cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure-based protein NMR assignments using native structural ensembles

An important step in NMR protein structure determination is the assignment of resonances and NOEs to corresponding nuclei. Structure-based assignment (SBA) uses a model structure (“template”) for the target protein to expedite this process. Nuclear vector replacement (NVR) is an SBA framework that combines multiple sources of NMR data (chemical shifts, RDCs, sparse NOEs, amide exchange rates, TOCSY) and has high accuracy when the template is close to the target protein’s structure (less than 2 A backbone RMSD). However, a close template may not always be available. We extend the circle of convergence of NVR for distant templates by using an ensemble of structures. This ensemble corresponds to the low-frequency perturbations of the given template and is obtained using normal mode analysis (NMA). Our algorithm assigns resonances and sparse NOEs using each of the structures in the ensemble separately, and aggregates the results using a voting scheme based on maximum bipartite matching. Experimental results on human ubiquitin, using four distant template structures show an increase in the assignment accuracy. Our algorithm also improves the robustness of NVR with respect to structural noise. We provide a confidence measure for each assignment using the percentage of the structures that agree on that assignment. We use this measure to assign a subset of the peaks with even higher accuracy. We further validate our algorithm on data for two additional proteins with NVR. We then show the general applicability of our approach by applying our NMA ensemble-based voting scheme to another SBA tool, MARS. For three test proteins with corresponding templates, including the 370-residue maltose binding protein, we increase the number of reliable assignments made by MARS. Finally, we show that our voting scheme is sound and optimal, by proving that it is a maximum likelihood estimator of the correct assignments.
Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: Implications for disease pathogenesis

The notion that microvascular abnormalities contribute to deleterious changes in the Alzheimer's disease (AD) brain is supported by work from our laboratory and others demonstrating biochemical and functional alterations of the microcirculation in AD. The objective of this study is to determine whether levels of neurotoxic (thrombin) and inflammatory (interleukin 8 (IL-8), integrins alphaVbeta3 and alphaVbeta5) proteins are altered in microvessels isolated from AD patients compared to levels in vessels obtained from non-demented age-matched controls. We also evaluate in AD and control microvessels expression of the transcription factor hypoxia-inducible factor 1-alpha(HIF1-alpha), which regulates pro-inflammatory gene expression, and the regulation of HIF1-alpha expression by thrombin in cultured brain endothelial cells. Our results indicate that in AD there are high levels of expression of the neurotoxic protease thrombin and the inflammation-associated proteins IL-8 and alphaVbeta3 and alphaVbeta5 integrins. HIF1-alpha is higher in AD microvessels compared to control and thrombin treatment of cultured brain endothelial cells results in increased expression of HIF1-alpha. These data suggest that in AD the cerebral microcirculation is a source of neurotoxic and inflammatory mediators and as such contributory to pathologic processes ongoing in the AD brain.
Strategies for Success in the Acute Care Nurse Practitioner Role

This article reviews issues related to development of the role of the acute care nurse practitioner (ACNP). Strategies for ensuring success in the role are outlined, including the importance of communication about the role, maintaining competency, forming collaborative relationships, and the value of networking. The ACNP represents an innovative role in advanced practice nursing. Demonstrating the outcomes of ACNP practice ensures recognition of the impact and value of this unique role.
Politics and the Limits of a Science of Governance: Some Reflections on the Thought of Bernard Crick

This paper examines Bernard Crick’s ideas on the nature of politics and explores their implications for a scientific approach to governance like that advocated recently by public management writers. It is argued here that such an approach generally downplays the inherently political character of governance because it ignores the conflicts of values and the uncertainty that are an inherent part of the way in which we have come to govern ourselves.
Enhanced-efficiency, narrow-band gigawatt microwave output of the reditron oscillator

Experiments are described which confirm theoretical predictions of higher-efficiency, narrower-bandwidth microwave output of the reditron oscillator over simple vircator high-power microwave devices. The authors produced 1.6 GW of microwave power at 2.46 GHz. The conversion efficiency from beam power to microwave power was 5.5 to 6%, exceeding the usual 1 to 3% efficiency obtained with conventional vircators. The 1% bandwidth was about a factor of 10 less than the usual value for virtual cathode oscillators. Results of computer calculations in reasonable agreement with the experimental findings are presented. >
Activities of Dicationic Compounds against Trichomonas vaginalis

We evaluated 44 novel cationic compounds for activity against metronidazole-sensitive and -resistant Trichomonas vaginalis isolates. Six compounds in three different structural classes demonstrated 50% inhibitory concentrations as low as 1 microM against both sensitive and resistant isolates, suggesting a mode of action independent of parasite biochemical pathways that confer resistance to 5-nitroimidazoles.
Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity

Novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is presented, along with successful efforts to diminish EGFR activity present in the lead series.
Learning Places from Views: Variation in Scene Processing as a Function of Experience and Navigational Ability

