cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhanced metabolism and mutagenesis of nitrosopyrrolidine in liver fractions isolated from chronic ethanol-consuming hamsters

Abstract The effect of chronic ethanol consumption on the ability of isolated liver fractions to metabolize the carcinogen N -nitrosopyrrolidine (NPY) was examined. Microsomal fractions of treated animals exhibited increased rates of α-hydroxylation of NPY. Similar increases in the specific activities of aniline hydroxylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase, and the specific content of cytochrome P-450 were also observed. In contrast, no differences in the specific activities of benzo( a )pyrene hydroxylase or glucose-6-phosphatase were observed. Liver postmitochondrial supernatants from ethanol-consuming animals were able to produce 5 times more mutants than did control preparations. It is concluded that α-hydroxylation of NPY is probably the mechanism by which NPY is converted to a mutagen and that this pathway can be induced by ethanol.
Effects of Time, Endurance, and Scoring Variables on Tennis Results

Abstract Comparisons were made between match results using the traditional method of scoring tennis matches and match results using the Van Alen Simplified Scoring System (VASSS). Fourteen players from the Florida State University tennis team and 14 students from an intermediate tennis class at the Florida State University participated in the study. Each group of subjects, advanced and intermediate, played two separate round robin tournaments, one using traditional scoring and the other using VASSS. There was no significant difference between the mean match times of the two scoring systems. The variability of match times in the traditional method, however, was significantly greater than the variability of match times in the VASSS method at both ability levels. The same relationship held true for the mean number of points played per match except for a significant difference between the mean number of points played per match at the advanced level. Internal consistency within each tournament was above 90% in...
Survey of industry perspectives on 3D computer animation education

The paper summarizes the results of an online survey of 43 professionals working in the animation industry, including modelers, animators, technical directors, conceptual artists and lighting and texture artists. Respondents were asked to rate the appropriate level of emphasis of 14 topics commonly addressed in academic computer animation programs, ranging from fine arts skills to computer programming. Three relatively non-technical topics were top rated: fundamentals, preproduction and design/layout. There was substantial agreement in rankings among participants, even those with widely varying areas of professional interest. When asked about their own personal educational experiences 25% felt that they had been well prepared, 38% satisfactorily prepared and 37% underprepared.
Decision Support Classification of Geospatial and Regular Objects Using Rough and Fuzzy Sets

In Geospatial Databases, there is often the need to store and manipulate objects with uncertain, fuzzy, or indeterminate boundaries. Both fuzzy sets and rough sets have been used with success in this undertaking. In this paper we explore how we can use both of these techniques to better classify and categorize both regular objects and geospatial objects.
Analyzing Return-on-Investment in Sponsorship: Modeling Brand Exposure, Price and ROI in Formula One Automotive Competition

Determining return-on-investment (ROI) for corporate sponsorship of events, teams, and leagues remains an evolving science. To advance ROI analysis in sponsorship, we utilize data on sponsorship prices and the televised brand exposure of sponsors in Formula One (F1) motor racing. Results validate a strong link between sponsored team performance and both sponsors’ realized brand exposure and price paid, which is also influenced by sponsorship level and congruence factors. Surplus ROI is more likely for sponsors of better performing teams, sponsors that affiliate at a high level and sponsors outside of the automotive industry.
Anaerobic digestion of undiluted simulant human excreta for sanitation and energy recovery in less-developed countries

Abstract Improving access to sanitation is one of the most effective means to improve public health. Anaerobic digestion of high-strength undiluted human simulant excreta was investigated in laboratory systems. The focus was on demonstrating the suitability of using simple unmixed anaerobic digesters for the treatment of a simulant high-strength undiluted human excreta and to quantify the effects of high ammonia concentration on the biogas yield. A maximum biogas yield of 0.44 NLbiogas g− 1COD was obtained in batch experiments, while yields of 0.38 and 0.24 NLbiogas g− 1COD were obtained at 5 and 8 g total ammonia nitrogen (TAN) L− 1, respectively. Using an inoculum acclimated to high ammonia concentrations was critical to successful biogas production at these high TAN concentrations. Stable long-term anaerobic digestion of simulant human excreta at ammonia concentrations ranging from 5.20 to 7.15 g-N L− 1 was obtained in a scaled-down mimic of a low cost floating dome anaerobic digester. Overall, the results demonstrate that anaerobic digestion of undiluted human simulant excreta in simple unmixed digesters is feasible and yields biogas, which is a valuable commodity. When combined with proper hygienization of its effluent, anaerobic digestion could contribute to effective sanitation in developing countries with limited water availability.
The print sources of New Mexican colonial hide paintings

