cssi/SciSciGPT-SciSciNet huggingface dataset:
Robotic Salvage Prostatectomy: a Contemporary Review

We sought to review the appropriate patient selection criteria, available clinical literature, technical modifications, and future directions associated with the use of robotic technology to perform salvage robotic-assisted radical prostatectomy (SRARP). Recent studies have investigated the emerging role of SRARP following primary focal therapies, imaging technologies for preoperative staging and risk assessment, and novel bioengineering and technical modifications to improve postoperative functional outcomes. SRARP represents a potentially curative but underutilized treatment for men who develop localized recurrence of prostate cancer (PCa) following primary radiotherapy treatment or primary focal therapy. While SRARP may be associated with potentially significant complications including rectal injury, erectile dysfunction, and stress urinary incontinence, several centers have published their experience with the procedure and several technical modifications to the standard RALP have been utilized to reduce the risk of these potential treatment side effects. Further standardization of pathology reporting, novel technological and imaging advances, and multi-institutional collaboration will be necessary to improve future SRARP outcomes.
Real-world experience of suture-based closure devices: Insights from the FDA Manufacturer and User Facility Device Experience.

Objectives We analyzed post-marketing surveillance data from the United States Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for suture-based vascular closure devices (VCDs) - Perclose ProGlide (Abbott, Chicago, Illinois) and Prostar XL (Abbott). Background Suture-based VCDs are mostly used for large-bore femoral arterial access-site closure. Real-world, contemporary experience on the most commonly reported complications and modes of failure associated with these devices is limited. Methods Post-marketing surveillance data from the FDA MAUDE database, for the ProGlide system and for the Prostar XL system, were analyzed, yielding 827 Perclose ProGlide reports and 175 Prostar XL reports. Results Of the 827 reports of major complications involving the Perclose ProGlide devices, 404 reports involved injury, and one involved death related to the device. In the Prostar XL analysis, 94 reports involved injury, and one involved death. Bleeding from vessel injury was the most common adverse outcome described with both devices, followed by hematoma and thrombus. Surgical repair was the most commonly used treatment strategy. In terms of device malfunction, suture-related malfunction (212 reports) was most commonly seen in the Perclose ProGlide group, while failed deployment was most commonly seen in the Prostar XL group. Conclusions Our analysis of the MAUDE database demonstrates that in real-world practice, suture-based VCDs were found to be associated with complications, including vascular injury, difficulties with the device itself, and even death. Ongoing user education and pre-procedural patient selection are important to minimize risks associated with suture-based vascular closure devices.
JammingBird: Jamming-Resilient Communications for Vehicular Ad Hoc Networks

Current data-driven intelligent transportation systems are mainly reliant on IEEE 802.11p to collect and exchange information. Despite promising performance of IEEE 802.11p in providing low-latency communications, it is still vulnerable to jamming attacks due to the lack of a PHY-layer countermeasure technique in practice. In this paper, we propose JammingBird, a novel receiver design that tolerates strong constant jamming attacks. The enablers of JammingBird are two MIMO-based techniques: Jamming-resistant synchronizer and jamming suppressor. Collectively, these two new modules are able to detect, synchronize, and recover desired signals under jamming attacks, regardless of the PHY-layer technology employed by the jammers. We have implemented JammingBird on a vehicular testbed and conducted extensive experiments to evaluate its performance in three common vehicular scenarios: Parking lots (0~15 mph), local traffic areas (25~45 mph), and highways (60~70 mph). In our experiments, while the jamming attacks degrade the throughput of conventional 802.11p-based receivers by 86.7%, JammingBird maintains 83.0% of the throughput on average. Experimental results also show that JammingBird tolerates the jamming signals with 25 dB stronger power than the desired signals.
Taking the Pulse of POCUS: The State of Point-of-Care Ultrasound at a Pediatric Tertiary Care Hospital

We aim to quantify and categorize point-of-care ultrasound (POCUS) usage by pediatric practitioners and trainees at our tertiary care center, and assess the degree of interest from pediatric residents, fellows, and program leaders for integrating POCUS into their training. Data was collected via online survey, evaluating the current use of POCUS in clinical decision making, desire for further formal training, and opinions on the importance of POCUS to future clinical practice. In total, 14 program directors/assistant program directors (PD/APDs) representing 10 of 15 training programs, 30 of 95 fellows representing 9 of 15 fellowships, and 32 of 82 residents responded. From PD/APDs, only 2 of the programs reported active use POCUS for clinical decision making, but 13 of the fellows and 9 residents reported doing so. In regard to desire for a formal POCUS program, 30.8% of PD/APDs, 43.8% of fellows without current curricula, and 87.5% of residents were interested in participating in such a program. When considering specialty, some non-acute care-based PD/APDs and fellows at our institution felt that POCUS was important to future practice. Pediatric subspecialty PD/APDs and their fellows had divergent outlooks on the importance of POCUS in future practice. Finally, an overwhelming majority of residents at our institution expressed a desire to learn, and half believing it will be important to future practice. Based on the degree of interest, medicolegal considerations, and trajectory of patient care, pediatric residency and fellowship programs should strongly consider integrating POCUS education into their curricula.
The American Political Economy: Markets, Power, and the Meta Politics of US Economic Governance