Humans and animals use information obtained from different viewpoints to form representations of the spatial structure of the world. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the neural basis of this learning process and to show how the concomitant representations vary across individuals as a function of navigational ability. In particular, we examined the effect of repeating viewpoint and/ or place information over both short (within-trial) and long (across-scan) intervals on the neural response in scene processing regions. Short-term fMRI adaptation effects in the parahippocampal cortex were initially highly viewpoint-specific but became less so over time. Long-term fMRI repetition effects included a significant viewpoint-invariant component. When individual differences in navigational ability were considered, a significant correlation between the strength of these effects and self-reported navigational competence was observed. In particular, good navigators encoded representations that differed between new and old views and new and old places, whereas bad navigators did not. These results suggest that cortical scene representations evolve over time to become more viewpoint-invariant and that the quality of these representations directly impacts navigational ability.
After-Hours Radiology: Challenges and Strategies for the Radiologist.

OBJECTIVE. Because of the increase in the use of 24-hour-a-day 7-day-a-week real-time radiologic interpretation, radiologists more frequently perform after-hours work. The purpose of this article was to examine the challenges arising from after-hours work and describe evidence-based strategies meant to limit the adverse physical and psychologic stresses of after-hours work. CONCLUSION. Working nontraditional hours affects a radiologist's health, social life, professional productivity, and possibly interpretive accuracy. Appropriate attention to these factors and targeted countermeasures can optimize the professional development and personal well-being of radiologists working after hours.
Parametric Probability Distributions

Abstract Parametric distributions are theoretical mathematical forms, which are often useful for compactly representing variations and uncertainty in data. Different classes of these distributions are appropriate for discrete and continuous data. These characterizations can provide the mathematical structure for inferences about the data-generating processes. Generation of random numbers from these distributions provides the basis for statistical simulation.
Berkshire Hathaway: The Role of Trust in Governance

Despite being one of the largest corporations in the world, Berkshire Hathaway receives relatively little public attention for its management and governance structure. Berkshire Hathaway is built on a model that involves extreme centralization of capital allocation decisions within corporate headquarters and extreme decentralization of operating decisions within individual business units.While many public corporations implement strict controls and oversight mechanisms to ensure management performance and regulatory compliance, Berkshire has moved in the opposite direction. Managers receive practically no supervision for their actions and are given complete autonomy to run their businesses.We explore how this system works and why it is an important exception to the best practices advocated by governance experts.Topics, Issues and Controversies in Corporate Governance and Leadership: The Closer Look series is a collection of short case studies through which we explore topics, issues, and controversies in corporate governance. In each study, we take a targeted look at a specific issue that is relevant to the current debate on governance and explain why it is so important. Larcker and Tayan are co-authors of the book Corporate Governance Matters, and A Real Look at Real World Corporate Governance.Related Teaching Case ($): The Management of Berkshire Hathaway; Case Number: CG-16; Publication Year: 2009 (SSRN), available at: http://ssrn.com/abstract=1482085.
Optical and electrical diagnostics on extended Dielectric Barrier Discharge source

The DBD (Dielectric Barrier Discharge) is well known for its great advantages in various kinds of industrial applications and has been widely used in manufacturing process including flat panel displays, thin films and semiconductor packaging. There has been enormous progress on DBD source development and diagnostics to suit these different purposes. At the same time, there are increasing needs for moderate and efficient remote plasma sources in order to avoid electrical damage from microarcs or high energy ion collisions. To this end, a stable remote plasma using an extended DBD source having a stable effective discharge area of 550mm × 40mm was investigated. The electron temperature was measured from a Boltzmann plot based a PLTE (Partial Local Thermodynamic Equilibrium) model and electron density measured from linewidth broadening of H β line, with hydrogen insertion for comparison of the direct discharge region in between electrodes and the remote plasma region. The capacitance of DBD electrode as well as discharge energy and discharge power has been investigated with V-Q Lissajous analysis. Surface treatment of glass and polypropylene with various applied voltage and gas flow rates were studied. Combining optical and electrical diagnostics and surface analysis results on treated samples, the atmospheric plasma source for in-line processing was characterized.
Postoperative Spine Infections: Prevention and Treatment

Several patient-related risk factors for postoperative spine infections exist. Those modifiable risk factors, such as malnutrition and glucose control, should be optimized before surgery with the hopes of lessening any associated infection risk. Furthermore, other operative variables, such as antibiotic administration, should also be closely monitored. However, postoperative infections always remain inevitable. Prompt diagnosis and proper treatment is the key to reduce any associated morbidity for the patient. The tenants of treatments remain surgical debridement with and without implant removal, and antibiotic therapy.
Neurometabolic roles of ApoE and Ldl-R in mouse brain

Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer's disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life.
Juvenile Hormone Analogues Tested On Larvae of Western Spruce Budworm