La pintura en piel fue una de las formas mas caracteristicas de la pintura religiosa de Nuevo Mexico. El articulo recopila los conocimientos sobre estas pinturas y examina sus peculiaridades formales para agruparlas de acuerdo a su autoria. Ademas, al identificar las fuentes iconograficas grabadas, tanto europeas como novohispanas, en que estan basadas algunas de las pinturas neomexicanas, la autora amplia los referentes culturales de estas obras.
Characterizing decadal to centennial variability in the equatorial Pacific during the last millennium

[1] The magnitude of sea surface temperature variability in the NINO3.4 region of the equatorial Pacific on decadal and longer timescales is assessed in observational data, state-of-the-art (Coupled Model Intercomparison Project 5) climate model simulations, and a new ensemble of paleoclimate reconstructions. On decadal to multidecadal timescales, variability in these records is consistent with the null hypothesis that it arises from “multivariate red noise” (a multivariate Ornstein-Uhlenbeck process) generated from a linear inverse model of tropical ocean-atmosphere dynamics. On centennial and longer timescales, both a last millennium simulation performed using the Community Climate System Model 4 (CCSM4) and the paleoclimate reconstructions have variability that is significantly stronger than the null hypothesis. However, the time series of the model and the reconstruction do not agree with each other. In the model, variability primarily reflects a thermodynamic response to reconstructed solar and volcanic activity, whereas in the reconstruction, variability arises from either internal climate processes, forced responses that differ from those in CCSM4, or nonclimatic proxy processes that are not yet understood. These findings imply that the response of the tropical Pacific to future forcings may be even more uncertain than portrayed by state-of-the-art models because there are potentially important sources of century-scale variability that these models do not simulate.
Influence of volcanic history on groundwater patterns on the west slope of the Oregon High Cascades.

[1] Spring systems on the west slope of the Oregon High Cascades exhibit complex relationships among modern topography, lava flow geometries, and groundwater flow patterns. Seven cold springs were continuously monitored for discharge and temperature in the 2004 water year, and they were periodically sampled for δ18O, δD, tritium, and dissolved noble gases. Anomalously high unit discharges suggest that topographically defined watersheds may not correspond to aquifer boundaries, and oxygen isotope data reveal that mean recharge elevations for the springs are coincident with extensive Holocene lava fields. The 3He/4He ratios in most of the springs are close to atmospheric, implying shallow flow paths, and aquifer thicknesses are estimated to be 30–140 m. Estimates using 3H/3He data with exponential and gamma distributions yield mean transit times of ∼3–14 years. Recharge areas and flow paths are likely controlled by the geographic extent of lava flows, and some groundwater may cross the Cascade crest.
Abstract A47: MicroRNA-510 as a predictive marker for response to platinum-based chemotherapy in triple negative breast cancer

Breast cancer is a heterogeneous disease with multiple subtypes, which are clinically classified based on the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Associated with the poorest prognosis of all subtypes, triple negative breast cancer (TNBC) is defined as ER-/PR-/HER2-; without these molecular targets, these cancers are insensitive to highly effective targeted therapies and systemic chemotherapy remains the mainstay of treatment for these women. Resent research has shown that platinum chemotherapy agents are particularly active in TNBC, including a clinical trial that demonstrated single agent cisplatin alone can induce response in a subset of TNBC patients. The identification of biomarkers to predict response is required to distinguish patients most likely to benefit from this agent from resistant ones, whom may respond better from other forms of chemotherapy. We have published studies examining the role of miR-510 in breast cancer and observed that miR-510 expression is elevated in tumors when compared to matched non-tumor samples. Drug cytotoxicity assays indicate miR-510 positively correlates with sensitivity to cisplatin in vitro. Furthermore, inhibition of miR-510 causes sensitive breast cancer cell lines to be more resistant in vitro, while overexpression of miR-510 restores sensitivity to cisplatin in resistant breast cancer cell lines both in vitro and in vivo. Recent mechanistic studies have revealed that cisplatin activates the ΔNp63/TAp73 apoptotic pathway specifically in in TNBC with p53 mutations (∼60% of all TNBCs). We have validated peroxiredoxin 1 (Prdx1) as a direct target of miR-510 and studies have also indicated that Prdx1 is a negative regulator of the ΔNp63/Tap73 pathway, suggesting that miR-510 may mediate sensitivity to cisplatin through the negative regulation of Prdx1. We demonstrate an increase in the activation of this pathway in TNBC cells expressing miR-510 upon cisplatin treatment. Based on these data we propose that elevated levels of miR-510 mediates cisplatin sensitivity and that it may serve as a non-invasive biomarker to predict response to cisplatin in TNBC patients. To this end, we have shown by qPCR that miR-510 levels are detectable in serum samples from a subset of human breast cancer patients, and further studies will assess positive correlations between miR-510 expression and cisplatin sensitivity. Citation Format: Qi Jin Guo, Jamie N. Miils, Natalie Mason, Savannah G. Bandurraga, Lourdes M. Nogueira, Rita Kramer, David P. Turner, Victoria J. Findlay. MicroRNA-510 as a predictive marker for response to platinum-based chemotherapy in triple negative breast cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A47.
Subcritical barrier AlN/GaN E/D‐mode HFETs and inverters