This article provides an overview of the emerging field of American political economy (APE). Methodologically eclectic, this field seeks to understand the interaction of markets and government in A...
Lesbian- and bisexually-identified women's use of lubricant during their most recent sexual event with a female partner: Findings from a nationally representative study in the United States

Abstract Purpose: While previous research suggests that lubricant use may be common among lesbian- and bisexually-identified women, it remains unclear from this research whether lubricant was being used with a male or female partner. The present study explores the behavioral, emotional, situational, and relational aspects of lesbian- and bisexually-identified women's lubricant use during their most recent female-partnered sexual event. Methods: Nationally representative data was collected as part of the 2012 National Survey of Sexual Health and Behavior (NSSHB). The 2012 NSSHB had an oversample of lesbian, gay, and bisexual (LGB) individuals. Participants were included in the present study if they identified as a lesbian or bisexual women and indicated that their most recent sexual partner was a female. Participants were asked a variety of questions about the context and experience of lubricant use during this event. Results: Nearly a quarter (21.9%, n=32) of the participants reported that they used a lub...
The late cardiopulmonary effects of childhood pneumonectomy.

Eight patients studied 1-14 years after pneumonectomy performed during childhood demonstrated moderate overinflation of the lung with minimal restriction of ventilatory functions. Carbon monoxide diffusing capacity was greater than predicted and the ratio, V C /V A , was increased indicating overdistention of the pulmonary capillary bed after pneumonectomy. Pulmonary arterial pressure was high normal at rest and elevated with exercise; pulmonary resistance was normal at rest but did not decrease with exercise. The pressure changes were attributed to the entire cardiac output flowing through the single lung. Pneumonectomy in childhood performed for unilateral pulmonary disease is associated with minimal changes in cardiopulmonary performance which does not limit normal activities.
The role of insulin receptor autophosphorylation in signal transduction.

We have examined the role of autophosphorylation in insulin signal transmission by oligonucleotide directed mutagenesis of seven potential tyrosine autophosphorylation sites in the human insulin receptor. Chinese hamster ovary cells transfected with these receptors were analyzed for insulin stimulated 2-deoxyglucose uptake, thymidine incorporation, endogenous substrate phosphorylation, and in vitro kinase activity. We found that phosphorylation on tyrosine residues 953, 1316, and 1322 were not necessary for receptor-mediated signal transduction. Mutation of tyrosine 960 reduced but did not abolish the signaling capabilities of the receptor. Finally, the simultaneous mutation of tyrosine residues 1146, 1150, and 1151 (the numbering system is that of Ullrich et al. (Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L. M., Dull, T. J., Gray, A., Coussens, L., Liao, Y. C., Tsubokawa, M., Mason, A., Seeburg, P.H., Grunfeld, C., Rosen, O. M., and Ramachandran, J. (1985) Nature 313, 756-761) resulted in a biologically inactive receptor, suggesting that the insulin receptor can be inactivated by removal of key autophosphorylation sites.
Acoustic Lenses and Low-Velocity Fluids for Improving Bragg-Diffraction Images

Horizontal resolution in a Bragg-diffraction imaging system can be substantially improved by inserting a cylindrical acoustic lens into the sound cell between the object and the region of acousto-optic interaction and by utilizing a liquid of low acoustic velocity in the interaction region. It is convenient, particularly for systems in which live objects are being imaged, to employ water as the medium into which the objects are placed. In all previous experiments we have used water both in the object region and in the interaction region. By isolating the interaction region with a small Lucite cell and filling it with a transparent fluid of low velocity, not only will the horizontal resolution be increased but also the efficiency of the Bragg diffraction and the magnitude of the Bragg angle. An increased Bragg angle permits lower noise operation since the amount of unwanted zero-order light that spreads into the image region is diminished. The insertion of an acoustic lens can also increase the resolution but only at the expense of reducing the field of view.
Odor sensation and memory