Four analogues of insect juvenile hormone were tested for effects on 6th instars of Choristoneura occidentalis Freeman. These were Law’s juvenile hormone mixture; 10,11-epoxymethylfarnesenate; 3-ethyl-7-methyl-6-epoxy-2-nonene-1-oxy (3,4-methylenedioxy benzene), and 3,7-dimethyl-6-epoxy-2-octen-1-oxy (3,4-methylenedioxy benzene). The purpose was to observe effects of these chemicals on fecundity, metamorphosis, and survival. At low dosages, the compounds tended primarily to decrease egg production and hatch. Higher dosages resulted in increasing degrees of morphogenetic juvenilization. Some of the more potent compounds caused supernumerary molts.
Cardiogenic shock after acute myocardial infarction: Incidence and Mortality from a Community-Wide Perspective, 1975 to 1988

Abstract Background. Cardiogenic shock resulting from acute myocardial infarction is a serious complication with a high mortality rate, but little is known about whether its incidence or outcome has changed over time. As part of an ongoing population-based study of acute myocardial infarction, we examined trends over time in the incidence and mortality rate of cardiogenic shock after acute myocardial infarction. Methods. We studied 4762 patients with acute myocardial infarction who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area between 1975 and 1988. We determined the incidence of and short-term and long-term mortality due to cardiogenic shock in each of six years during this study period. Results. The incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant, averaging 7.5 percent. Multivariate regression analysis that controlled for variables affecting incidence revealed significant though inconsistent temporal trends in the in...
The application value of 16-slices Spiral CT in the diagnosis of urological system disease

Objective To detect the diagnostic value of 16-slices Spiral CT in the diseases of urological system. Methods 115 cases with urological system disease were performed CT scanning by 16-slices Spiral CT. There are 60 cases were performed only for 16-slices plain spiral scan and 51 cases for 4-phases scan (palin scan, cortex phase, parenchymal phase and pelvis phase). Within the 51cases, 30 were performed by Sure-Start software and the other 21 cases were performed conventional enhancement scan. Non-enhancement urography is 4 cases. Within the 115 cases, there were 17 cases of congenital malformation, 2 cases of walnut cramp sign, 10 cases of urologic tuberculosis, 3 cases of polycystic kidney, 10 cases of pure kidney cysts, 58 cases of urologic stone and 15 cases of urologic tumor. All the dates were sent to the workstation for 3D post processing and the whole urogram, including therenal calices, renal pelvis, nephric duct and bladder were acquired. Results The 16-slices Spiral CT can display the anatomic structure of the urological system and the renal function, as well as the spatial relation between the pathological changes and the urinary passage. Conclusion 16-slices Spiral CT can display the location of the urological system diseases and diagnose their characters and evaluate the degree of the urinary obstruction and renal function. It can also provide the whole urogram. Therefore, it can supply more detailed and accurate evidence for the clinic.
Social Determinants of Health and Primary Care: Intentionality Is Key to the Data We Collect and the Interventions We Pursue

Social determinants of health (SDOHs)—the conditions where we live, learn, work, and play—often influence the lives of patients much more than health care services. Family physicians in particular witness the impact of these factors on a daily basis in clinical practice, and they have begun to screen for SDOHs and intervene when appropriate to mitigate their effects. This issue of the Journal of the American Board of Family Medicine focuses on SDOH data collection and analysis that informs patient care, population health, and policy interventions. Collectively, this series of articles establishes the foundation for a robust SDOH research agenda for primary care.
Recent Research Projects by the FDA’s Pharmacology and Toxicology Statistics Team

In addition to regular review work, the Pharmacology and Toxicology Statistics Team in CDER/FDA is actively engaged in a number of research projects. In this chapter we summarize some of our recent investigations and findings.
Introduction to the Perinatal-20 treatment research demonstration program.

During the 1980s sufficient evidence accumulated to suggest that the use of cocaine and other illegal drugs by pregnant women presented a major public health problem (Frank et al. 1988; Neerhof et al. 1989). Prenatal alcohol and other drug abuse was occurring in all racial and ethnic groups and across all social strata. For example, the results of a study conducted in 1989 in Pinellas County, Florida, found that positive toxicology for illegal drugs varied little between women admitted to public health clinics for prenatal care and women seen in several private obstetric practices (Chasnoff et al. 1990).
I. Visions of epithelial research

Epithelial cells are gatekeepers that sit at the interface between two compartments. By controlling the flow of molecules and information between two compartments, epithelial cells provide unique benefit to the body. This article provides a brief appraisal of our current knowledge about the functions of gastrointestinal epithelial cells as a functionally diverse set of cells mediating transepithelial transport and as a continually renewing layer of cells. The convergence of new methodologies in laser capture microdissection, microarray analyses, microscopic analyses, and generation of mutant animals provides an exciting template for future research.
Burn Care on Cruise Ships-Epidemiology, international regulations, risk situation, disaster management and qualification of the ship's doctor.

