cssi/SciSciGPT-SciSciNet huggingface dataset:
The mass-action law-based new computer software, CompuSyn, for automated simulation of synergism and antagonism in drug combination studies

637 Drug combination is the leading choice for treating most dreadful diseases, such as cancer and AIDS. The phrase “synergistic effect” has been cited 14,296; 7,186 and 903,000 times by PubMed, ISI and Google, respectively. Based on the unified theory of the median-effect equation of the mass-action law and the combination index theorem (Pharmacol. Rev. 58: 621-681, 2006), algorithms have been used to develop a new computer software “CompuSyn” for automated quantitative simulation of synergism or antagonism in drug combination studies, including anticancer agents, in vitro and in vivo. In this paper, we will demonstrate step-by-step, from experimental design (e.g., constant ratio and non-constant ratio combinations; simultaneous and sequential and reverse sequential combinations), to data entry, to automated simulation of synergism/antagonism, and to report generation, using specific examples of experimental data sets. This method determines the followings: 1) Whether there is a synergism? 2) If so, how much synergism? 3) Synergism at what dose levels? 4) Synergism at what effect levels? 5) How many folds of dose-reduction allowed for each drug as a result of synergism? 6) What is the optimal combination ratio for maximal synergy? and 7) What is the preferred combination schedule for better synergism? The computer generated color graphics include: 1) The dose-effect curves (including the mass-action law parametes for potency, shape and conformity statistics); 2) The median-effect plot; 3) The combination index (CI) plot for effect-oriented determination of synergism or antagonism at different effect levels; 4) The dose-reduction index (DRI) plot at different effect levels, 5) The isobologram for dose-oriented determination of synergism or antagonism, and 6) The polygonogram (for three or more drugs). The theoretical basis and utility of the above features in biomedical sciences will be demonstrated and illustrated with real examples. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation and drug discovery as well as for drug or other entity combinations with different units (e.g., µM, µg/ml, international unit), different modalities (e.g., drug, radiation, hyperthermia), and different mechanisms (e.g., against different stages of cell life-cycle, enzymes, receptors, targets, pathways, etc.). This software is published by Combosyn, Inc. (www.combosyn.com).
Novel biomanufacturing platform for large-scale and high-quality human T cells production

The adoptive transfer of human T cells or genetically-engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. The objective of this study was to develop a novel T cell biomanufacturing platform using stirred-tank bioreactor for large-scale and high-quality cellular production. First, various factors, such as bioreactor parameters, media, supplements, stimulation, seed age, and donors, were investigated. A serum-free fed-batch bioproduction process was developed to achieve 1000-fold expansion within 8 days after first stimulation and another 500-fold expansion with second stimulation. Second, this biomanufacturing process was successfully scaled up in bioreactor with dilution factor of 10, and the robustness and reproducibility of the process was confirmed by the inclusion of different donors’ T cells of various qualities. Finally, T cell quality was monitored using 12 surface markers and 3 intracellular cytokines as the critical quality assessment criteria in early, middle and late stages of cell production. In this study, a new biomanufacturing platform was created to produce reliable, reproducible, high-quality, and large-quantity (i.e. > 5 billion) human T cells in stirred-tank bioreactor. This platform is compatible with the production systems of monoclonal antibodies, vaccines, and other therapeutic cells, which provides not only the proof-of-concept but also the ready-to-use new approach of T cell expansion for clinical immune therapy.
Evaluating the Behavior and Temperament of African Penguins in a Non-Contact Animal Encounter Program

Animal ambassador programs are increasingly prevalent in zoos, yet few studies have investigated their impact on animal welfare. We assessed the effects of an ambassador program on the behavior of a colony (N = 15) of zoo-housed African penguins (Spheniscus demersus) and evaluated whether individual characteristics were predictive of participation. Behavioral data were collected for 16 weeks and included 43 “penguin encounters”, during which zoo visitors entered a designated portion of the penguins’ enclosure. When comparing colony behavior following encounters to behavior during a matched control period lacking an encounter, we found no significant difference between affiliative or aggressive behaviors, suggesting that the encounters did not disrupt interactions in the colony. The same was true when comparing behavior preceding the encounter to a matched control period, indicating that any anticipatory period was similarly non-disruptive. Space use during encounters suggested comfort near visitors. We also measured penguin temperament on the shy-bold continuum by recording the birds’ response to novel objects and found that penguins’ temperament, sex, and age were predictive of participation. We concluded that this program had a neutral or positive impact on penguin welfare and considered the findings in relation to aspects of the ambassador program that provided penguins with control over their involvement.
Arousal and the Alzheimer disease

Abstract We now turn our attention to degenerative diseases, and the first of these is the Alzheimer disease (AD). AD not only is present in many persons over 65 years of age and is progressive but also may have an early onset in the forties. Survival is on average ~ 8 years after diagnosis. Degeneration of the cortex, beginning in the temporal lobe and progressing throughout, as well as in brain stem centers, has been observed. A proportion of patients suffer from sundowning agitation, and symptoms become more severe with progression of the disease. Risk factors include genetic and environmental, head trauma, and high cholesterol. Arousal deficits suggest that there are more than one population of patients, some with decreased and some with increased arousal. Mechanisms of cell death are related to the loss of calcium homeostasis, which may involve parts of the reticular activating system and high-threshold calcium channel dysregulation. This may account for the host of arousal symptoms manifested by AD patients.
Timing and Risk Factors for Venous Thromboembolism After Rotator Cuff Repair in the 30-Day Perioperative Period.