Enhancement- and depletion-mode AlN/GaN HFETs have been fabricated with a subcritical barrier design: a two-dimensional electron gas (2DEG) is induced in the highly resistive as-grown heterostructure when a suitable capping material is deposited over the ultrathin AlN barrier. In this bottom-up approach 2DEGs can be locally induced by patterned cap layers on subcritical barrier AlN/GaN heterostructures, which can enable the monolithic integration of enhancement- and depletion-mode HFETs. An inverter circuit with 1.5 nm ultrathin AlN barrier E- and D-mode HFETs was successfully demonstrated with reasonable voltage transfer characteristics, noise margin, and gain. To our best knowledge this is the first reported inverter based on subcritical barrier III― V nitride heterostructures. Integration of E- and D-mode HFETs in a subcritical barrier AlN/GaN heterostructure, where n 2DEG ∼ 0 in the as-grown structure. A patterned cap locally enhances 2DEG at the AlN/ GaN hetero-interface due to barrier lowering. It is an additive approach in contrast to the conventional gate recessing technique.
Mechanism of renal glycosuria in ACTH-treated premature infants.

ConclusionsGlycosuria resulting from ACTH administration in premature infants is due to an imbalance of glomerulotubular function demonstrated by a rise in GFR/TmG ratio. The cause of the rise in this ratio varied and was due either to a disproportionate rise in glomerular nitration rate or fall in glucose Tm. The nonglycosuric ACTH-treated infants did not show this rise in the GFR/TmG ratio.
Extrapulmonic stenosis of the pulmonary veins.

A case is reported of a 6-year-old boy who had developed pulmonary hypertension because of obstruction to the pulmonary venous flow by severe stenosis of the pulmonary veins at their junction with the left atrium. The development of collateral circulation through the bronchial vessels led to early, severe hemoptysis. The course was complicated by the development of pulmonary arterial and venous thrombi and hypertensive arteritis.
Simulation of non-Markovian systems

A generalized semi-Markov process provides a stochastic process model for a discrete-event simulation. This representation is particularly useful for non-Markovian systems where it is nontrivial to obtain recurrence properties of the underlying stochastic processes. We develop "geometric trials" arguments which can be used to obtain results on recurrence and regeneration in this setting. Such properties are needed to establish estimation procedures based on regenerative processes. Applications to modeling and simulation of ring and bus networks are discussed.
A Blueprint for GNEP Advanced Burner Reactor Startup Fuel Fabrication Facility

Abstract The purpose of this article is to identify the requirements and issues associated with design of GNEP Advanced Burner Reactor Fuel Facility. The report was prepared in support of providing data for preparation of a NEPA Environmental Impact Statement in support the U.S. Department of Energy (DOE) Global Nuclear Energy Partnership (GNEP). One of the GNEP objectives was to reduce the inventory of long lived actinide from the light water reactor (LWR) spent fuel. The LWR spent fuel contains Plutonium (Pu)-239 and other transuranics (TRU) such as Americium-241. One of the options is to transmute or burn these actinides in fast neutron spectra as well as generate the electricity. A sodium-cooled Advanced Recycling Reactor (ARR) concept was proposed to achieve this goal. However, fuel with relatively high TRU content has not been used in the fast reactor. To demonstrate the utilization of TRU fuel in a fast reactor, an Advanced Burner Reactor (ABR) prototype of ARR was proposed, which would necessarily be started up using weapons grade (WG) Pu fuel. The WG Pu is distinguished by relatively highest proportions of Pu-239 and lesser amount of other actinides. The WG Pu was assumed to be used as the startup fuel along with TRU fuel in lead test assemblies. Because such fuel is not currently being produced in the US, a new facility (or new capability in an existing facility) was being considered for fabrication of WG Pu fuel for the ABR. It was estimated that the facility will provide the startup fuel for 10–15 years and would take 3–5 years to construct.
Global-to-Regional Nested Grid Climate Simulations in the GFDL High Resolution Atmospheric Model

AbstractA two-way nested grid version of the Geophysical Fluid Dynamics Laboratory High Resolution Atmosphere Model (HiRAM) has been developed that uses simple methods for providing nested grid boundary conditions and mass-conserving nested-to-global communication. Nested grid simulations over the Maritime Continent and over North America were performed, each at two different resolutions: a 110-km mean grid cell width refined by a factor of 3, and a 50-km mean grid cell width refined by a factor of 2. Nested grid simulations were compared against uniform-resolution simulations, and against reanalyses, to determine the effect of grid nesting on both the modeled global climate and the simulation of small-scale features.Orographically forced precipitation was robustly found to be simulated with more detail and greater realism in a nested grid simulation compared with when only the coarse grids were simulated alone. Tropical precipitation biases were reduced in the Maritime Continent region when a nested grid...
Interaction of levodopa and cues on voluntary reaching in Parkinson's disease.