Preface The Human Uses of Olfaction Odor Detection and Discrimination Arousal Familiarity The Persistence of Odor Odor Exposure and Odor Sensitivity Odor Processing Monitoring Odors Odor Constancy Keeping Track of Odor Quality Keeping Track of Odor Intensity Other Modalities Smells The Perception of Pollution The Psychology of Odor Perception Sources of Malodor Deodorization Fragrances and Perfumes Theories of Odor Therapy The Personal Uses of Perfume The Role of Experience Body Odors Kinship Recognition Synchronization of Menstrual Cycles Menstrual Cycle and Odor Sensitivity Odors as Aphrodisiacs The Effect of Loss of Odor Sensitivity Mother-Infant Bonding Odor Memory Limitations of Odor Memory The Special Attributes of Odor Memory The Role of Odor in Encoding Memories Loss of Odor Sensitivity The Psychology of Anosmia The Unity of Perception Diagnostic Tests Causes of Individual Differences Affected Olfactory Mechanisms Treatments The Odor Sensorium Neophobia False-Alarm Response Bias Plasticity Ecological Encoding Proactive Interference Recognition Memory An Epiphenomenal Mnemonic References Index
Insulin-induced Activation of Phosphatidylinositol (PI) 3-Kinase INSULIN-INDUCED PHOSPHORYLATION OF INSULIN RECEPTORS AND INSULIN RECEPTOR SUBSTRATE-1 DISPLACES PHOSPHORYLATED PLATELET-DERIVED GROWTH FACTOR RECEPTORS FROM BINDING SITES ON PI 3-KINASE

Phosphatidylinositol (PI) 3-kinase is an enzyme that functions in the signaling pathways downstream from multiple cell surface receptors. The p85 regulatory subunit of PI 3-kinase binds to phosphotyrosine residues of various phosphoproteins including the platelet-derived growth factor (PDGF) receptor, the insulin receptor, and insulin receptor substrate-1 (IRS-1). Using NIH-3T3 cells overexpressing the human insulin receptor, we demonstrate that the p85 regulatory subunit of PI 3-kinase binds to phosphorylated PDGF receptor in cells incubated in the absence of insulin. When insulin is added, p85 is released from phosphorylated PDGF receptors and binds to phosphorylated insulin receptors and insulin receptor substrate-1. Moreover, insulin-induced dissociation of PDGF receptors from binding sites on PI 3-kinase requires a functional insulin receptor and is not prevented by vanadate treatment. In contrast, insulin activation does not displace PDGF receptors from binding sites on Ras GTPase-activating protein. This competition for binding to PI 3-kinase provides a mechanism for cross-talk among signaling pathways initiated by distinct peptide hormones and growth factors such as insulin and PDGF.
Chemometrical Experimental Design‐Based Optimization Studies in Capillary Electrophoresis Applications

A synopsis of the authors' work detailing the use of chemometric response surface methodology (RSM) in two capillary electrophoresis (CE) studies is described. They demonstrate the usefulness of employing RSM to specific CE applications, thereby proving the utility of chemometrics design in experimental optimization.
THE REGULATION OF OXYGEN AFFINITY OF FETAL BLOOD I. IN VITRO EXPERIMENTS AND RESULTS IN NORMAL INFANTS

It has been previously shown that red cell 2,3-diphosphoglycerate (DPG) binds to reduced hemoglobin (Hb) decreasing its affinity for oxygen (O2 and that the in vitro effect of DPG on fetal Hb is less marked than on the adult Hb. The present study on whole blood provides evidence that the in vivo effect of DPG on the O2 affinity of fetal Hb is approximately 40% of that of adult Hb. It also shows that the O2 affinity of fetal blood decreases during gestation and depends on the relative proportions of adult and fetal Hb and on the level of red cell DPG.
Nickel(II) chloride catalyzed one-pot synthesis of α-aminonitriles

A simple and efficient method has been developed for the synthesis of α-aminonitriles by a onepot three- component condensation of aldehydes, amines, and potassium cyanide in acetonitrile in the presence of a catalytic amount of CoCl 2 at room temperature.
Sensory ecology, receiver biases and sexual selection

During courtship, signals are sent between the sexes, and received signals contain information that forms the basis of decision making. Much is known about signal content, but less is known about signal design-what makes signals work efficiently? A consideration of design not only gives new insights into the evolution of signals (including novelty), but also allows the development of specific and testable predictions about the direction of evolution. Recently there has been increased interest in signal design, but this has resulted in some apparently divergent views in the literature.
Decline of U.S. cancer mortality rates: expert estimates of past underreporting.

Regulatory and public health policies in the United States are predicated on the uncritical acceptance of an alleged explosion in cancer mortality rates. In reality, several studies offer evidence that cancer mortality went underreported as one goes back in time, due to progressive deficiencies in diagnostic and registration practices. Because the absence of historical records precludes a comprehensive direct verification, a group of experts were polled to estimate the impact of this bias on U.S. cancer mortality statistics. The nature of this exercise speaks against a numerical interpretation of the results; however, their broad analogic meaning suggests that age-adjusted mortality and probably the incidence of leading cancers have significantly declined for decades, with the major exception of respiratory tract cancers.
Design and performance of an all-SiC three-phase buck rectifier for high efficiency data center power supplies

