for future disease recurrence. Similarly, a negative DNA FCM of a bladder washing at six months after intravesical therapy is an excellent predictor of no further occurrence. In patients with superficial TCC, ploidy of the initial and recurrent tumor predicts for future progression. Half of those patients with stage Ta bladder cancer with two successive aneuploid bladder tumors develop muscle invasive disease within one year, while three-fourths develop advanced disease within two years after recurrence of their second aneuploid lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
A sterically switched ionophore

Abstract A cyclohexane pro-ionophore is held in one chair form (non-ionophoric) by a large, tertiary, ketal moeity. Upon hydrolysis the acetyl group is small enough to be axial and the cyclohexane ring can flip to an ionophoric conformation.
MicroRNA GENE EXPRESSION SIGNATURES IN THE DEVELOPING NEURAL TUBE

BACKGROUND: Neurulation requires precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) are key modulators of cell and tissue differentiation. To define potential roles of miRNAs in development of the murine neural tube (NT), miRNA microarray analysis was conducted to establish expression profiles, and identify miRNA target genes and functional gene networks. METHODS: The miRNA expression profiles in murine embryonic NTs derived from gestational days 8.5, 9.0, and 9.5 were defined and compared utilizing miRXplore microarrays from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. Gene expression changes were verified by TaqMan quantitative Real-Time PCR. The clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined via Ingenuity Pathway Analysis. RESULTS: The miRXplore chips enabled examination of 609 murine miRNAs. Expression of approximately 12% of these was detected in murine embryonic NTs. Clustering analysis revealed several developmentally regulated expression clusters among these expressed genes. Target analysis of differentially expressed miRNAs enabled identification of numerous target genes associated with cellular processes essential for normal NT development. Utilization of Ingenuity Pathway Analysis revealed interactive biologic networks which connected differentially expressed miRNAs with their target genes, and highlighted functional relationships. CONCLUSIONS: The present study defined unique gene expression signatures of a range of miRNAs in the developing NT during the critical period of NT morphogenesis. Analysis of miRNA target genes and gene interaction pathways revealed that specific miRNAs might direct expression of numerous genes encoding proteins, which have been shown to be indispensable for normal neurulation. This study is the first to identify miRNA expression profiles and their potential regulatory networks in the developing mammalian NT. Birth Defects Research (Part A) 91:744–762, 2011. 2011 Wiley-Liss, Inc.
Maximum quasilikelihood estimation for a simplified NEAR(1) model

As alternatives to maximum likelihood estimation, conditional least squares (CLS) and maximum quasilikelihood estimation, with asymptotic properties, are investigated using a simplified NEAR(1) model. The maximum quasilikelihood estimator seems to perform better than the CLS estimator in simulations.
Early isolation from conspecific song does not affect the normal developmental decline of N-methyl-D-aspartate receptor binding in an avian song nucleus.

Early effects of experience on synaptic reorganization and behavior often involve activation of N-methyl-D-aspartate (NMDA) receptors. We have begun to explore the role of this glutamate-receptor subtype in the development of learned birdsong. Song learning in zebra finches occurs during a restricted period that coincides with extensive synaptic reorganization within neural regions controlling song behavior. In one brain region necessary for song learning, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), NMDA receptor binding is twice as high at the onset of song learning as in adulthood. In the present study, we used quantitative autoradiography with the noncompetitive NMDA antagonist [3H]MK-801 to examine more closely the developmental decline in NMDA receptor binding within lMAN and found that it occurred gradually over the period of song learning and was not associated with a particular stage of the learning process. In addition, early isolation from conspecific song did not affect [3H]MK-801 binding in lMAN at 30, 60, or 80 days. Since behavioral studies confirmed that our isolate rearing conditions extended the sensitive period for song learning, we conclude that the normal developmental decline in overall NMDA receptor binding within lMAN does not terminate the capacity for song learning. Finally, early deafening, which prevents both stages of song learning, also did not affect [3H]MK-801 binding in lMAN at 80 days, indicating that the decline in NMDA receptor binding occurs in the absence of auditory experiences associated with song development. © 1995 John Wiley & Sons, Inc.
Examining Sequences of Adolescent Substance Use Initiation Involving Over-the-Counter (OTC) Drug Abuse