The bradykinesia associated with Parkinson's disease (PD) can be improved by both levodopa and the use of external cues. We examined the combined effect of levodopa and external cueing on the voluntary reaching movements of individuals with PD. Nine subjects with PD and nine matched controls were studied reaching to a ball target. Subjects with PD were studied after being off levodopa overnight and again on their morning dose. Kinematic data were collected as all subjects made both accurate and fast reaches under two different cue conditions: noncued (self-initiated) and cued (triggered by a light). Subjects with PD reached more slowly than controls under all conditions. PD subjects increased their reach velocity and decreased movement time after taking levodopa and also when moving to a cue. However, the effects of levodopa and cueing were not additive. Instead, levodopa improved reach velocity to a greater extent in the noncued vs. cued condition. We also found that levodopa improved accurate (self-paced) reaches more than fast reaches. These data suggest that levodopa may preferentially improve voluntary reaches that are more internally generated.
Age Comparisons in Workplace Sexual Harassment Perceptions

Few studies have systematically examined the influence of perceivers’ age on perceptions of sexual harassment. We sought to fill this gap, determine whether sexist attitudes mediate relations between age and sexual harassment perceptions, and whether relations between gender, sexist attitudes and perceptions are moderated by age. Results from an age-stratified sample of 965 students and staff employees at a US Midwestern university found a positive relationship between age and sexual harassment perceptions. Hostile sexism partially mediated this relationship, but age did not moderate correlations with gender or sexist attitudes. College-aged samples are less sensitive to harassment than older-aged samples, but the validity of other predictors of sexual harassment perceptions, such as gender and sexist attitudes, remains intact regardless of sample age.
'Locusts and Wild Honey' (Mk 1.6c aNd Mt. 3.4C): the Status Quaestionis Concerning the Diet of John the Baptist:

This article analyzes of Synoptic passages pertaining to John the Baptist’s diet and reviews the history of biblical scholarship on the subject from Erasmus to the present.
Determination of Selectivity Coefficients of Ion Selective Electrodes by Continuous Variation Method

A new method for the determination of the selectivity coefficient of an ion selective electrode is proposed. In the proposed method, a series of mixed solutions of the primary ion i and interfering ion j is prepared in which the sum of the logarithm of i concentration and logarithm of j concentration is kept constant. The potential of the electrode, E, is measured for the series of the mixed solutions. The result is plotted with the activity of i, ai, as abscissa against E on semi-logarithmic graph paper. The activity at the intersection of two extrapolated linear parts of the log ai-E curve is determined. From the activity at the intersection of the primary ion, the selectivity coefficient is calculated. The proposed method was applied to the determination of selectivity coefficients of fluoride, chloride, bromide and potassium selective electrodes. The selectivity coefficients determined by the proposed method, named "continuous variation method", agreed with those obtained with the conventional mixed solution method.
Biology and pathobiology of cardiac connexins: From cell to bedside

This paper, presented on the occasion of the 1st Annual Douglas Zipes Lecture at the 2005 Scientific Sessions of the Heart Rhythm Society, briefly reviews current knowledge on the role of gap junctions in normal cardiac electrophysiology and the contributions of gap junction remodeling in the pathogenesis of malignant ventricular arrhythmias and sudden cardiac death. It highlights recent advances and new research directions in gap junction biology.
Eastern Laurentia in Rodinia: constraints from whole-rock Pb and U/Pb geochronology