Purpose To analyze the American College of Surgeons National Surgical Quality Improvement Program database to evaluate the incidence of deep venous thrombosis and pulmonary embolism in patients undergoing rotator cuff repair surgery. In addition, we aim to identify risk factors associated with the development of thromboembolic events following rotator cuff repair. Methods A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database was performed. Current Procedural Terminology codes were used to identify patients who underwent rotator cuff repair between 2005 and 2017. The presence of deep venous thrombosis or pulmonary embolism during the 30-day perioperative period were the primary outcomes assessed. Logistic regression analysis was performed to identify risk factors for postoperative venous thromboembolic events (VTEs). Results In total, 39,825 rotator cuff repairs (RCRs) were performed and 117 (0.3%) VTE events occurred. VTE was identified at a mean of 11.5 ± 7.4 days. A total of 31,615 RCRs were performed arthroscopically. There was no significant difference of VTE between groups comparing arthroscopic RCR VTE 0.3% (94) with open RCR 0.3% (23) (P = .81). RCR in patients with an American Society of Anesthesiologists classification of III or IV was associated with >1.5-fold increase risk of VTE (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.14-2.45). Increased risks of VTE included surgery >80 minutes (OR 2.10, 95% CI 1.42-3.15), performed under general anesthesia (OR 4.38, 95% CI 1.18-36.6), and in the outpatient setting (OR 6.09, 95% CI 1.06-243.7), male sex (OR 1.53, 95% CI 1.01-2.33), bleeding disorders (OR 2.87, 95% CI 1.17-7.05), or dyspnea (OR 1.51, 95% CI 1.02-2.23). The biggest risk for VTE was unplanned reoperation OR 16.6 (95% CI 5.13-53.5). Conclusions Venous thromboembolism is a rare complication following rotator cuff repair 0.3%. Understanding the risk factors: duration of surgery >80 minutes, male sex, body mass index >30 kg/m2, ASA III or IV, RCR as an inpatient under general anesthesia, bleeding disorder, or dyspnea may be useful in guiding treatment to prevent VTE. The largest risk for VTE is a patient with unplanned reoperation. RCR surgery performed in an outpatient setting resulted in a significantly lower incidence of VTE. Level of Evidence III Retrospective Comparative Study.
The Role of Social Isolation in the Relationships Between Psychosis and Suicidal Ideation

Social isolation relates to worse mental health outcomes, including lower quality of life, depression, and both suicidal ideation and attempt. Among individuals experiencing symptoms of psychosis, suicide is a leading cause of death and data show greater isolation relates to increased negative symptoms as compared to individuals with strong support systems. While isolation has been linked with negative symptoms in the literature, less is known about its relationships with positive symptoms of psychosis (e.g., hallucinations and delusions), particularly within the context of a general population-based sample. This study examined the relationships between hallucinations, delusions, depression, social isolation, and suicidal ideation. Participants were involved in the cross-sectional Collaborative Psychiatric Epidemiology Surveys (CPES) including a large general population-based sample of households in the United States between 2001 and 2003. Participants (n = 12,195) included adults over the age of 18 in the United States, all of whom completed a psychosis assessment. Hopelessness was measured using The Calgary Depression Scale for Schizophrenia (CDSS), hallucinations and delusions by the Positive and Negative Syndrome Scale (PANSS), and social isolation by three PANSS items (keeping to self, feeling awkward in social settings, preferring to be alone), all at baseline. Data were analyzed in Mplus 8 using structural equation modeling. As hallucinations, delusions, and depression independently increased, on average there were associated increases in social isolation and the likelihood of experiencing suicidal ideation. Social isolation also related to greater suicidal ideation and ultimately functioned as a mediator. With suicide being a leading cause of death for individuals experiencing psychosis, the mediating role of social isolation in the relationships between hallucinations, delusions, depression, and suicidal ideation speaks towards the importance of social support and skills training as important treatment targets in practice.
An Extension of Commonly Used Toilet-Training Procedures to Children with Autism Spectrum Disorder.