This paper presents a 7.5 kW liquid cooled three-phase buck rectifier which will be used as the front-end rectifier in 400 V dc architecture data center power supply systems. SiC MOSFETs and SiC Schottky barrier diodes (SBDs) are used in parallel to obtain low power semiconductor losses. Input and output filters are designed and inductor core material is compared to reduce passive component losses. A low-loss modulation scheme and 28 kHz switching frequency are selected to optimize the converter design for efficiency. A prototype of the proposed rectifier is constructed and tested, and greater than 98.5% efficiency is obtained at full load.
SU-E-T-573: Quality and Deliverability of Intensity Modulated Neutron Radiotherapy (IMNRT) Plans

Purpose: Intensity Modulated NeutronRadiotherapy (IMNRT) has been commissioned for clinical use. The number of allowable segments in IMNRT plans is limited by MLC speed. Quality and deliverability of static IMNRT treatment plans using the TG‐119 test suite were evaluated to establish guidelines for the number of segments per plan. Methods: Treatment plans were created and optimized to specified constraints for all cases in the TG‐119 test suite using the Varian Eclipse TPS. A 4MV photon beam with similar penetration characteristics as the fast neutron beam was used as a surrogate for this optimization. Final dose calculations were performed using an in‐house TPS commissioned for neutrondose calculations. Following optimization, MLC segments were created for three ranges of total plan complexity ‐ very limited (15–23 segments), limited (24‐ 31 segments), and unlimited. Calculated DVHs were then compared for compliance with TG‐119 dose constraints. The estimated time of delivery for plans in each range was calculated based on known delivery parameters. Results: The prostate case passes all constraints for each complexity level. All other plans fail to meet at least one constraint for one or more of the complexity levels. For all cases combined, the very limited, limited, and unlimited complexity levels meet 16, 17, and 19 of 23 total dose constraints, respectively. The mean estimated delivery time for the very limited, limited, and unlimited plans is 34 minutes (range: 27–39), 40 minutes (range: 34–45), and 68 minutes (range: 53–81) respectively, neglecting any delay due to therapists entering the treatment room. Conclusion: IMNRT plan quality is limited by current MLC capabilities. IMNRT plans should be limited to 25 segments to ensure a reasonable treatment time of 45 minutes. Even with this small number of segments, we were able to meet most dose constraints set forth in TG‐119.
Neural coding during active somatosensation revealed using illusory touch

Active sensation requires the convergence of external stimuli with representations of body movements. We used mouse behavior, electrophysiology and optogenetics to dissect the temporal interactions among whisker movement, neural activity and sensation of touch. We photostimulated layer 4 activity in single barrels in a closed loop with whisking. Mimicking touch-related neural activity caused illusory perception of an object at a particular location, but scrambling the timing of the spikes over one whisking cycle (tens of milliseconds) did not abolish the illusion, indicating that knowledge of instantaneous whisker position is unnecessary for discriminating object locations. The illusions were induced only during bouts of directed whisking, when mice expected touch, and in the relevant barrel. Reducing activity biased behavior, consistent with a spike count code for object detection at a particular location. Our results show that mice integrate coding of touch with movement over timescales of a whisking bout to produce perception of active touch.
Error analysis of the finite-strip method for parabolic equations

The finite-strip method (FSM) is a hybrid technique which combines spectral and finite-element methods. Finite-element approximations are made for each mode of a finite Fourier series expansion. The Galerkin formulated method is set apart from other weighted-residual techniques by the selection of two types of basis functions, a piecewise linear interpolating function and a trigonometric function. The efficiency of the FSM is due in part to the orthogonality of the complex exponential basis: The linear system which results from the weak formulation is decoupled into several smaller systems, each of which may be solved independently. An error analysis for the FSM applied to time-dependent, parabolic partial differential equations indicates the numerical solution error is O(h2 + M−r). M represents the Fourier truncation mode number and h represents the finite-element grid mesh. The exponent r ≥ 2 increases with the exact solution smoothness in the respective dimension. This error estimate is verified computationally. Extending the result to the finite-layer method, where a two-dimensional trigonometric basis is used, the numerical solution error is O(h2 + M−r + N−q). The N and q represent the trucation mode number and degree of exact solution smoothness in the additional dimension. © 1993 John Wiley & Sons, Inc.
Dynamic simulations of the interaction between dislocations and dilute particle concentrations in metal–matrix composites (MMCs)

Abstract 3D Dislocation Dynamics (DD) simulations are presented which capture the interaction between gliding dislocations in a ductile metallic matrix and nearby dispersed spherical particles. Here the strengthening effect arises from the stress field caused by the particle-matrix mismatch, and no image stress caused by the particles is considered. A radial misfit strain of 1%, simulating thermal processing induced elastic field in aluminum matrix-silicon carbide particulate composite system, is used. Attention is limited to composites with reinforcement concentrations smaller than about 3.5% and with particle sizes smaller than about 0.8 μm. The simulations show dislocation storage in the matrix, in the form a pileup of glide loops near the particle and as part of stress relief, which in turn exerts a back stress on upcoming gliding dislocations. This manifests itself in the simulations in increased flow stress as demonstrated by the stress–strain curve. The results show increased flow stress with increased particle volume fraction as would be expected. However, flow stress is also sensitive to other microstructural features such as particle radius and the distance between the dislocations and particles, and to a lesser extent to the spatial arrangement between dislocations and particles. Overall, the calculated strengthening effect is comparable with that found in experiments.
Multifunctional composite structures for space applications