With the increasing numbers of passengers and crew on board vessels that are becoming larger and larger, the demand for ship's doctors who can adequately treat burns on board has also increased. In the cruise ship industry it is usually those doctor's with internal and general medical training who are recruited from an epidemiological point of view. Training content or recommendations for the treatment of thermal lesions with the limited options available in ship's hospitals and where doctors with no surgical training operate do not yet exist. The guidelines recommended by the Cruise Lines International Association (CLIA) regarding medical staff have only included physicians with minor surgical skills until now. With the introduction of the ATLS(®) course developed by the American College of Surgeons, the requirements for the qualification of the ship's doctor on board cruise ships shall change from January 2017. The article discusses the question of whether having completed the ATLS(®) course, the ship's doctor is trained to adequately treat thermal lesions or severe burns persons on-board, and presents the current discussion on the training content for ship's doctors within the International Maritime Health Association (IMHA). It also provides an overview of existing international regulatory frameworks, the risks presented by a fire on board, the problem of treating burns victims out of reach of coastal rescue services, and alternative training concepts for ship's doctors regarding the therapy of thermal lesions on-board.Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved. Language: en
Fate of Listeria monocytogenes in Sweetened Condensed and Evaporated Milk During Storage at 7 or 21 °C.

Sweetened condensed and evaporated milks were inoculated to contain ca. 103 to 107 cells of Listeria monocytogenes (strains Scott A, California, or V7)/ml. Both inoculated products were cooled from 25°C to 21°C in ca. 2 h or to 7°C in ca. 4 h. When inoculated sweetened condensed milk was held at 7°C for 42 d, there was no appreciable decrease in numbers of L. monocytogenes strains Scott A and V7, whereas the population of L. monocytogenes strain California decreased by ca. 1.2 orders of magnitude. Inoculum level had no effect on the magnitude of the decrease. At 21°C, 42 d of storage resulted in a more pronounced decrease in numbers of L. monocytogenes than it did during storage at 7°C, with numbers of the pathogen decreasing by 1.7, 1.6, and 3.4 orders of magnitude for strains Scott A, V7, and California, respectively. All strains of L. monocytogenes not only survived but grew in evaporated milk stored at 7 or 21 °C for 56 or 28 d, respectively.
Fermentation of eastern gamagrass (Tripsacum dactyloides [L.] L.) by mixed cultures of ruminal microorganisms with or without supplemental corn.

Five dual-flow fermentors (700 mL) were used to determine the effects of eastern gamagrass (Tripsacum dactyloides [L.] L.) diets on microbial metabolism by mixed rumen cultures. Fermentors were incubated with filtered ruminal contents and allowed to adapt for 4 d to diets followed by 3 d of sample collection. Five dietary treatments were tested: 1) gamagrass hay (GH) + no corn (GHNC), 2) gama grass silage (GS) + no corn (GSNC), 3) GS + low corn (GSLC), 4) GS + medium corn (GSMC); and 5) GS + high corn (GSHC). The experiment was conducted as a randomized complete block design with five treatments and three replications. Total VFA concentrations were not affected by diets. Corn addition linearly decreased (P < 0.001) molar proportion of acetate. In contrast, molar proportion of propionate was reduced in GSLC (cubic effect, P < 0.001) but remained similar across other diets. Corn supplementation linearly increased molar proportion of butyrate (P < 0.001). The acetate + butyrate-to-propionate ratio was highest in cultures offered GSLC (cubic effect, P < 0.001) but similar across other diets. Feeding GSNC resulted in a higher ruminal pH compared with GHNC (P < 0.03). Increasing the level of corn supplementation in GS linearly decreased culture pH (P < 0.001). All diets resulted in similar methane production, with the exception of GSMC, which lowered methane output (quadratic effect, P < 0.004). Total substrate fermented to VFA and gas tended to be greater with GHNC than with GSNC (P < 0.06) and linearly increased with the addition of corn (P < 0.004). Neutral detergent fiber digestibility was similar between GH and GS and was not affected by supplemental corn. Microbial N flow increased in cultures offered GSHC (quadratic effect, P < 0.02). Corn supplementation at the medium and high level linearly decreased C 18:0 (P < 0.02) and increased trans-C 18:1 (P < 0.004). Including corn at the high level with GS did not have a detrimental effect on fermentation in dual-flow fermentors.
Halide-regulated growth of electrocatalytic metal nanoparticles directly onto a carbon paper electrode

Direct growth of hierarchical micro/nanostructured metal arrays on a 3D substrate is a powerful tool to enhance the catalytic efficiency of metal particles towards a wide range of substrates. In this contribution, we demonstrate a novel and versatile method for growing anisotropic microstructures directly onto a 3D carbon paper electrode, using Au, Pd and Pt nanoparticles as elementary building blocks. It was determined that halides play a crucial role in the morphology of synthesized Au particles, leading to either complex flower-like rough surfaces (exhibiting high catalytic activity) or featureless smooth surfaces (exhibiting low catalytic activity). Of the three metal materials studied, the Pt decorated carbon paper (Pt@carbon) material exhibits a high electrocatalytic activity toward the oxygen reduction reaction in an alkaline medium. We demonstrate that this new Pt material can operate as a cathode in an alkaline glucose fuel cell exhibiting outstanding peak power density of 2–3 mW cm−2 (using an anode of Au@carbon or Pt@carbon at room temperature and low metal loading without any fuel circulation). This newly described fabrication approach allows for the rational control of metallic particle growth, paving a new way towards materials with regulated surface roughness allowing for tuneable physical, optical and catalytic properties.
A novel nonpharmacological intervention – breathing-controlled electrical stimulation for neuropathic pain management after spinal cord injury – a preliminary study