Over-the-counter (OTC) drug abuse among adolescents is an increasingly visible and meaningful trend in the United States, but little research has been done to contextualize OTC drug abuse. This study examined a large sample of 152,678 middle school and high school adolescents in an attempt to understand sequences of OTC drug abuse initiation, and the sociodemographic and risk factor-related precursors thereof. We found that while many adolescents who had ever abused an OTC drug and used one or more “gateway” drugs (alcohol, cigarettes, or marijuana) initiated the use of the gateway drug first, there was also a subset of adolescents whose sequence of initiation began with OTC drug abuse. We also found that different risk factors and sociodemographic characteristics predicted different sequences of use. For example, interaction with antisocial peers predicted initiating gateway drug use prior to OTC drug abuse, but not the reverse sequence. Other predictor variables, including gender, grade, and parental at...
Mechanisms of photochemically produced turbidity in lens protein solutions

Calf alpha- and gamma-crystallin were photolyzed in 1-2 mg ml-1 aqueous solutions, using both laser and conventional UV radiation in the 297-320 nm wavelength region. Gamma-crystallin solutions became highly turbid upon UV irradiation, while alpha-crystallin developed no turbidity when irradiated under identical conditions. The photolyzed solutions were analyzed by SDS-PAGE. These gels revealed loss of normal 20 kDa polypeptide, and formation of higher molecular weight peptides, in both alpha- and gamma-crystallin, presumably as a result of photocross-linking reactions and/or protein insolubilization. Thus, although both crystallins underwent photocross-linking, significant turbidity production only occurred in gamma-crystallin. Some possible explanations for these differences are proposed, with one possibility being that most photocross-links in alpha-crystallin occur between subunits of the 1000-kDa oligomer, while in gamma-crystallin the cross-links occur between 20-kDa monomer units. Hence, cross-linking in alpha-crystallin does not affect the average size of particles in solution (or the turbidity), while cross-linking in gamma-crystallin results in a significant increase in average particle size with concomitant increase in turbidity. Another possible explanation is that UV-irradiated gamma-crystallin becomes insoluble (due to charge changes resulting in non-covalent aggregation) while alpha-crystallin does not. Other differences in the photochemical behavior of alpha- vs. gamma-crystallin were noted--gamma-crystallin photolysis rate was about 50% greater than alpha-crystallin. Alpha-crystallin photolysis yielded strong NFK-like fluorescence, while gamma-crystallin did not. One similarity was that photolyzed alpha- and gamma-crystallin lost amino acids His and Trp at about the same rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemistry of marine ligands and siderophores.

Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper. A number of important trace metal ions are complexed by organic ligands in seawater, including iron, cobalt, nickel, copper, zinc, and cadmium, thus defining the speciation of these metal ions in the ocean. In the case of iron, siderophores have been identified and structurally characterized. Siderophores are low molecular weight iron-binding ligands produced by marine bacteria. Although progress has been made toward the identity of in situ iron-binding ligands, few compounds have been identified that coordinate the other trace metals. Deciphering the chemical structures and production stimuli of naturally produced organic ligands and the organisms they come from is fundamental to understanding metal speciation and bioavailability. The current evidence for marine ligands, with an emphasis on siderophores, and discussion of the importance and implications of metal-binding ligands in controlling metal speciation and cycling within the world’s oceans are presented.
Numerical analysis of wave generation and propagation in a focused surface acoustic wave device for potential microfluidics applications