The current study evaluated a toilet-training treatment package described by Greer et al. (2016) with children diagnosed with autism spectrum disorder (ASD). Most of the current research on toilet-training interventions for children with ASD are replications and modifications of Azrin and Foxx (1971) or (more recently) LeBlanc et al. (2005). However, these procedures are composed of components that are not included in studies with typically developing (TD) children. For example, Greer et al. evaluated the effectiveness of three typical components within a toilet-training package, mostly with TD participants: a 30-min sit schedule, placing participants in underwear, and differential reinforcement. The primary purpose of the current study was to replicate and extend the treatment package described by Greer et al. to children with ASD. A secondary purpose was to evaluate modifications necessary for individualized toilet training when the commonly used components were ineffective. The results of Greer et al. were replicated for 11 participants with ASD in the current study, suggesting that intensive toileting interventions (e.g., interventions requiring overcorrection, reprimands, and dense sit schedules) may only be necessary for a subset of individuals with ASD.
Litter Reduction by Prescribed Burning Can Extend Downy Brome Control

Abstract Downy brome ( Bromus tectorum L.) is a highly successful invasive species primarily because it fills an open niche in native plant communities. It also produces large amounts of litter over time. We hypothesized that removing accumulated litter with a prescribed burn before applying herbicides would improve herbicide efficacy, extending the duration of control. In January 2012, two downy brome-infested sites were burned. In March 2012, postemergent applications of glyphosate, imazapic, and tebuthiuron were made in a split-plot design. Above-ground biomass was collected at 6, 18, and 27 months after treatment (MAT) to evaluate treatment effects. In nonburned areas, all herbicide treatments were similar to the control 27 MAT; however, burning combined with imazapic or tebuthiuron reduced downy brome biomass 27 MAT by 81% ± 4.6 SE and 84% ± 19.3 SE, respectively. Remnant species responded positively to burning and herbicide treatments. Native cool-season grass biomass increased after burning whereas native warm-season grass biomass increased following tebuthiuron treatments. The impact of litter on imazapic and tebuthiuron availability was also evaluated. Herbicide interception increased in a linear relationship with increasing litter. For every 50 g · m − 2 increase in litter there was a 7% increase in the amount of herbicide intercepted, meaning that 75% of the applied herbicide was intercepted by 360 g · m − 2 of litter. A simulated rainfall event of 5 mm, 7 days after application, removed a significant amount of herbicide. This indicates that in sites with surface litter, timely precipitation could be critical for herbicide efficacy; however, when burning was used to remove litter and was followed by herbicides with residual soil activity, downy brome control was extended. Due to downy brome’s relatively short seed viability in the soil, extending herbicide efficacy to several years could help to reduce the soil seed bank.
Using temperature dependent fluorescence to evaluate singlet fission pathways in tetracene single crystals

The temperature-dependent fluorescence spectrum, decay rate, and spin quantum beats are examined in single tetracene crystals to gain insight into the mechanism of singlet fission. Over the temperature range of 250 K-500 K, the vibronic lineshape of the emission indicates that the singlet exciton becomes localized at 400 K. The fission process is insensitive to this localization and exhibits Arrhenius behavior with an activation energy of 550 ± 50 cm-1. The damping rate of the triplet pair spin quantum beats in the delayed fluorescence also exhibits an Arrhenius temperature dependence with an activation energy of 165 ± 70 cm-1. All the data for T > 250 K are consistent with direct production of a spatially separated 1(T⋯T) state via a thermally activated process, analogous to spontaneous parametric downconversion of photons. For temperatures in the range of 20 K-250 K, the singlet exciton continues to undergo a rapid decay on the order of 200 ps, leaving a red-shifted emission that decays on the order of 100 ns. At very long times (≈1 µs), a delayed fluorescence component corresponding to the original S1 state can still be resolved, unlike in polycrystalline films. A kinetic analysis shows that the redshifted emission seen at lower temperatures cannot be an intermediate in the triplet production. When considered in the context of other results, our data suggest that the production of triplets in tetracene for temperatures below 250 K is a complex process that is sensitive to the presence of structural defects.
A Versatile eIF3d in Translational Control of Stress Adaptation.

Lamper et al. (2020) reported that eIF3d-mediated cap-dependent translation is subject to regulation by phosphorylation during chronic glucose deprivation, providing a mechanism underlying selective translation of stress genes essential for cell survival.
Design and Fabrication of the LA-8 Distributed Electric Propulsion VTOL Testbed