The unique combination of composite structures, SMA actuators and optical fiber sensors provides an opportunity to obtain lightweight adaptive structures for spacecraft with increased reliability and reduced payload resources. In particular, by taking advantage of the mechanical properties of certain classes of asymmetric laminated composite structures, it is possible to design and fabricate structures that possess a multitude of stable shapes. Very little energy is required to force the structure to move from one stable shape to another, and the inherent stability of the structure means that the applied energy can be removed immediately upon actuation. This conserves power and makes this class of materials uniquely adaptable to space applications, where power for actuators is at a premium. We will describe the results of a two-year program to fabricate such a structure, instrument it with optical fiber sensors, and qualify it for launch on the MightySat II.1 satellite.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Arginyltransferase Is an ATP-Independent Self-Regulating Enzyme that Forms Distinct Functional Complexes In Vivo

Posttranslational arginylation mediated by arginyl transferase (ATE1) plays an important role in cardiovascular development, cell motility, and regulation of cytoskeleton and metabolic enzymes. This protein modification was discovered decades ago, however, the arginylation reaction and the functioning of ATE1 remained poorly understood because of the lack of good biochemical models. Here, we report the development of an in vitro arginylation system, in which ATE1 function and molecular requirements can be tested using purified recombinant ATE1 isoforms supplemented with a controlled number of components. Our results show that arginylation reaction is a self-sufficient, ATP-independent process that can affect different sites in a polypeptide and that arginyl transferases form different molecular complexes in vivo, associate with components of the translation machinery, and have distinct, partially overlapping subsets of substrates, suggesting that these enzymes play different physiological functions.
Ca2+-dependent effect of acetylphosphate on spin-labeled sarcoplasmic reticulum.

Abstract Acetylphosphate produces a definite change in the spectrum of an iodoacetamide spin probe covalently bound to sarcoplasmic reticulum ATPase. The observed change, which is Ca 2+ dependent and reversible, is attributed to a protein conformational change occurring during the Ca 2+ transport cycle.
Advice from Rural Elders: What it Takes to Age in Place

Older adults prefer to age in place (AIP), and there are psychological, physiological, and economic benefits in doing so. However, it is especially challenging to AIP in rural communities. AIP models have been tested in urban settings and age-segregated communities, but they are not appropriate for rural communities. This paper presents rural AIP variables identified in the literature as well as those described by 39 older adults in five focus groups.
Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis.

Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3–18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology. MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-β cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity. MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (P⩽0.05). Prevalence of a grade of steatosis ⩾2 (P=0.05) and fibrosis (P⩽0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis ⩾2 with BMI z-score (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), β-cell secretion (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P⩽0.0001), cholesterol (P⩽0.04) and white blood cells (P=0.025); fibrosis with body weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides (P=0.05), fasting insulin (P⩽0.0001) and mean values of the hormone at the OGTT (P=0.03), HOMA-IR (P⩽0.0001)). Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.
Abstract: Adequacy of Semiparametric Approximations for Growth Models with Nonnormal Random Effects

Conventional growth models assume that the random effects describing individual trajectories are conditionally normal. In practice, this assumption may often be unrealistic. As an alternative, Nagin (2005) suggested a semiparametric group-based approach (SPGA) which approximates an unknown, continuous distribution of individual trajectories with a mixture of group trajectories. Prior simulations ( Brame, Nagin, & Wasserman, 2006 ; Nagin, 2005 ) indicated that SPGA could generate nearly-unbiased estimates of means and variances of a nonnormal distribution of individual trajectories, as functions of group-trajectory estimates. However, these studies used few random effects-usually only a random intercept. Based on the analytical relationship between SPGA and adaptive quadrature, we hypothesized that SPGA's ability to approximate (a) random effect variances/covariances and (b) effects of time-invariant predictors of growth should deteriorate as the dimensionality of the random effects distribution increases. We expected this problem to be mitigated by correlations among the random effects (highly correlated random effects functioning as fewer dimensions) and sample size (larger N supporting more groups). We tested these hypotheses via simulation, varying the number of random effects (1, 2, or 3), correlation among the random effects (0 or .6), and N (250, 500). Results indicated that, as the number of random effects increased, SPGA approximations remained acceptable for fixed effects, but became increasingly negatively biased for random effect variances. Whereas correlated random effects and larger N reduced this underestimation, correlated random effects sometimes distorted recovery of predictor effects. To illustrate this underestimation, Figure 1 depicts SPGA's approximation of the intercept variance from a three correlated random effect generating model (N 500). These results suggest SPGA approximations are inadequate for the nonnormal, high-dimensional distributions of individual trajectories often seen in practice.[Figure: see text].
Arctic Lake Physical Processes and Regimes with Implications for Winter Water Availability and Management in the National Petroleum Reserve Alaska