OBJECTIVE The objective of this study was to examine the effectiveness of a novel nonpharmacological intervention - breathing-controlled electrical stimulation (BreEStim) - for neuropathic pain management in spinal cord injury (SCI) patients. SUBJECTS AND METHODS There were two experiments: 1) to compare the effectiveness between BreEStim and conventional electrical stimulation (EStim) in Experiment (Exp) 1 and 2) to examine the dose-response effect of BreEStim in Exp 2. In Exp 1, 13 SCI subjects (6 males and 7 females, history of SCI: 58.2 months, from 7 to 150 months, impairments ranging from C4 AIS B to L1 AIS B) received both BreEStim and EStim in a randomized order with at least 3 days apart. A total of 120 electrical stimuli to the median nerve transcutaneously were triggered by voluntary inhalation during BreEStim or were randomly delivered during EStim. In Exp 2, a subset of 7 subjects received BreEStim120 and 240 stimuli randomly on two different days with 7 days apart (BreEStim120 vs BreEStim240). The primary outcome variable was the visual analog scale (VAS) score. RESULTS In Exp 1, both BreEStim and EStim showed significant analgesic effects. Reduction in VAS score was significantly greater after BreEStim (2.6±0.3) than after EStim (0.8±0.3) (P<0.001). The duration of analgesic effect was significantly longer after BreEStim (14.2±6 hours) than after EStim (1.9±1 hours) (P=0.04). In Exp 2, BreEStim120 and BreEStim240 had similar degree and duration of analgesic effects. CONCLUSION The findings from this preliminary study suggest that BreEStim is an effective alternative nonpharmacological treatment for chronic neuropathic pain in patients suffering from SCI.
Three-terminal cell for thin film dielectric measurements

A cell has been designed and built for measurement of the dielectric constant and dissipation factor of thin films. The principle employed is the two-fluid, three-terminal scheme, 1,2, 3 adapted to thin film measurements. Measurements of dielectric constant, dissipation factor and thickness can be obtained on films ranging from about 250 μm (10 mil) down to 1 μm (0. 04 mil). Agreement is in general better than 1%, except for the dissipation factor of very low loss films where bridge sensitivity is the limiting factor.
Cancer prevention in the era of precision oncology.

Cancer is a highly heterogeneous disease, both between and within different target organs. Precision cancer prevention requires understanding the molecular pathways leading to cancer on a “per-person” level, identification of individuals most at risk for developing cancer, and tailoring interventions to accommodate pathogenesis, risk, and individual responses to interventions. This commentary will discuss how an investment in precision prevention research can accelerate cancer prevention agent development—the key to reducing cancer incidence and mortality.
Nonequilibrium Chemical Effects in Single-Molecule SERS Revealed by Ab Initio Molecular Dynamics Simulations

Recent developments in nanophotonics have paved the way for achieving significant advances in the realm of single-molecule chemical detection, imaging, and dynamics. In particular, surface-enhanced Raman scattering (SERS) is a powerful analytical technique that is now routinely used to identify the chemical identity of single molecules. Understanding how nanoscale physical and chemical processes affect single-molecule SERS spectra and selection rules is a challenging task and is still actively debated. Herein, we explore underappreciated chemical phenomena in ultrasensitive SERS. We observe a fluctuating excited electronic state manifold, governed by the conformational dynamics of a molecule (4,4′-dimercaptostilbene, DMS) interacting with a metallic cluster (Ag20). This affects our simulated single-molecule SERS spectra; the time trajectories of a molecule interacting with its unique local environment dictates the relative intensities of the observable Raman-active vibrational states. Ab initio molecular ...
The Simulation-Based Assessment of Pediatric Rapid Response Teams.

Objective To create scenarios of simulated decompensating pediatric patients to train pediatric rapid response teams (RRTs) and to determine whether the scenario scores provide a valid assessment of RRT performance with the hypothesis that RRTs led by intensivists-in-training would be better prepared to manage the scenarios than teams led by nurse practitioners. Study design A set of 10 simulated scenarios was designed for the training and assessment of pediatric RRTs. Pediatric RRTs, comprising a pediatric intensive care unit (PICU) registered nurse and respiratory therapist, led by a PICU intensivist-in-training or a pediatric nurse practitioner, managed 7 simulated acutely decompensating patients. Two raters evaluated the scenario performances and psychometric analyses of the scenarios were performed. Results The teams readily managed scenarios such as supraventricular tachycardia and opioid overdose but had difficulty with more complicated scenarios such as aortic coarctation or head injury. The management of any particular scenario was reasonably predictive of overall team performance. The teams led by the PICU intensivists-in-training outperformed the teams led by the pediatric nurse practitioners. Conclusions Simulation provides a method for RRTs to develop decision-making skills in managing decompensating pediatric patients. The multiple scenario assessment provided a moderately reliable team score. The greater scores achieved by PICU intensivist-in-training-led teams provides some evidence to support the validity of the assessment.
A novel dense granule protein, GRA41, regulates timing of egress and calcium sensitivity in Toxoplasma gondii.