Abstract Whole-rock Pb isotopic signatures and U/Pb geochronology refute a Rodinian correlation of northeastern Laurentia and proto-Andean Amazonia. According to this previously proposed model, the Labrador–Scotland–Greenland Promontory (LSGP) of northeastern Laurentia collided with the proto-Andean margin of Amazonia, at the Arica Embayment, during the Grenville/Sunsas Orogeny (ca. 1.0 Ga). Links between the two margins were based upon the correlation of the LSGP with Arequipa-Antofalla Basement (AAB), a Proterozoic block along the proto-Andean margin of Amazonia adjacent to the Arica Embayment. Specifically, similarities in 1.8–1.0 Ga basement rocks in both regions suggested that the AAB was originally a piece of the LSGP. Furthermore, similarities in unique, post-collisional, but pre-rift, glacial sedimentary sequences also supported a link between the AAB and LSGP. Tests of these apparent similarities fail to support correlation of the AAB and the LSGP and, thus, eliminate a direct link between northeastern Laurentia and southwestern Amazonia in Rodinia. However, Pb isotopic compositions and U/Pb geochronology provide the basis for two new correlations, namely, (1) the ca. 1.3–1.0 Ga basement in the central and southern Appalachians may be an allochthonous block that was transferred to Laurentia from Amazonia at ca. 1.0 Ga, and (2) an allochthonous AAB may be a piece of the Kalahari Craton that was transferred to Amazonia at ca. 1.0 Ga. Based on these new correlations and a previously proposed Grenvillian connection between southern Laurentia (Llano) and Kalahari, we propose that Amazonia may have collided with a contiguous southeastern Laurentia/Kalahari margin at ca. 1.0 Ga.
Specialist versus generalist insect herbivores and plant defense

There has been a long-standing hypothesis that specialist and generalist insects interact with plants in distinct ways. Although many tests exist, they typically compare only one species of each, they sometimes confound specialization and feeding guild, and often do not link chemical or transcriptional measures of the plant to actual resistance. In this review, we synthesize current data on whether specialists and generalists actually differ, with special attention to comparisons of their differential elicitation of plant responses. Although we find few consistencies in plant induction by specialists versus generalists, feeding guilds are predictive of differential plant responses. We outline a novel set of predictions based on current coevolutionary hypotheses and make methodological suggestions for improved comparisons of specialists and generalists.
Clone Detection in Sensor Networks with Ad Hoc and Grid Topologies

In cloning attacks, an adversary captures a sensor node, reprograms it, makes multiple copies, and inserts these copies, into the network. Cloned nodes subvert sensor network processing from within. In a companion paper [2], we show how to detect and remove clones from sensor networks using random key predistribution security measures. Keys that are present on the cloned nodes are detected by using authentication statistics based on key usage frequency. For consistency with existing random key predistribution literature, and ease of explanation, the network in that paper used an Erdos-Renyi topology. In the Erdos-Renyi topology, the probability of connection between any two nodes in the network is uniform. Since the communications ranges of sensor nodes are limited, this topology is flawed. This article applies the clone detection approach from [2] to more realistic network topologies. Grid and ad hoc topologies reflect the node connectivity patterns of networks of nodes with range limits. We provide analytical methods for choosing detection thresholds that accurately detect clones. We use simulations to verify our method. In particular we find the limitations of this approach, such as the number of nodes that can be inserted without being detected.
Endogenous synthesis of galactose in normal men and patients with hereditary galactosaemia

Despite restricted ingestion of lactose, patients with galactose-1-phosphate uridyltransferase deficiency have raised concentrations of galactose metabolites in blood and urine. Endogenous production of galactose may underlie this phenomenon. Using isotopically labelled galactose in a continuous intravenous infusion, we employed the steady-state flux method to calculate endogenous galactose production rate in three normal men and three patients with classic galactosaemia. We found that galactosaemic patients and normal subjects synthesise gram quantities of galactose per day. The rate of synthesis ranged from 0.53-1.05 mg/kg per h. Endogenous production of galactose may be an important factor in the pathogenesis of the complications of the brain and ovary, and could explain the persistent elevation of galactose metabolites in patients despite dietary restriction of galactose.
Parallel labeling experiments and metabolic flux analysis: Past, present and future methodologies

Radioactive and stable isotopes have been applied for decades to elucidate metabolic pathways and quantify carbon flow in cellular systems using mass and isotope balancing approaches. Isotope-labeling experiments can be conducted as a single tracer experiment, or as parallel labeling experiments. In the latter case, several experiments are performed under identical conditions except for the choice of substrate labeling. In this review, we highlight robust approaches for probing metabolism and addressing metabolically related questions though parallel labeling experiments. In the first part, we provide a brief historical perspective on parallel labeling experiments, from the early metabolic studies when radioisotopes were predominant to present-day applications based on stable-isotopes. We also elaborate on important technical and theoretical advances that have facilitated the transition from radioisotopes to stable-isotopes. In the second part of the review, we focus on parallel labeling experiments for 13C-metabolic flux analysis (13C-MFA). Parallel experiments offer several advantages that include: tailoring experiments to resolve specific fluxes with high precision; reducing the length of labeling experiments by introducing multiple entry-points of isotopes; validating biochemical network models; and improving the performance of 13C-MFA in systems where the number of measurements is limited. We conclude by discussing some challenges facing the use of parallel labeling experiments for 13C-MFA and highlight the need to address issues related to biological variability, data integration, and rational tracer selection.
Community Youth Development Professionals: Providing the Necessary Supports in the United States