The Langley Aerodrome No. 8 (LA-8) is a distributed electric propulsion, vertical takeoff and landing (VTOL) aircraft that is being used for wind tunnel testing and free flight testing at the NASA Langley Research Center. The LA-8 test vehicle provides a low-cost, modular testbed for research in the area of Urban Air Mobility(UAM). The LA-8, a tandem tilt-wing configuration,has the potential to provide superior performance while also enabling researchinto significant areas of risksuch aseffects of winds, subsystem failures, and adequate control power and damping during transition. While all UAM VTOL designs have challenges regarding acoustics and community noise, the LA-8 vehicle can address other equally significant risks to UAM vehicle design.The LA-8 test strategy enables significant project cost reductions through the use of the exact same model for both wind-tunnel and subsequent free flight testing. Previously, wind tunnel andflight testing required separate specialized models, costing much more.The fabrication methods used on the LA-8 provide a relatively rapid and low-cost means to validate aerodynamic, acoustic, and flight dynamics analysis of new electric VTOL and short takeoff and landing (STOL) designs. In addition, the flight vehicle will be used to help develop test processes for FAA flight vehicle airworthiness certification and for the development of robust flight control algorithms that are tolerant of failures. A new approach is being used on test vehicle design that makes extensive use of 3-D printing. Although materials used in 3-D printinghave lower strength-to-weight ratios than traditional materials used for NASA’s wind tunnel and flight models, strategic placement of load-carrying structures allows the aircraft to meet structural criteria. This technique also enables rapid changes to be made in the vehicle design, such as the outer mold line, as well as easy fabrication of replacement parts. Modularity of the vehicle’s main components allows changes to the vehicle overall configuration for comparative evaluation of alternate designs. Finally, a description is given of detailed mass property measurements of the flight vehicle, including center-of-gravity (CG) location, the CG shift associated with wing tilt, and mass moments of inertia using multiple pendulum swing methods.
Assessing the Clinical Feasibility of Whole-Body Dynamic FDG PET Imaging

515 Objectives: In current standard of care (SOC) PET imaging for tumor assessment, a single timepoint of radiotracer distribution is acquired starting at ~60 minutes (min) post 18F-fluorodeoxyglucose (FDG) administration. Recently, whole-body dynamic (WBD) PET imaging has been proposed as an alternative to SOC imaging, in which short time interval whole-body PET scans (e.g. 30 sec/bed position for WBD versus 3-5 min/bed position in SOC) are obtained and repeated multiple times during an exam. The multi-pass whole body PET images can be used to model dynamic aspects of the radiotracer in addition to creation of averaged standardized-uptake value (WBD SUV) PET images similar to conventional SOC PET images. While WBD SUV images often have similar total counts to SOC imaging, there is a greater risk of motion between whole-body passes. In this study, we assessed the clinical feasibility of WBD PET imaging by comparing the image quality of PET WBD SUV images to SOC PET images. Methods: Nineteen subjects with a prior cancer diagnosis were enrolled. Each subject underwent WBD PET imaging starting at ~30 min after FDG administration on either a GE PET/CT scanner (N=8) or a GE Signa PET/MR scanner (N=11), followed by SOC PET imaging starting at ~60 min post administration on a GE PET/CT scanner. Each set of WBD SUV PET images consisted of 4-7 whole body passes which were decay corrected, averaged, and normalized to create WBD SUV images. Image quality was compared between SOC and WBD SUV PET images using a 5-point Likert scale by 2 blinded nuclear medicine physicians. Motion artifacts were also assessed as being absent, mild, or severe. Results: The SOC and WBD SUV images were scored to have either good or excellent quality, which were of diagnostic quality in all 19 cases (Table 1). Image quality was degraded in one WBD case due to significant head motion, but the motion did not impact image quality in the body (Table 2). In all other cases, WBD SUV images were scored as equivalent to SOC images in image quality (Figure 1, Example WBD SUV and SOC PET), and motion artifacts were either none or mild. Conclusions: WBD SUV PET images are comparable in image quality to SOC PET image in the body. WBD PET imaging is a promising alternative to SOC PET, yielding whole-body pharmacokinetic information in addition to high quality diagnostic PET images. Research Support: This research was supported by the UW Shapiro Medical Student Summer Research Fellowship Award and in part by a research award from GE HealthCare.
Trajectory-Free Control of Lower-Limb Exoskeletons Through Underactuated Total Energy Shaping

Kinematic control approaches for exoskeletons replicate normative joint kinematics associated with one specific task and user at a time, which makes it difficult to adjust to continuously-varying activities during gait training. These approaches also overly constrain individuals who have partial or full volitional control of their limbs, preventing these individuals from choosing their own preferred gait patterns. To address these issues, we proposed a matching framework for underactuated total energy shaping (i.e., shaping both the potential and kinetic energies) with human and environmental interaction to provide task-invariant, energetic assistance. In our prior work, we designed assistive strategies to compensate for lower-limb inertia in the actuated part of the mass matrix while leaving mass related terms unshaped. While these strategies have demonstrated potential gait benefits, shaping mass related terms in addition to lower-limb inertia can produce greater benefits as they are more dominant in determining human dynamics during locomotion. Moreover, previous definitions of closed-loop mass matrix with reduced inertial parameters cannot guarantee its positive definiteness. Having a non-positive definite mass matrix in the closed loop can render chaotic behaviors such as unbounded exoskeleton torques that cause danger to human users. In this paper, we generalize our prior work to shape all inertial terms in the actuated part of the mass matrix while ensuring its positive definiteness in the closed loop. In addition, given a positive-definite, closed-loop mass matrix, we prove passivity from human input to joint velocity and highlight two Lyapunov stability results based on common assumptions of human joint control policies. We then show benefits of the proposed approach and its advantages over conventional exoskeleton control methods with simulations on a human-like model. We also show that the corresponding assistive torques closely match the human torques of an able-bodied subject.
Synaptotagmin-7 enhances phasic dopamine release