We develop a 3-D finite element model of a focused surface acoustic wave (F-SAW) device based on LiNbO/sub 3/to analyze the wave generation and propagation characteristics for devices operating at MHz frequencies with varying applied input voltages. We compare the F-SAW device to a conventional SAW device with similar substrate dimensions and transducer finger periodicity. SAW devices with concentrically shaped focused interdigital transducer fingers (F-IDTs) are found to excite waves with high intensity and high beam-width compression ratio, confined to a small localized area. F-SAW devices are more sensitive to amplitude variations at regions close to the focal point than conventional SAW devices having uniform IDT configuration. We compute F-SAW induced streaming forces and velocity fields by applying a successive approximation technique to the Navier-Stokes equation (Nyborg's theory). The maximum streaming force obtained at the focal point varies as the square of the applied input voltage. Computed streaming velocities at the focal point in F-SAW devices are at least an order of magnitude higher than those in conventional SAW devices. Simulated frequency response indicates higher insertion losses in F-SAW devices than in conventional devices, reflecting their greater utility as actuators than as sensors. Our simulation findings suggest that F-SAW devices can be utilized effectively for actuation in microfluidic applications involving diffusion limited transport processes.
Summary Proceedings From the Bronchopulmonary Dysplasia Group

Despite improvements in neonatal care, bronchopulmonary dysplasia (BPD) continues to occur in approximately one third of newborns who have birth weights of <1000 g and contributes to significant morbidity in this population. Gaps in knowledge about the prevention and treatment of BPD remain, resulting in unintended short- and long-term sequelae. In addition to chronic lung disease, preterm newborns with BPD are more likely to develop language delay, cerebral palsy, and cognitive impairments compared with preterm newborns without BPD. The pulmonary group identified 3 critical needs to enhance the design of clinical trials in neonates with BPD: (1) identify the stages of BPD; (2) define BPD more clearly; and (3) identify subtypes of BPD patients. The group determined that trials are needed for 3 areas of BPD: (1) prevention of BPD; (2) treatment of evolving BPD; and (3) treatment of established BPD. The severity of BPD is defined as mild, moderate, and severe, and subgroups among those with BPD are described. Here we identify gaps in basic science and pharmacologic knowledge that hamper investigators' ability to conduct effective BPD clinical trials and provide a list of drugs to be studied in BPD trials. Priorities for drug-class evaluation by stage of BPD are given. The pulmonary group proposes a BPD clinical-trials framework that varies according to the different stages of BPD and describes characteristics of the overall design for BPD clinical trials. Finally, we discuss trial-design issues that are common to all neonatal studies.
Heading for disaster: Fusarium graminearum on cereal crops.

SUMMARY The rapid global re-emergence of Fusarium head blight disease of wheat and barley in the last decade along with contamination of grains with mycotoxins attributable to the disease have spurred basic research on the fungal causal agent. As a result, Fusarium graminearum quickly has become one of the most intensively studied fungal plant pathogens. This review briefly summarizes current knowledge on the pathogenicity, population genetics, evolution and genomics of Fusarium graminearum. Taxonomy: Based on the sexual state Gibberella zeae (Schwein.) Petch: Superkingdom Eukaryota; Kingdom Fungi; Phylum Ascomycota; Subphylum Pezizomycotina; Class Sordariomycetidae; Subclass Hypocreomycetidae; Order Hypocreales; Family Nectriaceae; Genus Gibberella. Host range: The pathogen is capable of causing head blight or ‘scab’ on wheat (Triticum), barley (Hordeum), rice (Oryza), oats (Avena) and Gibberella stalk and ear rot disease on maize (Zea). The fungus also may infect other plant species without causing disease symptoms. Other host genera cited for Gibberella zeae or F. graminearum sensu lato (see below) are Agropyron, Agrostis, Bromus, Calamagrostis, Cenchrus, Cortaderia, Cucumis, Echinochloa, Glycine, Hierochloe, Lolium, Lycopersicon, Medicago, Phleum, Poa, Schizachyrium, Secale, Setaria, Sorghum, Spartina and Trifolium. Disease symptoms and signs: For wheat, brown, dark purple to black necrotic lesions form on the exterior surface of the florets and glume (Fig. 1). Although these lesion symptoms sometimes are referred to as scab, they are not formally related to the hyperplasia and hypertrophic epidermal growth associated with other scab diseases such as apple scab. Peduncles immediately below the inflorescence may become discoloured brown/purple. With time, tissue of the inflorescence often becomes blighted, appearing bleached and tan, while the grain within atrophies. Awns often become deformed, twisted and curved downward. In barley, infections are not always readily apparent in the field. Infected spikelets may show a browning or water-soaked appearance. Infected barley kernels show a tan to dark brown discolouration that can be similar to that caused by other kernel blighting organisms. During prolonged wet periods, pink to salmon-orange spore masses of the fungus are often seen on infected spikelets, glumes and kernels in both wheat and barley. For maize ear rot, infection occurs by way of colonizing silk and thus symptoms first appear at the ear apex. White mycelium, turning pink to red with time, colonizes kernels and may progress basipetally, covering the entire ear. Figure 1. Field-grown wheat inflorescence showing symptoms of Fusarium head blight. The third spikelet from the bottom shows a darkened necrotic lesion (‘scab’) whereas the second and fifth spikelets demonstrate tissue bleaching (‘blight’) symptoms. Photograph courtesy of Jacki Morrison, USDA ARS Cereal Disease Laboratory. Useful websites: http://www.broad.mit.edu/annotation/fungi/fusarium/mips.gsf.de/genre/proj/fusarium/ http://www.cdl.umn.edu/scab/gz-consort.html http://www.scabusa.org/
Detecting Structural Climate Change: An Air Mass-Based Approach in the North Central United States, 1958–1992