This paper explores the educational opportunities available to community youth development professionals in the United States. Given the complexity of the needs of today’s young people, it is both timely and prudent to increase the type, quality, and quantity of educational experiences available to community youth development professionals. Researchers, practitioners, policymakers, and funding agencies have all begun to explore the importance of providing educational opportunities to community youth development professionals. The findings of this investigation indicate a need for a comprehensive multidimensional educational system to provide community youth development professionals with the knowledge and skills essential to successfully meet the challenges they encounter in their daily work.
Mucopolysaccharidosis type I (Hurler syndrome): Linkage disequilibrium indicates the presence of a major allele

Two polymorphisms exist in the α-l-iduronidase (IDUA) gene, the gene that is defective in mucopolysaccharidosis type I (MPS I), viz. aKpnI polymorphism and a variable number of tandem repeats (VNTR) polymorphism with three common alleles. The analysis of allele and haplotype frequencies for these two polymorphisms in the normal population and in MPS I patients revealed the presence of linkage disequilibrium. The frequency of the 2,2 (VNTR,KpnI) allele in MPS I patients was 57% compared with only 37% in the normal population. The implications for the presence of a major MPS I allele and the ability to predict patient phenotype are discussed.
Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat model

The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation.
Fast Hopping Injection Locked Frequency Generation for UWB

We present a novel injection locking frequency generation scheme for UWB systems. In the MBOA-UWB specification, the critical constraint on the frequency synthesizer is the band switching time (< 9.5 ns). In this paper we derive analytical expressions for the transient behavior of injection locked oscillators (ILO) and describe the design constraints on frequency settling of ILOs. We show that they are capable of UWB compliant fast frequency hopping. ILO based frequency synthesizers have a number of advantages over traditional fast hopping LO generation techniques. In particular, it eliminates the need for multiple PLLs and single-sideband (SSB) mixers reducing power consumption and eliminating parasitic spurs.
Artificial urinary sphincter placement in men after cystectomy with orthotopic ileal neobladder: continence, complications, and quality of life.

Objectives. To review our experience regarding the overall efficacy and safety of an artificial urinary sphincter (AUS) in men with stress urinary incontinence (SUI) after cystoprostatectomy with an orthotopic ileal neobladder. Methods. We performed a retrospective review of 5 men who underwent placement of an AUS (AMS 800) for severe SUI after radical cystectomy with an orthotopic ileal neobladder. Incontinence symptoms and quality of life were quantified using two validated continence questionnaires (Urogenital Distress Inventory Short Form and Incontinence Impact Questionnaire Short Form) and a brief addendum questionnaire. The degree of continence, perioperative and postoperative complications and infections, symptom distress, quality of life, and patient satisfaction were compared before and after AUS placement. Results. Complete (0 pads per day) or social (1 pad or less per day) continence was reported in 5 of 5 patients after AUS placement. The average pad usage significantly decreased from 6.2 to 0.6 per day (P <0.001). No significant perioperative or postoperative complications or infections were noted. Symptom distress, quality of life, and patient satisfaction were significantly improved after AUS placement (P <0.01, <0.0001, and <0.001, respectively). Conclusions. With short-term follow-up and a limited number of patients, the placement of an AUS for treatment of SUI after bladder substitution is well tolerated and reliable and has a positive impact on patients’ quality of life.
Reparameterizing the pattern mixture model for sensitivity analyses under informative dropout.

Summary. Pattern mixture models are frequently used to analyze longitudinal data where missingness is induced by dropout. For measured responses, it is typical to model the complete data as a mixture of multivariate normal distributions, where mixing is done over the dropout distribution. Fully parameterized pattern mixture models are not identified by incomplete data; Little (1993, Journal of the American Statistical Association88, 125–134) has characterized several identifying restrictions that can be used for model fitting. We propose a reparameterization of the pattern mixture model that allows investigation of sensitivity to assumptions about nonidentified parameters in both the mean and variance, allows consideration of a wide range of nonignorable missing-data mechanisms, and has intuitive appeal for eliciting plausible missing-data mechanisms. The parameterization makes clear an advantage of pattern mixture models over parametric selection models, namely that the missing-data mechanism can be varied without affecting the marginal distribution of the observed data. To illustrate the utility of the new parameterization, we analyze data from a recent clinical trial of growth hormone for maintaining muscle strength in the elderly. Dropout occurs at a high rate and is potentially informative. We undertake a detailed sensitivity analysis to understand the impact of missing-data assumptions on the inference about the effects of growth hormone on muscle strength.
Do insurance activities enhance the performance of financial services holding companies