Dopamine released from substantia nigra pars compacta (SNc) neurons modulates movement, motivation, and reward. In addition to their tonic firing pattern, dopamine neurons also fire high-frequency bursts that cause superlinear increases in dopamine release. To examine this poorly understood form of short-term plasticity, we used the fluorescent dopamine sensor dLight1.3b to examine the role of the calcium-binding protein synaptotagmin-7 (SYT7). We report that SYT7 mediates a hidden component of facilitation, which was unmasked by lowering initial release probability, or by low-frequency stimulation of nerve terminals. In Syt7 KO neurons, there was profound synaptic depression that significantly reduced release during stimulations that mimic in vivo firing patterns of SNc neurons. D2-mediated inhibitory postsynaptic currents in the SNc revealed a similar role for SYT7 in somatodendritic release. Our results indicate that SYT7 drives short-term facilitation of release from dopamine neurons, which likely underlies frequency-dependence of dopamine signaling in vivo.
Probabilistic Lexicographic Preference Trees

We introduce probabilistic lexicographic preference trees (or PrLPTs for short). We show that they offer intuitive and often compact representations of non-deterministic qualitative preferences over alternatives in multi-attribute (or, combinatorial) binary domains. We specify how a PrLPT defines the probability that a given outcome has a given rank, and the probability that a given outcome is preferred to another one, and show how to compute these probabilities in polynomial time. We also show that computing outcomes that are optimal with the probability equal to or exceeding a given threshold for some classes of PrLP-trees is in P, but for some other classes the problem is NP-hard.
Children's Understanding of Disability

Children's Understanding of Disability is a valuable addition to the debate surrounding the integration of children with special needs into ordinary schools. Taking the viewpoint of the children themselves, it explores how pupils with severe learning difficulties and their non-disabled classmates interact. Ann Lewis examines what happens when non-disabled children and pupils with severe learning difficulties work together regularly over the course of a year. She also includes the views of children working in segregated special education. From her findings, she draws implications for developing an inclusive ethos in schools and other communities.
Macular Structure and Function in Nonhuman Primate Experimental Glaucoma.

PURPOSE To evaluate structure and function of macular retinal layers in nonhuman primate (NHP) experimental glaucoma (EG). METHODS Twenty-one NHP had longitudinal imaging of macular structure by SDOCT, 16 also had recordings of function by multifocal ERG. The average thickness over 15° was derived for seven individual SDOCT layers: macular nerve fiber layer (m-NFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer+inner segments combined (ONL+IS), and outer segments (OS). Peripapillary RNFL thickness (ppRNFLT) was measured from a single circular B-scan with 12° diameter. Responses to a slow-sequence multifocal ERG (mfERG) stimulus (7F) were filtered (at 75 Hz) into low- and high-frequency components (LFC, HFC). RESULTS At final follow-up, significant structural loss occurred only in EG eyes and only for ppRNFLT (-29 ± 23%), m-NFL (-17 ± 16%), RGCL (-22 ± 15%), and IPL (-19 ± 14%); though there was also a small increase in OPL (+6 ± 7%) and ONL+IS (4 ± 4%) and a similar tendency for INL. Macular structural loss was correlated with ppRNFLT only for the NFL, RGCL and IPL (R = 0.95, 0.93 and 0.95, respectively, P < 0.0001). Significant functional loss occurred only for HFC and N2 in EG eyes. Significant longitudinal structure-function correlations (P < 0.01) were observed only in EG eyes and only for mfERG HFC and N2: HFC was correlated with ppRNFLT (R = 0.69), macular NFL (R = 0.67), RGCL (R = 0.74), and IPL (R = 0.72); N2 was correlated with RGCL (R = 0.54) and IPL (R = 0.48). High-frequency components amplitude change was inversely correlated with outer retinal thickness change (= -0.66). CONCLUSIONS Macular structural and functional losses are correlated and specific to ganglion cells over a wide range of EG severity. Outer retinal changes are likely due to inner retinal loss.
Chapter 9 Control of Rod Disk Membrane Phosphodiesterase and a Model for Visual Transduction

Publisher Summary This chapter discusses the control of rod disk membrane (RDM) phosphodiesterase (PDE) and a model for visual transduction. The transduction of single-photon absorptions into the closure of Na + channels and a change in membrane potential that serves vision in vertebrate rods have a number of characteristic properties that must be understood in terms of their underlying biochemistry and biophysics. The chapter discusses kinetic evidence from the laboratory that leads to a different model of visual transduction in which the diffusional interaction of rhodopsin with other enzymes on the surface of the RDM provides the earliest and rate-limiting steps of this process. The final stage of the model involves Ca 2+ , but all of the control of gain, speed, and sensitivity originates in the modulation of the cytoplasmic cyclic guanosine 3´,3´-monophosphate (cGMP) concentration.
CMOS VLSI design of 32/spl times/32 ATM switch using simple logic control