Abstract Empirical climate change studies are more beneficial when they go beyond simply reporting fluctuations in average temperature. Ideally, dynamic causes of the change should also be addressed. This strategy allows conceptual models of the associated physical-change mechanisms to be developed. The analysis of air masses can play a central role in this approach. Changes in their distribution and characteristics point to modifications in the mid-latitude general circulation. The integrated method air-mass classification scheme was applied to this problem in the north central United States (NCUS) over the 1958–1992 period. Monthly averages for relative frequency, 850-hPa temperature, and 850-hPa dewpoint temperature were calculated for every air mass in each season. There were major changes over the study period during spring and summer and minor changes in the other two seasons. In winter, northern stations showed a slight warming of continental (equivalent to continental polar) air. During spring, tr...
Preparing Teachers of Pupils with Mental Retardation: Changes in Course Offerings from 1970 to 1990

The purpose of this study was to compare and corttrast from 1970 to 1990 the typical course of study for students preparing to be teachers of pupils with mental retardation. Twenty institutions of higher education were selected for examination. An analysis of program and course descraptions from the catalogs of these institutions indicated, among other findings, the following changes from 1970 to 1990: (a) little change in the high percentage of programs offering a separate course on the characteristics of mental retardation; (b) an increase in the percentage of programs offering cross-categorical courses, options to study multiple areas of disability, and coursework on severe disabilities; and (c) a decrease in the percentage of programs that require joint preparation in special and general education. A brief review of past issues in special education teacher preparation and trends for the future are presented.
Interaction of oral bacteria with gingival epithelial cell multilayers.

Primary gingival epithelial cells were cultured in multilayers as a model for the study of interactions with oral bacteria associated with health and periodontal disease. Multilayers maintained at an air-liquid interface in low calcium medium displayed differentiation and cytokeratin properties characteristic of junctional epithelium. Multilayers were infected with fluorescently labeled Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum or Streptococcus gordonii, and bacterial association was determined by confocal microscopy and quantitative image analysis. P. gingivalis invaded intracellularly and spread cell to cell. A. actinomycetemcomitans and F. nucleatum remained extracellular and showed intercellular movement through the multilayer. S. gordonii remained extracellular and predominantly associated with the superficial cell layer. None of the bacterial species disrupted barrier function as measured by transepithelial electrical resistance. P. gingivalis did not elicit secretion of proinflammatory cytokines. However, A. actinomycetemcomitans and S. gordonii induced IL-1β, TNF-α, IL-6 and IL-8 secretion; and F. nucleatum stimulated production of IL-1β and TNF-α. A. actinomycetemcomitans, F. nucleatum and S. gordonii, but not P. gingivalis, increased levels of apoptosis after 24 h infection. The results indicate that the organisms with pathogenic potential were able to traverse the epithelium, while the commensal bacteria did not. In addition, distinct host responses characterized the interaction between the junctional epithelium and oral bacteria.
Cost-utility analysis: the nirvana to health economists and an enigma to decision-makers?