Stiroh and Rumble (2006) and Yeager et al. (2007) have argued that extension of banks into nonbanking activities produces no diversification benefits for financial services holding companies (FSHCs) eligible to consolidate banking and insurance products. We investigate the effect of aggregate nonbank activities, as well as two main areas of insurance business, namely agency and underwriting enterprise, on the risk-adjusted performance of FSHCs. Our sample includes a quarterly panel data of FSHCs over the period 2003–2011. We find that the effect of FSHCs’ entry into agency insurance activities on their risk-adjusted returns is dependent on their size; it is positive for FSHCs in the top quartile of our sample (assets greater than $4.495 billions), but negative for smaller and mid-size FSHCs. The effect of underwriting insurance activities on risk-adjusted returns is generally negative or statistically insignificant, except for some of the largest-size firms.
Controversies in defining cardiac antibody-mediated rejection: Need for updated criteria

Recent years have seen a rising awareness of the significance of cardiac antibody-mediated rejection (AMR) as a result of its formal recognition by the International Society for Heart and Lung Transplantation. New insights on the pathology and clinical behavior of cardiac AMR are at odds with current diagnostic guidelines. This perspective examines some of the contentious and unresolved issues in cardiac AMR as the transplant community makes concrete steps towards updating its defining criteria.
The influence of induced depressed mood on visual recognition thresholds: Predictive ambiguity of associative network models of mood and cognition

Eighteen undergraduates given a negative mood verbal induction procedure had visual recognition duration thresholds that were significantly lower for dysphoric content words than for elated content words. They also recognized elated content words at briefer exposures than neutral content words, and at briefer exposures than did 18 undergraduates who received a neutral mood induction, who did not show threshold differences across word types. Thus, a negative mood induction procedure facilitated recognition of not only dysphoric content but also elated content stimuli. These findings further demonstrate the breadth of the effects of mood on cognition, and they also demonstrate the predictive ambiguity of associative network models of cognition.
Interactions between glial progenitors and blood vessels during early postnatal corticogenesis: blood vessel contact represents an early stage of astrocyte differentiation.

The post-neurogenic period in the mammalian neocortex is characterized by the growth of astrocyte and oligodendrocyte populations and their incorporation into the network of the developing central nervous system (CNS). Many of these glial cells originate as progenitors in the subventricular zone (SVZ) and then migrate into white and gray matter before differentiating. What determines the specific cellular fate of progenitors in vivo is not known, however. In examining the early stages of gliogenesis from progenitors in the SVZ, we noted that interactions with cortical blood vessels took place at what appeared to be an early stage of glial differentiation. We have examined in more detail the interactions of progenitors with blood vessels in the early postnatal rat neocortex after labeling progenitors in vivo with a LacZ-encoding retrovirus. These early interactions are accompanied by an increase in intermediate filament expression, consistent with astrocytic differentiation. Because astrocytes interact with blood vessels and pia, we suggest that such contact represents an early stage in astrocytic differentiation. Furthermore, since angiogenesis and astrogenesis occur over a similar period, the growth of blood vessels may even play a role in the selection of astrocytic fate by a progenitor. As vessel growth slows, fewer progenitors may be directed toward an astrocyte fate, allowing more to differentiate into oligodendrocytes, perhaps explaining the shift from astrocyte genesis to oligodendrocyte genesis during early postnatal cortical development. J. Comp. Neurol. 387:537–546, 1997. © 1997 Wiley-Liss, Inc.
Micronucleus, chromosome aberration, and small-colony TK mutant analysis to quantitate chromosomal damage in L5178Y mouse lymphoma cells.

Abstract In testing the hypothesis that the small-colony thymidine kinase-deficient mutants of L5178Y/TK +/− −3.7.2C mouse lymphoma cells represent an estimate of the clastogenicity of test chemicals, we have been performing gross aberration analysis. The present study was initiated to determine if the cytokinesis block method of micronucleus analysis could be performed in mouse lymphoma cells and to compare 3 different endpoints of clastogenicity: the number of metaphases with aberrations, number of binucleates with micronuclei, and small-colony TK mutant frequency. In this study, 12 compounds having varying clastogenic potencies were evaluated. As would be expected, the 3 endpoints vary in the relative magnitude of the quantitated response. This difference likely results from the types of clastogenic damage detected by each endpoint. Of the 3 endpoints tested, only the small-colony TK mutant frequency measures events compatible with long-term cell survival.
Inhibition of heat-shock protein 90 reduces Ebola virus replication