A 32/spl times/32 asynchronous transfer mode ATM switch consisting of interconnection network using 1/spl times/32 parallel expander circuits is presented to overcome the effect of internal path blocking. The CMOS VLSI architecture and the control unit consisting of serial shift registers and latches to keep the destination path open for the length of a packet, were designed using MAGIC software and simulated by IRSIM. The system performed well under a variety of input traffic patterns. As low as 5 ns delay was estimated by the 1/spl times/32 expander circuit, while the clock generated by the combinational circuit for latching showed a delay of 190 ns. >
Multiregion concentration diffusion coefficient determination using davidon's variable metric method

An analytic solution of the one-dimensional steadystate multiregion concentration diffusion decay equation is constructed. The solution is used to determine the diffusion coefficients of metallic fission products in high-temperature gas-cooled reactor fuel particles from experimental measurement of the concentrations using Davidon's variable metric method for chi-square minimization. Typically, for two to four material regions with 50 measured concentration data points, the diffusion coefficients and their associated uncertainties can be determined rapidly (<8 s on the AMDAHL 470/V6). Using analytical solutions, the diffusion coefficients can be determined about25 times faster than using finite difference solutions. The methodology is applied to Zoller's concentration measurements of /sup 137/Cs and /sup 90/Sr.
Genetic analysis of type-specific antigenic determinants of herpes simplex virus glycoprotein C.

Abstract Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) elicits a largely serotype-specific immune response directed against previously described determinants designated antigenic sites I and II. To more precisely define these two immunodominant antigenic regions of gC-1 and to determine whether the homologous HSV-2 glycoprotein (gC-2) has similarly situated antigenic determinants, viral recombinants containing gC chimeric genes which join site I and site II of the two serotypes were constructed. The antigenic structure of the hybrid proteins encoded by these chimeric genes was studied by using gC-1- and gC-2-specific monoclonal antibodies (MAbs) in radioimmunoprecipitation, neutralization, and flow cytometry assays. The results of these analyses showed that the reactivity patterns of the MAbs were consistent among the three assays, and on this basis, they could be categorized as recognizing type-specific epitopes within the C-terminal or N-terminal half of gC-1 or gC-2. All MAbs were able to bind to only one or the other of the two hybrid proteins, demonstrating that gC-2, like gC-1, contains at least two antigenic sites located in the two halves of the molecule and that the structures of the antigenic sites in both molecules are independent and rely on limited type-specific regions of the molecule to maintain epitope structure. To fine map amino acid residues which are recognized by site I type-specific MAbs, point mutations were introduced into site I of the gC-1 or gC-2 gene, which resulted in recombinant mutant glycoproteins containing one or several residues from the heterotypic serotype in an otherwise homotypic site I background. The recognition patterns of the MAbs for these mutant molecules demonstrated that (i) single amino acids are responsible for the type-specific nature of individual epitopes and (ii) epitopes are localized to regions of the molecule which contain both shared and unshared amino acids. Taken together, the data described herein established the existence of at least two distinct and structurally independent antigenic sites in gC-1 and gC-2 and identified subtle amino acid sequence differences which contribute to type specificity in antigenic site I of gC.
Retail clinics versus traditional primary care: Employee satisfaction guaranteed?

Purpose To examine if differences exist in the levels of autonomy and job satisfaction among primary care nurse practitioners (NPs) employed in retail clinics versus traditional primary care settings. Data sources Data were collected from 310 primary care NPs who attended the American Association of NP's 28th Annual Conference in June 2013. Participants completed a demographic form, the Misener NP Job Satisfaction Scale, and the Dempster Practice Behavior Scale. Conclusions Overall, there were no differences in job satisfaction or autonomy among NPs by practice setting. Retail NPs felt less valued and were less satisfied with social interaction, but more satisfied with benefits compared to NPs in traditional settings. NPs working in retail clinics were less likely to have intentions to leave current position compared to NPs in traditional practice settings. Implications for practice The results of this study enhance our current understanding of the linkages between levels of autonomy, job satisfaction, and practice setting among primary care NPs. The findings of this descriptive study offer valuable insights for stakeholders devoted to the development of the primary care workforce and identify modifiable factors that may influence retention and turnover rates among NPs.
The Effect of Spurious Angular Accelerations on Tracking in Dynamic Simulation

A laboratory study was conducted to investigate the effect of spurious simulator yaw motions on a pilot's control performance. A second objective was to compare the efficiency of static and dynamic simulator tracking in previously unexamined vehicle dynamics. Twelve airline pilots served as subjects in a moving-base flight simulator under congruent-motion, spurious-motion, and no-motion conditions. The results indicated a significant increase in the amount of error with increasing levels of spurious motion during the initially administered series of trials. The influence of spurious motion, however, was absent in a second series of trials. The data suggest that the pilots learned to compensate in their performance for the spurious inputs. It was also found that congruent visual and rotational cueing produced superior performance to that of tracking with visual information alone.
Can the DCoHα isozyme compensate in patients with 4a-hydroxy-tetrahydrobiopterin dehydratase/DCoH deficiency?