Lakes are dominant landforms in the National Petroleum Reserve Alaska (NPRA) as well as important social and ecological resources. Of recent importance is the management of these freshwater ecosystems because lakes deeper than maximum ice thickness provide an important and often sole source of liquid water for aquatic biota, villages, and industry during winter. To better understand seasonal and annual hydrodynamics in the context of lake morphometry, we analyzed lakes in two adjacent areas where winter water use is expected to increase in the near future because of industrial expansion. Landsat Thematic Mapper and Enhanced Thematic Mapper Plus imagery acquired between 1985 and 2007 were analyzed and compared with climate data to understand interannual variability. Measured changes in lake area extent varied by 0.6% and were significantly correlated to total precipitation in the preceding 12 months (p < 0.05). Using this relation, the modeled lake area extent from 1985 to 2007 showed no long-term trends. In addition, high-resolution aerial photography, bathymetric surveys, water-level monitoring, and lake-ice thickness measurements and growth models were used to better understand seasonal hydrodynamics, surface area-to-volume relations, winter water availability, and more permanent changes related to geomorphic change. Together, these results describe how lakes vary seasonally and annually in two critical areas of the NPRA and provide simple models to help better predict variation in lake-water supply. Our findings suggest that both overestimation and underestimation of actual available winter water volume may occur regularly, and this understanding may help better inform management strategies as future resource use expands in the NPRA.
Tear Resistance of Proton Exchange Membranes

Through the thickness flaws or “pinholes” in proton exchange membranes (PEM) allow gas crossover that can lead to fuel cell failure. The formation of these flaws is not fully understood, but one possible mechanism is that small flaws could grow through crack propagation in the fracture mechanics sense. Although relatively brittle features are sometimes observed in failures resulting under simulated fuel cell conditions, the stress strain plots of the membranes themselves exhibit considerable ductility. In an effort to use fracture mechanics principles to characterize PEMs, fracture parameters associated with the essential work of fracture from double edge notch tensile (DENT) specimens; the tear energy obtained from the trouser tear test; and cutting energies associate with knife slitting were measured and compared. Presumably through reducing crack tip blunting, the knife slitting test is able to measure fracture energies as low as 200J/m2 , two orders of magnitude smaller than measured in the other tests. The results are sensitive to rate, temperature, and moisture level. Although the implications of these properties to fuel cell durability are not yet understood, they may have applicability in the more brittle features that are sometimes observed.Copyright © 2005 by ASME
SU‐C‐105‐03: Progress Toward the Development of a Deformable Anthropomorphic 3D Dosimetric Phantom

Purpose: Previous work has demonstrated that Presage-Def, a deformable, polyurethane-based radiochromic 3D dosimeter, has strong potential for validating deformable image registration algorithms by tracking optically measured radiation patterns from the deformed shape to the non-deformed shape. Here we present recent investigations into the efficacy of variant Presage-Def formulations with a range of elastic properties in terms of increased dose sensitivity and post-irradiation stability. Methods: Eleven formulations of Presage-Def were created from combinations of 3 elastic polyurethane matrices (Shore Hardness 10–20A and 30A) and 7 leuco dyes. Dose sensitivity for each formulation was determined by irradiating cuvettes from 0–8Gy and measuring change in optical density at 633nm. Sensitivity readings were tracked over time to determine stability. Complementary to the small volume studies, a 15.7cm diameter cylindrical Presage-Def deformable dosimeter was created incorporating two air cavities (4.0cm diameter) and a rigid high-Z spine-mimic insert (2.8cm diameter). The dosimeter was subjected to bilateral compression to demonstrate complex, non-uniform deformation, and also irradiated with an 8.6cm×7.4cm field and imaged with optical-CT to investigate feasibility of optical-CT dose readout in a heterogeneous phantom. Results: Dose sensitivities ranged from 0.0004-0.0071ΔOD/(Gy*cm) versus 0.0032ΔOD/(Gy*cm) in the original formulation. Highest sensitivity and stability were both seen in formulation PD1 (#2 polyurethane, leuco dye 1-napthal-N,N-diethylamine LMG), which retained 98.6% initial sensitivity over 4 hours whereas the original dropped to 90.6% after 1 hour. X-ray CT images of the prototype phantom with and without compression demonstrated non-uniform deformation of Presage-Def and air cavity geometry while the rigid region remained constant. The irradiated field was clearly visible in 3D dose distributions obtained by optical-CT. Conclusion: A Presage-Def formulation was identified from 10 variants with improved dosimetric characteristics. Optical-CT dose readout was achieved in the prototype phantom, demonstrating feasibility of 3D dosimetry in a large deformable dosimeter containing air and rigid bone-mimic inserts. NIH R01CA100835
Electrophysiological effects of acute and chronic olanzapine and fluoxetine in the rat prefrontal cortex.