Summary Toxoplasma gondii is an obligate intracellular apicomplexan parasite with high seroprevalence in humans. Repeated lytic cycles of invasion, replication and egress drive both the propagation and the virulence of this parasite. Key steps in this cycle, including invasion and egress, depend on tightly regulated calcium fluxes and, while many of the calcium-dependent effectors have been identified, the factors that detect and regulate the calcium fluxes are mostly unknown. To address this knowledge gap, we used a forward genetic approach to isolate mutants resistant to extracellular exposure to the calcium ionophore A23187. Through whole genome sequencing and complementation we have determined that a nonsense mutation in a previously uncharacterized protein is responsible for the ionophore resistance of one of the mutants. The complete loss of this protein recapitulates the resistance phenotype and importantly shows defects in calcium regulation and in the timing of egress. The affected protein, GRA41, localizes to the dense granules and is secreted into the parasitophorous vacuole where it associates with the tubulovesicular network (TVN). Our findings support a connection between the TVN and ion homeostasis within the parasite, and thus a novel role for the vacuole of this important pathogen.
Silicon Composite Electrodes with Dynamic Ionic Bonding

Silicon (Si) composite electrodes are developed with increased cycle lifetimes and reliability through dynamic ionic bonding between active Si nanoparticles and a polymer binder. Amine groups are covalently attached to Si nanoparticles via surface functionalization. Si composite electrodes are fabricated by combining the Si nanoparticles with a poly(acrylic acid) (PAA) binder. The formation of ionic bonds between amine groups on Si particles and carboxylic acid groups on the PAA binder is characterized by X-ray photoelectron spectroscopy and Raman spectroscopy. Si composite anodes with ionic bonding demonstrate long term cycling stability with capacity retention of 80% at 400 cycles at a current density of 2.1 A g−1 and good rate capability. The dynamic ionic bonds effectively mitigate the deterioration of electrical interfaces in the composite anodes as suggested by stable impedance over 300 cycles.
A Systems Approach to Altered States of Consciousness

In more than 15 years of observing and researching the phenomena termed altered states of consciousness, I have been repeatedly impressed with the incredible range of phenomena encompassed by that term and with the high degree of unrelatedness of most of these phenomena. Hundreds of people have given me reports of radical alterations in the functioning of their consciousness, not only about such relatively familiar things as the changes caused by sleep and dreaming or by strong emotional states, but about changes associated with more exotic techniques, like various meditations, hypnosis, marijuana intoxication, intoxication with major psychedelic drugs, mediumistic trance states, out-of-the-body experiences, a variety of idiosyncratic states that seem to be unique to given persons, states that seem to be socially shared by groups of practitioners of particular spiritual disciplines, and experiences of that category that we vaguely label mystical experiences.
Clustering: Spatial Autocorrelation and Location Quotients

Geographic concentration of employment types frequently yields clusters exhibiting moderate-to-strong positive spatial autocorrelation. Such clusters based upon geographic proximity, and frequently quantified with location quotients, also can relate to local indices of spatial autocorrelation, such as LISA and the Getis-Ord statistics. Carroll et al. (Ann Reg Sci 42:449–463, 2008) furnish a comparison of these sets of indices. This chapter adds to that literature, but by conceptualizing location quotients as spatially autocorrelated binomial random variables.
Treatment-refractory anti-MOG antibody encephalomyelitis in an adult man (P1.090)