4a-Hydroxy-tetrahydrobiopterin dehydratase/DCoH is a bifunctional protein. In the cytoplasm it is an enzyme required for the regeneration of tetrahydrobiopterin, an essential cofactor for phenylalanine hydroxylase. In the nucleus it functions as a transcriptional coactivator by forming a 2:2 heterotetramer with the hepatic nuclear factor HNF1alpha (HNF1). Patients with a deficiency of dehydratase activity have elevated levels of phenylalanine, and accumulate 7-pterins due to degradation of its substrate 4a-hydroxy-tetrahydrobiopterin. Curiously, the hyperphenylalaninemia is transient, and no defects in the transcriptional coactivator function have been reported. Recently, a human isozyme, dehydratase/DCoHalpha, has been detected which shares 60% identity with dehydratase/DCoH. This investigation was undertaken to ascertain if dehydratase/DCoHalpha has the pre-requisite properties to compensate in individuals lacking an active form of DCoH. DCoHalpha demonstrated the ability to quantitatively alter HNF1-dependent DNA-binding in vitro whereas DCoH was ineffective in vitro. This characteristic, due to the presence of dimeric DCoHalpha, demonstrates that DCoHalpha does not require any additional mammalian regulation process to alter DNA binding and therefore, may be more effective than DCoH at low concentrations. The dehydratase activity of each isoform was measured by a direct spectrophotometric assay. Km and Vmax for DCoHalpha were both 2-3 times higher than for DCoH, thus leaving the catalytic efficiency (Vmax/Km) the same for both enzymes. In conclusion, the properties of dehydratase/DCoHalpha are consistent with the hypothesis that the activity of this isozyme could account for the relatively mild symptoms reported for patients with a defect in dehydratase/DCoH.
Olympic Mountain Goat Controversy Continues.

I have followed with great interest the continuing debate over the fate of the Olympic Mountain goats (Anunsen & Anunsen, 1993; Scheffer 1993a, 1993b; Lyman 1994). Although the authors raise some interesting points about the role of science in park management, one key element that seems to be missing in the current discussion is common sense. I feel qualified to comment on this issue because I studied the behavioral ecology of the Olympic mountain goat population for nearly five years (Hutchins 1984) and have written several of the popular articles (Hutchins & Stevens 1981; Hutchins 1986; Sleeper & Hutchins 1989) that Lyman (1994) characterizes as "part of the media blitz aimed at goat removal."
Modes of knowing: how kataphatic practice impacts our brains and behaviors

When God Talks Back is one of those rare books that not only provides “a good read,” but also good science. It is an excellent ethnography and an effective empirical examination of the proximate me...
Evaporation studies of model polar stratospheric cloud films

To investigate evaporation of polar stratospheric clouds (PSCs), mixed nitric-acid/ice films with varying HNO3 content were heated at 0.3 K min−1 in vacuum and monitored with transmission Fourier transform infrared (FTIR) spectiroscopy. The ability for HNO3 inclusions to hinder ice evaporation was found to depend on the concentration of HNO3. Specifically, films with initial compositions of ∼80:1 and ∼150:1 H2O:HNO3 evaporated ∼8 K and ∼3 K higher than pure ice, respectively. In addition, the surface coverage of nitric acid trihydrate (NAT) appears to control the overall evaporation rate. In the atmosphere, NAT may form on the surface of an ice PSC by direct HNO3 adsorption or by evaporation of a PSC with HNO3 in the bulk.
Effects of the California graduated driver licensing program

Problem: On July 1, 1998, in an effort to ameliorate the problem of high teenage driver crash rates, California implemented a graduated driver licensing system (GDLS). Method: Data on injury crashes of 16- and 17-year-old drivers from a pre-GDLS year were compared with data from two post-GDLS years. Per-capita crash rate ratios were adjusted for changes in crash rates of 25- to 34-year-old drivers, who were unaffected by the GDLS. Prevented numbers and 95% confidence intervals were estimated. Results: Fatal or severe injury crash rates were significantly lower during each of the two post-GDLS years (adjusted rate ratios (RR)=0.72 and 0.83, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Significant rate reductions were observed for all crash types, particularly for struck object (RR=0.71 and 0.80, for 2000 vs. 1997 and 2001 vs. 1997, respectively) and non-collision (RR=0.63 and 0.72, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Minor injury crash rates were also lower during post-GDLS years (RR=0.87 and 0.90, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Percent reductions were notably larger during the hours of the late night driving restriction (midnight-5 a.m.) (RR=0.79 and 0.87, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Summary: The implementation of the California GDLS was followed by large reductions in the rate of injury-producing motor-vehicle crashes. Impact on industry: This evaluation supports previous evidence that GDLS is an effective countermeasure to adolescent motor-vehicle crashes and their associated injuries. States with a traditional licensing system may prevent adolescent driver crashes by adopting a GDLS. Future studies should examine factors that influence teenager compliance with GDLS provisions and identify approaches to improving compliance.
From the Masses to the Masses