Abstract Since the prefrontal cortex (PFC) is thought to play an important role in depression and schizophrenia, we studied the effects of fluoxetine and olanzapine on PFC neurons in rats using extracellular, in vivo recordings. Acute or 5-day administration of olanzapine (1–10 mg/kg, iv or 20 mg/kg, sc) did not change the firing rate of PFC neurons. However, a 21-day treatment with olanzapine (20 mg/kg per day, sc) significantly increased the firing rate of PFC neurons and increased their responsiveness to the iontophoretic administration of the GABA A antagonist bicuculline. Acute administration of fluoxetine (10 mg/kg, iv) also did not change the firing rate of PFC neurons. However, a 21-day treatment with fluoxetine (10 mg/kg per day) significantly decreased the firing rate of PFC neurons and decreased their responsiveness to the iontophoretic administration of bicuculline. Co-administration of olanzapine (10 mg/kg per day, sc) during the last 5 days of a 21-day fluoxetine treatment (10 mg/kg per day) prevented the suppression of firing and decreased responsiveness to the iontophoretic administration of bicuculline of PFC neurons. In conclusion, chronic, but not acute, olanzapine treatment significantly enhanced the firing and excitability of PFC neurons. In addition, chronic, but not acute, fluoxetine treatment significantly suppressed the firing and excitability of PFC neurons. Further, short-term olanzapine treatment attenuated the suppression of firing and excitability of PFC neurons induced by chronic fluoxetine treatment. These effects of olanzapine, fluoxetine, and the olanzapine/fluoxetine combination in the PFC may play an important role in the beneficial therapeutic effect of these compounds in schizophrenia and depression and may have implications for the treatment of treatment-resistant depression.
Activator-Mediated Recruitment of the RNA Polymerase II Machinery Is the Predominant Mechanism for Transcriptional Activation in Yeast

Eukaryotic transcriptional activators bind to enhancer elements and stimulate the RNA polymerase II (pol II) machinery via functionally autonomous activation domains. In yeast cells, the normal requirement for an activation domain can be bypassed by artificially connecting an enhancer-bound protein to a component of the pol II machinery. This observation suggests, but does not necessarily indicate, that the physiological role of activation domains is to recruit the pol II apparatus to promoters. Here, we show that transcriptional stimulation does not occur when the activation domain is physically disconnected from the enhancer-bound protein and transferred to components of the pol II machinery. The observation that autonomous activation domains are functional when connected to enhancer-bound proteins but not to components of the pol II machinery strongly argues that recruitment is the predominant mechanism for transcriptional activation in yeast.
Lymphocyte aging in allophenic mice

Abstract Allophenic mice are chimeras which are produced from the aggregation of two genotypically distinct embryos. In this study, embryos from the C57BL/6J and A/J strains were used to produce C57BL/6J ↔ A/J allophenic mice. These strains were chosen because of their markedly different lifespans, their different glucose phosphate isomerase (GPI) isozymes, and their different H-2 haplotypes [C57BL/6J: long-lived, Gpi-1b, H-2b; A/J: short-lived, Gpi-1a, H-2a. The mice were bled at two month intervals and the composition of their peripheral blood lymphocytes determined at each point from analysis of GPI isozymes and H-2 antigens. It was founr that the proportion of long-lived (C57BL/6J) lymphocytes tended to increase with age. Moreover, the total lifespan of the allophenic mice was directly related to the percentage of long-lived lymphocytes in their peripheral blood.
Big Science and Big Data in Biology: From the International Geophysical Year through the International Biological Program to the Long Term Ecological Research (LTER) Network, 1957––Present

This paper discusses the historical connections between two large-scale undertakings that became exemplars for worldwide data-driven scientific initiatives after World War II: the International Geophysical Year (1957––1958) and the International Biological Program (1964––1974). The International Biological Program was seen by its planners as a means to promote Big Science in ecology. As the term Big Science gained currency in the 1960s, the Manhattan Project and the national space program became paradigmatic examples, but the International Geophysical Year provided scientists with an alternative model: a synoptic collection of observational data on a global scale. This new, potentially complementary model of Big Science encompassed the field practices of ecologists and suggested a model for the natural historical sciences to achieve the stature and reach of the experimental physical sciences. However, the program encountered difficulties when the institutional structures, research methodologies, and data management implied by the Big Science mode of research collided with the epistemic goals, practices, and assumptions of many ecologists. By 1974, when the program ended, many participants viewed it as a failure. However, this failed program transformed into the Long-Term Ecological Research program. Historical analysis suggests that many of the original incentives of the program (the emphasis on Big Data and the implementation of the organizational structure of Big Science in biological projects) were in fact realized by the program9s visionaries and its immediate investigators. While the program failed to follow the exact model of the International Geophysical Year, it ultimately succeeded in providing a renewed legitimacy for synoptic data collection in biology. It also helped to create a new mode of contemporary science of the Long Term Ecological Research (LTER Network), used by ecologists today.
The Rare Diseases Clinical Research Network's organization and approach to observational research and health outcomes research.