‘TTO, while not as pure scientifically as SG, allows more flexibility in how the trade-off question is posed. My experience suggests that until the risk aversion part of the SG is tempered, TTO may still be a preferable methodology due to patient understanding and acceptance.’
Measuring Substitution in Monetary-Asset Demand Systems

The Allen elasticity of substitution (AES) is widely used to study monetary-asset substitution and structural demand stability. Blackorby and Russell showed that the AES is uninformative and that the Morishima elasticity of substitution (MES) is the appropriate measure, a point overlooked in the monetary literature. Use of improper measures can lead to incorrect inferences. This article considers five alternative measures of substitution—the AES, the MES, the Hicksian and Marshallian elasticities of demand, and Mundlak's unencountered, but appealing, constant-cost elasticity of substitution. Selection of the substitution measure appropriate to respective research questions is addressed.
Implementing community-based systems of services for children and youths with special health care needs: how well are we doing?

Objective. To provide a baseline measure of the proportion of US children who meet the Maternal and Child Health Bureau's core outcomes for children with special health care needs (CSHCN). Those core outcomes include the following: 1) families of CSHCN will partner in decision making and will be satisfied with the services that they receive; 2) CSHCN will receive coordinated, ongoing comprehensive care within a medical home; 3) families of CSHCN will have adequate private and/or public insurance to pay for the services that they need; 4) children will be screened early and continuously for special health care needs; 5) community-based service systems will be organized so that families can use them easily; and 6) youths with special health care needs will receive the services necessary to make transitions to adult life, including adult health care, work, and independence. Methods. A national household survey was conducted using telephone interviews. We analyzed data on 38 866 CSHCN included in the 2001 National Survey of CSHCN and 13 579 children included in the 2001 National Health Interview Survey. We assessed the proportion of US children who met each of the 6 core outcomes for CSHCN using data from 2 surveys. Results. Success rates ranged from 6% (the core outcome on successful transition to adulthood) to 74% (the core outcome on organization of the service system). For 5 of the 6 core outcomes, success rates exceeded 50%. Conclusion. Our results indicate that, for the most part, the United States is well positioned to meet the 6 core outcomes. However, much more work lies ahead before success can be claimed. This is especially true for the core outcome on transition to adulthood, for which only 6% of children in the target population are now meeting this goal.
Activation of the Ano1 (TMEM16A) chloride channel by calcium is not mediated by calmodulin.

The Ca2+-activated Cl channel anoctamin-1 (Ano1; Tmem16A) plays a variety of physiological roles, including epithelial fluid secretion. Ano1 is activated by increases in intracellular Ca2+, but there is uncertainty whether Ca2+ binds directly to Ano1 or whether phosphorylation or additional Ca2+-binding subunits like calmodulin (CaM) are required. Here we show that CaM is not necessary for activation of Ano1 by Ca2+ for the following reasons. (a) Exogenous CaM has no effect on Ano1 currents in inside-out excised patches. (b) Overexpression of Ca2+-insensitive mutants of CaM have no effect on Ano1 currents, whereas they eliminate the current mediated by the small-conductance Ca2+-activated K+ (SK2) channel. (c) Ano1 does not coimmunoprecipitate with CaM, whereas SK2 does. Furthermore, Ano1 binds very weakly to CaM in pull-down assays. (d) Ano1 is activated in excised patches by low concentrations of Ba2+, which does not activate CaM. In addition, we conclude that reversible phosphorylation/dephosphorylation is not required for current activation by Ca2+ because the current can be repeatedly activated in excised patches in the absence of ATP or other high-energy compounds. Although Ano1 is blocked by the CaM inhibitor trifluoperazine (TFP), we propose that TFP inhibits the channel in a CaM-independent manner because TFP does not inhibit Ano1 when applied to the cytoplasmic side of excised patches. These experiments lead us to conclude that CaM is not required for activation of Ano1 by Ca2+. Although CaM is not required for channel opening by Ca2+, work of other investigators suggests that CaM may have effects in modulating the biophysical properties of the channel.
A review of study designs and statistical methods for genomic epidemiology studies using next generation sequencing.