Objective: Myelin oligodendrocyte glycoprotein (MOG) is exclusively found on the surface of oligodendrocytes. Anti-MOG antibody causes inflammatory demyelination, with a spectrum of bilateral or recurrent optic neuritis, ADEM, and longitudinally extensive transverse myelitis. We describe treatment-refractory anti-MOG antibody-associated encephalomyelitis. Background: A 47-year-old gentleman developed difficulty urinating, arm paresthesia, and loss of hand dexterity. IV methylprednisolone caused moderate improvement, but symptoms recurred when steroids were tapered. Two months later became weak, unable to walk, and was intubated for acute respiratory failure from an expanding longitudinally extensive cervical cord lesion. He was treated with plasma exchange, mycophenolate mofetil and rituximab for presumed seronegative NMO. Three months later the patient developed diplopia, blurred vision, left facial droop, slurred speech, somnolence and confusion. MRI revealed a new enhancing lesion in the right pontocerebellum, diffuse cervicomedullary and thoracic cord enhancement, cranial nerve enhancement, and unilateral optic neuritis. Serum was positive for anti-MOG antibodies; negative for aquaporin-4 antibodies. Methylprednisolone and plasma exchange led to mild neurologic improvement. Brain biopsy revealed extensive white matter macrophage infiltration and focal perivascular chronic inflammation, with myelin degradation and degenerating axons. A month later, T2 hyperintensity extended into the right midbrain; two months later, it extended into the right thalamus and basal ganglia. Plasma exchange and another gram of rituximab had no benefit. Design/Methods: NA Results: NA Conclusions: This case is atypical for anti-MOG antibody encephalomyelitis because of the poor response to immunosuppression. This usually monophasic entity presents in younger patients who typically respond rapidly to steroids and plasma exchange. Long-term immunosuppression induces remission. The pathogenesis of anti-MOG encephalomyelitis is myelin destruction caused by antibodies to MOG. Here, B cell depletion with rituximab failed to improve symptoms or prevent relapses. Brain biopsy, before rituximab, showed scattered T lymphocytes and no B lymphocytes. Serum anti-MOG antibodies may sometimes be an epiphenomenon from myelin destruction by another process. Disclosure: Dr. Penyak Cipriani has nothing to disclose. Dr. Arndt has nothing to disclose. Dr. Pytel has nothing to disclose. Dr. Reder has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Bayer, Genzyme, Genentech. Dr. Reder has received personal compensation in an editorial capacity for Medlink. Dr. Reder has received research support from Biogen, Novartis, Bayer, Malinkrodt, Serono, Genentech. Dr. Javed has nothing to disclose.
Dual Effect of Propranolol on the Human Platelet Activation by Thrombin: Potentiation of Free Intracellular Ca2+ Mobilization and Inhibition of Phospholipase D Activity

Propranolol has been employed for a long time in clinical practice as non selective β-adrenoreceptor antagonist. Only the S(−) optical isomer has β-blocking activity, whereas R(+) form is totally ineffective. Early clinical observations (1978–1979) showed that treatment with propranolol improved blood platelet function in patients with cardiovascular diseases. In vitro studies indicated that this compound inhibited human PRP aggregation following exposure to ADP, collagen, epinephrine and Ca2+ ionophore A23187, and diminished aggregation of washed human platelets induced by a low concentration (0.025 U/ml) of thrombin (1). Both S(−) and R (+) isomers as well as (±) racemic form were active. Further studies evaluated the inhibitory effect of propranolol on phosphatidic acid (PA) phosphohydrolase, which converts PA to diacylglycerol in various type of cells (2). It was found that inhibition of PA phosphohydrolase by propranolol led to potentiation of 02 production in neutrophils stimulated with putative receptor agonist fMLP, suggesting a role for PA as a second messenger and for PA phosphohydrolase as a key regulatory enzyme in the interaction between PLC and PLD in the signal transduction (3,4). Sozzani et al., showed recently (5), that both S(−) and R(+) form inhibited protein kinase C (PKC) from human neutrophils and reduced [3H]PDBu binding by neutrophils in the concentration range of 100–200 μM.
Radiohalogenation of Monoclonal Antibodies: Experiences with Radioiodination of Monoclonal Antibodies for Radioimmunotherapy

At the National Institutes of Health, an apparatus was developed to radiolabel monoclonal antibodies for use in both imaging and radioimmuno-therapy. Up to 600 mCi of I-131 can be safely handled in this labeling hood which is shown schematically in Figure 1. The hood was designed so that two iodinations could be performed at the same time. Often these include specific and nonspecific (isotype matched) antibodies. To construct the apparatus, a standard fume hood was reinforced with steel and a steel frame was assembled inside the hood to support standard two inch lead bricks. The frame itself has two doors of steel encased lead. The entire apparatus is covered by a plexiglass safety box which has on its upper surface four fan and charcoal filter units to trap volatilized radioiodine. The internal components of the apparatus include a reaction vessel, a Sephadex gel filtration chromatography column, a gamma detector, product and waste vials, tubing and three-way stopcocks connecting these items, and a peristaltic pump. Small bore arterial pressure tubing (internal volume of 0.55 ml per 12 inch segment) with luer lock fittings connect the reaction vial to the column and the column to the product and waste vials. The reaction vial sits in a lead pig on top of a flat vortex mixer whose speed is controlled by a variable voltage supply. The peristaltic pump in the system is capable of driving fluid through the relatively rigid arterial pressure tubing at a rate of 1 ml per minute.
Spinal Cord and Peripheral Nervous System