Ebola virus (EBOV), a negative-sense RNA virus in the family Filoviridae, is known to cause severe hemorrhagic fever in humans and other primates. Infection with EBOV causes a high mortality rate and currently there is no FDA-licensed vaccine or therapeutic treatment available. Recently, heat-shock protein 90 (Hsp90), a molecular chaperone, was shown to be an important host factor for the replication of several negative-strand viruses. We tested the effect of several different Hsp90 inhibitors including geldanamycin, radicicol, and 17-allylamino-17-demethoxygeldanamycin (17-AAG; a geldanamycin analog) on the replication of Zaire EBOV. Our results showed that inhibition of Hsp90 significantly reduced the replication of EBOV. Classic Hsp90 inhibitors reduced viral replication with an effective concentration at 50% (EC50) in the high nanomolar to low micromolar range, while drugs from a new class of Hsp90 inhibitors showed markedly more potent inhibition. These compounds blocked EBOV replication with an EC50 in the low nanomolar range and showed significant potency in blocking replication in primary human monocytes. These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection.
School choice and perceived school quality

Abstract School choice programs–school vouchers, open enrollment, tuition tax credits and charter schools–reduce the cost of sending children to a school different than their assignment. Previous literature shows support for school choice is weaker in objectively high-performing school districts. We show that people’s opinions about school quality matter at least as much as objective measures like proficiency tests. We find support for school choice is lower when people think their assigned public school district is good (or even the typical public school district in the state); support for choice is higher when people think their nearest private school is good.
The effects of chronic hypoxia on the myocardial cell of normotensive and hypertensive rats.

Myocardial cellular and subcellular adaptations associated with chronic hypoxia were determined in 16 week old male normotensive Wistar-Kyoto, spontaneously hypertensive and aortic constricted rats. The animals were exposed to six weeks of hypobaric hypoxia at a simulated altitude of 6,100 (m), and their glutaraldehyde perfuse-fixed hearts compared to normoxic controls. Exposure to hypoxia abolished the hypertension associated with the spontaneously hypertensive and aortic constricted groups and reduced the mean heart rate in all three hypoxic groups. The magnitude of hypertrophy was significant and comparable in all three groups, based on heart weight and left ventricular fiber diameter measurements. While capillary density was significantly reduced in the spontaneously hypertensive and aortic constricted rats, exposure to hypoxia facilitated an absolute increase in the number of capillaries of the hypoxic spontaneously hypertensive and aortic constricted rats. In the hypoxic control group, the capillary density was maintained despite a 20% increase in the muscle fiber diameter, indicating a proliferation of the capillary bed in proportion to the increase in muscle mass. The myocytes in all hypoxic groups were characterized by deep invaginations of the cell membrane and an increase in the number of pinocytotic vesicles. Stereological analyses of the myocytes revealed a statistically significant decrease in the mitochondria/myofibril volume ratio in animals with pressure overload. This ratio was not significantly altered when the animals were subjected to chronic hypoxia. However, there was an increase in the number of mitochondrial profiles and a decrease in the size of individual profiles in all hypoxic groups when compared to the control group. These findings suggest that cardiac hypertrophy associated with chronic hypobaric hypoxia, unlike hypertrophy due to pressure overload, is associated with a number of structural adaptations which may aid the heart in functioning in the hypoxic environment.
Theory for the sequence of human and rat enamel dissolution by acid and by EDTA: a correlated scanning and transmission electron microscope study.

Abstract Prepared human enamel surfaces were treated with either EDTA or dilute HCl and viewed in the SEM. After re-embedment, the samples were thin sectioned and examined in the TEM. The results indicate that individual enamel crystals are attacked in the same fashion by both EDTA and HCl: the core of the crystal is dissolved from the ends followed by a shortening of the remaining crystal shell along its c-axis. At the prism level, however, the effects of EDTA and acid differ strikingly. The attack of EDTA depended on the size of the spaces between crystals and, therefore, was most pronounced at the periphery of the prism head. The EDTA created an arcuate cleft which widened with time and eventually presented a topography of isolated prism cores as seen in the SEM. In the TEM, it became evident that the crystals in these resistant cores were tightly packed and unaffected, except for a very thin layer of crystals along the outside which were partially dissolved. The acid-etch pattern depended primarily on crystal orientation. The crystals arranged parallel to the attack were the most vulnerable due to a weaker core along the entire c-axis. Therefore, surfaces presenting prisms in cross section showed preferential dissolution of prism cores. This resulted in a honeycomb topography as seen in the SEM. In the TEM, it was observed that nearly all crystals for some distance beneath the surface were attacked. A double row of crystals bordering a narrow cleft along the arcuate prism periphery presented an exception. These crystals appeared larger, more hexagonal and more acid resistant than the others. The observed effects of the acid led to a theory which allows for partial depletion of mineral content while the enamel maintains its gross structure. Although the effect of EDTA also fits into this system, it is limited to only a few layers of crystals at a time.