Results from numerous linkage and association studies have greatly deepened scientists’ understanding of the genetic basis of many human diseases, yet some important questions remain unanswered. For example, although a large number of disease-associated loci have been identified from genome-wide association studies (GWAS) in the past 10 years, it is challenging to interpret these results as most disease-associated markers have no clear functional roles in disease etiology, and all the identified genomic factors only explain a small portion of disease heritability. With the help of next-generation sequencing (NGS), diverse types of genomic and epigenetic variations can be detected with high accuracy. More importantly, instead of using linkage disequilibrium to detect association signals based on a set of pre-set probes, NGS allows researchers to directly study all the variants in each individual, therefore promises opportunities for identifying functional variants and a more comprehensive dissection of disease heritability. Although the current scale of NGS studies is still limited due to the high cost, the success of several recent studies suggests the great potential for applying NGS in genomic epidemiology, especially as the cost of sequencing continues to drop. In this review, we discuss several pioneer applications of NGS, summarize scientific discoveries for rare and complex diseases, and compare various study designs including targeted sequencing and whole-genome sequencing using population-based and family-based cohorts. Finally, we highlight recent advancements in statistical methods proposed for sequencing analysis, including group-based association tests, meta-analysis techniques, and annotation tools for variant prioritization.
Interleukin-1 Receptor Signaling Is Required To Overcome the Effects of Pertussis Toxin and for Efficient Infection- or Vaccination-Induced Immunity against Bordetella pertussis

ABSTRACT Interleukin-1 receptor-deficient (IL-1R−/−) mice are healthy despite being colonized by commensal microbes but are defective in defenses against specific pathogens, suggesting that IL-1R-mediated effects contribute to immune responses against specific pathogenic mechanisms. To better define the role of IL-1R in immunity to respiratory infections, we challenged IL-1R−/− mice with Bordetella pertussis and Bordetella parapertussis, the causative agents of whooping cough. Following inoculation with B. pertussis, but not B. parapertussis, IL-1R−/− mice showed elevated bacterial numbers and more extensive inflammatory pathology than wild-type mice. Acellular B. pertussis vaccines were not efficiently protective against B. pertussis in IL-1R−/− mice. B. pertussis-stimulated dendritic cells from IL-1R−/− mice produced higher levels of tumor necrosis factor alpha (TNF-α) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-γ) and TNF-α but lower levels of IL-10 were detected during B. pertussis infection in IL-1R−/− mice. Since B. parapertussis did not cause severe disease in IL-1R−/− mice, we hypothesized that the extreme requirement for IL-1R involves pertussis toxin (Ptx), which is expressed only by B. pertussis. An isogenic Ptx-deficient B. pertussis strain had only a modest phenotype in wild-type mice but was completely defective in causing lethal disease in IL-1R−/− mice, indicating that the particular virulence of B. pertussis in these mice requires Ptx. Ptx contributes to IL-1β induction by B. pertussis, which is involved in IL-10 induction through IL-1R signaling. IL-10 treatment reduced B. pertussis numbers in IL-1R−/− mice, suggesting that the lower IL-10 responses partially account for the uncontrolled inflammation and bacterial growth in these mice.
A canopy dominant ant affects twig‐nesting ant assembly in coffee agroecosystems