Established in 2003 by the Office of Rare Diseases Research (ORDR), in collaboration with several National Institutes of Health (NIH) Institutes/Centers, the Rare Diseases Clinical Research Network (RDCRN) consists of multiple clinical consortia conducting research in more than 200 rare diseases. The RDCRN supports longitudinal or natural history, pilot, Phase I, II, and III, case–control, cross-sectional, chart review, physician survey, bio-repository, and RDCRN Contact Registry (CR) studies. To date, there have been 24,684 participants enrolled on 120 studies from 446 sites worldwide. An additional 11,533 individuals participate in the CR. Through a central data management and coordinating center (DMCC), the RDCRN’s platform for the conduct of observational research encompasses electronic case report forms, federated databases, and an online CR for epidemiological and survey research. An ORDR-governed data repository (through dbGaP, a database for genotype and phenotype information from the National Library of Medicine) has been created. DMCC coordinates with ORDR to register and upload study data to dbGaP for data sharing with the scientific community. The platform provided by the RDCRN DMCC has supported 128 studies, six of which were successfully conducted through the online CR, with 2,352 individuals accrued and a median enrollment time of just 2 months. The RDCRN has built a powerful suite of web-based tools that provide for integration of federated and online database support that can accommodate a large number of rare diseases on a global scale. RDCRN studies have made important advances in the diagnosis and treatment of rare diseases. Electronic supplementary material The online version of this article (doi:10.1007/s11606-014-2894-x) contains supplementary material, which is available to authorized users.
The N Terminus of p53 Regulates Its Dissociation from DNA

It is important to gain insight into p53 DNA binding and how it is regulated. By using electrophoretic mobility shift assays and DNase I footprinting, we show that a region within the N terminus of the protein controls the dissociation of p53 from a p53-binding site. When p53 is bound by a number of N-terminal-specific monoclonal antibodies, its rate of dissociation from DNA is reduced, and its ability to protect a cognate site from DNase I digestion is increased. Moreover, greatly reduced dissociation is observed with p53 protein lacking the N-terminal 96 amino acids. By contrast, deletion of the C terminus does not affect p53 dissociation from DNA or DNase I protection. p53 protein expressed in and purified from bacterial cells displays markedly more instability on its consensus DNA-binding site than does p53 produced in insect cells, suggesting that post-translational modifications may affect the stability of the protein. Our results provide evidence that the N terminus of p53 possesses an auto-inhibitory function that is mechanistically different from the inhibitory region at the C terminus.
Automated detection of spiculated lesions and architectural distortions in digitized mammograms

Mammographic stellate lesions and architectural distortions are usually associated with malignancy, which makes them important signs in the screening for breast cancer. This paper proposes a novel method for the automatic detection of these lesions with the use of a Hough spectrum based geometric texture analysis. The Hough spectrum technique is developed from the traditional Hough transform, which is effective in the description of geometric structures. The Hough spectrum inherits such an ability and extends it into texture analysis for the description of those texture features geometric in nature, such as the spicula of a stellate lesion. When applied in mammographic image processing, an ROI is first transformed into its Hough spectrum, and then thresholding is conducted with its threshold level based on the statistical properties of the spectrum. Those ROIs with strong signals of spiculation are then identified as regions of potential lesions. Our preliminary studies, using only the Hough spectrum based technique without further feature analyses to reduce false positive detection, have yielded sensitivities of 81% for spiculated masses and 67% for architectural distortions at false positive rates of 0.97 and 2.2 per image, respectively. This manifests clearly the potential of the developed technique in the detection of such types of mammographic lesions.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Discussion on 'New method for rapid evaluation of spheroidisation and inoculation grade of hypereutectic cast iron'

A recent paper by Li et al. claims to have developed a new method for rapid evaluation of nodularity in cast iron based on an earlier ‘new method’ by Li consisting in combining thermal analysis with eutectic expansion. While the application of an artificial neural network may be considered to have some degree of novelty, the use of combined thermal and expansion analysis is not new and was not new when Li claimed it to be so in 1994. Indeed, the concomitant measurement of the cooling curve and solidification contraction of ductile, compacted and gray cast iron was presented as early as 1979 and even patented. Results of this earlier work obtained by combining differential thermal analysis of the cooling curve with the dimensional variation measured through an inductive displacement transducer are presented in Fig. 1. It is seen that at the beginning of cooling the transducer records an expansion because of the