From the Masses to the Masses. An Artist in Mao's China. (Beyond the Border series.) Produced by Combat Films & Research for the David M. Kennedy Center at Brigham Young University, 2004; DVD, color, 57 minutes. Sales and distribution: http://www.beyondtheborder.org/about.php. Institutional price, US $160.00.
Extreme-value statistics for snowpack water equivalent in the northeastern United States using the cooperative observer network

Abstract A procedure is developed to estimate extreme-value statistics for snowpack water equivalent (SWE) using historical snow depth measurements at cooperative observer stations in the northeastern United States. The method specifies “pseudodensities” that allow transformation of the statistical distribution of the deepest snow-packs to the distribution of extreme SWE values at a location. These pseudodensities vary according to characteristics of the local snow climatology, the geographic location, and the values of the snow depth data themselves. The performance of a suite of theoretical probability distributions for representing the resulting distributions of extreme SWE is also investigated, and it is concluded that five-parameter Wakeby distributions provide the best representations for the region overall. The results suggest that previous estimates for extreme SWE values may underestimate the wettest snowpacks at northern and/or higher-elevation locations, but may yield overestimates in warmer po...
The pulsewave reflections model : Exploring for a fundamental mechanism of cardiovascular calcification

Cardiovascular calcification occurs in a variety of location and structure in the heart and the vasculature. Many hypotheses exist in describing local phenomena, however, there is no known global and unifying mechanism to explain all types of cardiovascular soft tissue calcification. The observed calcific changes in the cardiovascular system, however, does have a general pattern of occurring at structurally altered sites either due to disease processes or surgical manipulations. Areas of structural alterations, in conjunction with the pulsatile environment of the cardiovascular system, have been shown to disrupt normal pulsewave transmission throughout the arterial tree and induce local junctional or interfacial stress gradients. As such, these induced stress gradients can potentially aggregate and deposit cellular products and ionic particles at local sites to initiate calcification. A fundamental mechanism influencing all cardiovascular calcification is proposed based on pathophysiologic pulsewave propagations and reflections at these sites of structural changes. Initial supporting results of the theoretical model and experimentations are discussed leading to a call for future research in this direction.
Collaborative Traffic-Aware Intrusion Monitoring in Multi-channel Mesh Networks

Intrusion monitoring is an indispensable security measure for multi-channel wireless mesh networks. This paper studies how to use mesh routers to monitor a network while supporting regular traffic. This paper shows that the traffic aware monitoring (TRAM) problem is an NP-hard problem, which is challenging in coordinating monitoring and traffic forwarding to provide maximal monitoring coverage. This paper proposes three heuristic strategies for seeking optimal monitoring channels and develops a TRAM protocol for accommodating monitoring and transmission simultaneously in mesh networks. The evaluation shows that the proposed TRAM scheme can effectively utilize mesh routers' idle time for monitoring with only minor impact to regular traffic.
A Comparison of the Spontaneous Writing Quotient of the Test of Written Language (3rd ed.) and Teacher Ratings of Writing Progress

The third edition of the Test of Written Language (TOWL-3; Hammill & Larsen, 1996) is among the most commonly used writing assessment instruments, but research on this tool is somewhat limited. Giv...
Technology: Inventing beauty

Robert P. Crease revels in the life of a Hollywood goddess who pioneered wireless technology.
Generalization of the quantized Bogoliubov-Valatin transformation and relation to the method of the vector coherent state: The case of U(3)

Abstract The idea of vector coherent state has been applied recently to the problem of deriving matrix representations of Lie algebras. Central to the application of this concept is a mapping onto a space that is the direct product of a collective (boson) space and of an intrinsic space. In this paper, it is suggested that for applications to nuclear physics, a natural realization of the intrinsic space is in terms of quasifermions that are required to be kinematically independent of the bosons. This requirement leads to operator constraints that modify the anticommutation relations of the quasifermions, but otherwise leave their algebraic relations indistinguishable from those of ordinary fermions. The various concepts as well as the relations among them are illustrated by a nuclear model with the symmetry of the unitary algebra U(n). Full calculations are carried through only for n = 3 by an algebraic method, that we have also utilized previously. For the mapping of the group generators, this technique is fully equivalent to the direct use of the vector coherent state. Here it is applied as well to the problem of mapping individual fermion operators, which is a major step toward obtaining the matrices of all shell-model tensors, reduced with respect to the collective algebra. Such a mapping of fermion operators first appeared in the literature for the case of SU(2), where it is known as the quantized Bogoliubov-Valatin transformation.