One commonly studied driver of community assembly is the effect of dominant species on subordinate species. Dominant species may impact community assembly during competitive sorting, or recruitment. For ants, important and abundant species in the tropics, several factors may drive community assembly including competition, dispersal, priority effects, and environmental conditions. Although competition is a hallmark of ant ecology, few have examined the influence of patchily distributed dominant ants on other ant species and diversity, especially at the recruitment stage. Here, I consider the impacts of a canopy dominant ant species, Azteca instabilis, and changes in vegetation on twig-nesting ant colony founding and ant community assembly in a coffee agroecosystem. I added artificial nests to coffee plants in areas with and without A. instabilis four times over a year, and then examined the occupation rate and identity of species colonizing nests. I also examined vegetation characteristics of sites where nests were added. The presence of A. instabilis on coffee plants drastically lowered colonization rates, but nest occupation increased with tree density, and with decreasing proportion of Inga spp. trees in the canopy. The presence of A. instabilis limited the number of nests occupied by six of the ten most common species; most rare species, however, were not affected by A. instabilis presence. Richness of colonizing ants in areas with A. instabilis was lower, but these effects did not significantly affect richness across broader scales. Despite large effects on individual species, species composition did not differ greatly in areas with and without A. instabilis, but some vegetation characteristics (basal area and tree richness) were predictive of ant composition. These results suggest that A. instabilis strongly affects founding events especially for common twig-nesting species and that both vegetation and influences from this dominant species affect community assembly of twig-nesting ants at the local scale.
Evaluating User-Adaptive Systems: Lessons from Experiences with a Personalized Meeting Scheduling Assistant

We discuss experiences from evaluating the learning performance of a user-adaptive personal assistant agent. We discuss the challenge of designing adequate evaluation and the tension of collecting adequate data without a fully functional, deployed system. Reflections on negative and positive experiences point to the challenges of evaluating user-adaptive AI systems. Lessons learned concern early consideration of evaluation and deployment, characteristics of AI technology and domains that make controlled evaluations appropriate or not, holistic experimental design, implications of “in the wild” evaluation, and the effect of AI-enabled functionality and its impact upon existing tools and work practices.
Supercapacitor Electrical and Thermal Modeling, Identification, and Validation for a Wide Range of Temperature and Power Applications

Supercapacitors benefit from unique features including high power density, long cycle life, wide temperature operation range, durability in harsh environments, efficient cycling, and low maintenance cost. This paper presents a validated lumped and computationally efficient electrical and thermal model for a cylindrical supercapacitor cell. The electrical model is a two-state equivalent electric circuit model with three parameters that are identified using temporal experiments. The dependence of the parameters on the state of charge, current direction and magnitude (20–200 A), and temperatures ranging from -40 °C to 60 °C is incorporated in the model. The thermal model is a linear 1-D model with two states. The reversible heat generation which is significant in double-layer capacitors is included in the thermal model. The coupling of the two models enables tuning of the temperature-dependent parameters of the electrical model in real time. The coupled electrothermal model is validated using real-world duty cycles at subzero and room temperatures with root-mean-square errors of (82 mV–87 mV) and (0.17 °C–0.21 °C) for terminal voltage and temperature, respectively. This accurate model is implementable in real-time power applications and also thermal management studies of supercapacitor packs.
Policy shaping with human teachers

In this work we evaluate the performance of a policy shaping algorithm using 26 human teachers. We examine if the algorithm is suitable for human-generated data on two different boards in a pac-man domain, comparing performance to an oracle that provides critique based on one known winning policy. Perhaps surprisingly, we show that the data generated by our 26 participants yields even better performance for the agent than data generated by the oracle. This might be because humans do not discourage exploring multiple winning policies. Additionally, we evaluate the impact of different verbal instructions, and different interpretations of silence, finding that the usefulness of data is affected both by what instructions is given to teachers, and how the data is interpreted.
Variation in metapopulation dynamics of a wetland mammal: The effect of hydrology.