Spinal cord and peripheral nerve injury (myelopathy), from radiation therapy can be transient or severe and debilitating, producing pain, paresthesias, sensory deficits, paralysis, Brown-Sequard syndrome, and bowel/bladder incontinence. The sympathetic system, the ganglia are located along paired chains on both sides of the vertebral column (the sympathetic trunk), as well as in three major collateral ganglia. The principal pathogenesis of injury is established to be due to vascular endothelial damage, glial cell injury, or both. Peripheral nerve damage by ionizing radiation has focused on the effect of single, high doses of radiation in animals, simulating the experience of intraoperative radiotherapy. Approximately 15 Gy IORT alone was observed to produce a 50 % reduction in the axon/myelin content. Magnetic resonance imaging (MRI) is typically the imaging modality of choice for assessing malignancies involving the spinal cord and brachial plexuses and detecting and diagnosing cord myelopathy. The use of various chemotherapy agents during radiotherapy has been shown to increase the radiosensitivity of the spinal cord. Toxicity increases when intrathecal chemotherapy is combined with systemic therapy with CNS irradiation. Radiation therapy to the spinal cord and peripheral nerves can induce myelopathy, typically characterized by pain, paralysis, and paresthesias. The risk of myelopathy primarily depends on the total radiation dose and dose per fraction, although the volume irradiated, underlying disease, concurrent therapies, and previous irradiation may also play a role. For external beam radiotherapy (EBRT) to the spinal cord in 2 Gy daily fractions, the risk of myelopathy appears low (<0.2 %) at 50 Gy and modest (<10 %) at 60 Gy, with an approximately 50 % risk of myelopathy at 70 Gy. Due to the severe consequences of myelopathy, clinical dose limits, i.e., shield at 40 Gy, have been used which carry a low (<0.2 %) risk of toxicity. The risk of radiation-induced brachial plexopathy is <1 % for a total dose of 50 Gy or less. For intraoperative radiotherapy (IORT) to the lumbosacral and brachial plexus, the threshold dose for injury appears to be 15–20 Gy. For single-fraction stereotactic radiosurgery to the spine, the risk of radiation-induced myelopathy appears low (well under 5 %) when the maximum point dose to the cord is ≤14 Gy, though the number of patients is small and the follow-up short at present.
An Alphabet-Reduction Algorithm for Chordal n-Grams

Computational music theorists have long been concerned with ways to parse musical surfaces into workable chords that conform to music-theoretical intuitions. This study proposes an algorithm that groups surface structures into relational networks that balance a chord’s contextual position and its scale-degree content. Applying the algorithm to a corpus of thousands of MIDI files that stretch throughout the common practice successfully derives an intuitive chord alphabet. The study raises issues concerning traditional harmonic-function theory, suggests a potential model of listeners’ learning of tonality’s basic cognitive elements, and proposes to a method of reducing surface complexity in corpus studies.
Determination of Sulfite in Food by Flow Injection Analysis

A method is described for the determination of sulfite levels in food products by flow injection analysis (FIA). The method is based on the decolorization of malachite green by SO2, which is isolated from the flowing sample stream by means of a gas diffusion cell. The FIA method has a detection limit in food sample extracts of 0.1 ppm SO2 (3 times peak height of blank), which corresponds to 1-10 ppm SO2 in a food product, depending on the extraction procedure used. At the 5 ppm SO2 level in a food extract, the precision of replicate injections is +/- 1-2%. The method was tested on a variety of both sulfite-treated and untreated food products and the results compared favorably with those obtained by the Monier-Williams, colorimetric (pararosaniline), and enzymatic (sulfite oxidase) methods. The average differences from the FIA results were 19, 11, and 12%, respectively, for those samples (n = 12) above 50 ppm SO2. At lower levels the results were somewhat more erratic due to inaccuracies of the various methods at low concentrations.
Coastal homeowners in a changing climate

As climate changes, coastal homeowners are potentially crucial actors in reducing the risks to property and human life from rising seas and increased hurricane activity. Absent strict, enforceable regulations mandating retrofitting of existing homes or major changes in homeowner insurance requirements, coastal resilience in a changing climate will largely reflect private, voluntary decisions of millions of individuals. However, research is scarce on the extent of structural vulnerabilities among US coastal homes and the mitigation measures that homeowners are taking or plan to take. Research devoted to disaster preparedness routinely neglects the specific actions of homeowners as consumers of structural mitigation products, despite the fact that such mitigation is the most cost-effective means to reduce losses. We attempt to fill this important gap with a new Coastal Homeowner Survey and indices designed to measure structural vulnerabilities and homeowner actions and intentions to address vulnerabilities. We conducted a pilot study of 662 respondents in one of the most frequently exposed US coastal communities, New Hanover County, North Carolina. We find that, on average, homes are minimally protected, with homeowners taking few actions to address structural vulnerabilities and not considering taking further action. We also find that the perceived cost of mitigation cannot sufficiently explain the lack of action, implying that other factors are at play. Subsequent research will use the remaining pilot survey data to analyze correlates of these indices to inform private and public sector stakeholders on how to incentivize risk reduction through structural mitigations.
Glass Chemistry Development Strategy for Hanford High-Level Waste

Developing glass compositions for Hanford high-level waste (HLW) is complicated by several factors. Hanford HLWs are stored in 177 underground storage tanks and have a wide range of compositions, some of which are not well-known. Further, decisions about retrieving, blending, and pretreating Hanford tank wastes are not final.