Key factors affecting metapopulation dynamics of animals include patch size, isolation, and patch quality. For wetlandassociated species, hydrology can affect patch availability, connectivity, and potentially habitat quality; and therefore drive metapopulation dynamics. Wetlands occurring on natural river floodplains typically have more dynamic hydrology than anthropogenic wetlands. Our overall objective was to assess the multiyear spatial and temporal variation in occupancy and turnover rates of a semiaquatic small mammal at two hydrologically distinct wetland complexes. We livetrapped marsh rice rats (Oryzomys palustris) for 3 yr and >50 000 trap nights at nine wetland patches on the Mississippi River floodplain and 14 patches at a reclaimed surface mine in southern Illinois. We used dynamic occupancy modeling to estimate initial occupancy, detection, colonization, and extinction rates at each complex. Catch per unit effort (rice rats captured/1000 trap nights) was markedly higher at the floodplain site (28.1) than the mining site (8.1). We found no evidence that temperature, rainfall, or trapping effort affected detection probability. Probability of initial occupancy was similar between sites and positively related to patch size. Patch colonization probability at both sites was related negatively to total rainfall 3 weeks prior to trapping, and varied across years differently at each site. We found interacting effects of site and rainfall on extinction probability: extinction increased with total rainfall 3 months prior to trapping but markedly more at the floodplain site than at the mining site. These sitespecific patterns of colonization and extinction are consistent with the rice rat metapopulation in the floodplain exhibiting a habitattracking dynamic (occupancy dynamics driven by fluctuating quality), whereas the mineland complex behaved more as a classic metapopulation (stochastic colonization & extinction). Our study supports previous work demonstrating metapopulation dynamics in wetland systems being driven by changes in patch quality (via hydrology) rather than solely area and isolation.
Rationality and Perspective

An account of rationality should allow us to understand the variety of claims we make using the notion of rationality and its cognates. Here's a simple illustration of this variety. S is at the race track, where the betting odds on three horses A, B and C are the same. S has information that on reflection he would regard as indicating that B is likely to win. However, he hasn't reflected on this evidence, and he instead believes that A will win. But despite what he believes and the evidence he currently possesses, there's other information available (say, information on injuries to A and B) that make it highly probable that C will win. Now imagine three scenes: Scene #1: I'm talking with friend #1 who is confident that A is the slowest horse in the field. I tell her that in all likelihood S is going to bet on A. She shakes her head in wonderment and says, 'That's completely irrational; he must be out of his mind.' I respond, 'No; it's just that he's truly convinced that A will win. And given that he believes this, it's rational for him to bet on A. Indeed, any other bet would patently irrational. It would be betting on a horse that he believes will lose.' Scene #2: A few minutes later, I'm talking with friend #2, who tells me that S is probably going to bet on A, since he seems so sure that A will win. I say to her, 'Maybe so, but given the information he has, it would be rational for him to bet on B. If he were to reflect for a moment on his information, he himself would admit that this is the wise choice, the best bet. He himself would be critical of any other bet.' Scene #3: I'm now talking with friend #3. We each know that the other is aware of the injury reports on horses A and B. We also both know that it's important for S to win his bet, since he has serious debts. We're discussing which bet would be best for him. I say, 'I'm not certain what he's disposed to do, but clearly he should bet on C. Insofar as he needs to win, this is the rational bet for him to make. After all, horse C has the best chance of winning.' In each of the above scenes, I'm evaluating S's decision in a way that we often want to evaluate the decisions of others, and in each of the scenes I
Synthetic Molecular Evolution Approach: Discovery and Characterization of Novel Antiviral Peptides

Peptide entry inhibitors (PEI) interfere with the key steps by which enveloped viruses bind to, fuse with, enter, and eventually infect their target cells. There has been increasing interest in engineering new PEIs and improving their bioactivity to combat rapidly and constantly mutating viruses. Yet the lack of generic molecular design principles has obstructed the development of new PEIs. To circumvent this roadblock, we are developing a synthetic molecular evolution-based approach to select PEIs based on their membrane interactions. Using the Wimley-White interfacial hydrophobicity scale to identify membrane interacting sequences, peptide entry inhibitors have been identified from within several viral fusion proteins. We have hypothesized that some of these peptides interfere with binding and fusion by interacting with directly viral and cellular membranes as well as with hydrophobic portions of viral fusion proteins. This hypothesis leads to the prediction that membrane-active peptides, in general, will inherently have some activity against enveloped viruses, even when those peptides are not derived from viral fusion proteins. To test this idea, we are using cell biology and biophysics to assess and compare the antiviral potency of several families of interfacially active peptides that we have discovered. Based on the results of this characterization we will then use synthetic molecular evolution, consisting of iterative library design and high-throughput screening, to identify PEIs that have the needed antiviral potency to be useful therapeutics.