cssi/SciSciGPT-SciSciNet huggingface dataset:
Drug release testing of long-acting intrauterine systems

Abstract Performance evaluation of polydimethylsiloxane (PDMS) based long-acting (e.g. 3–5 years) levonorgestrel (LNG) intrauterine systems (IUSs), such as Mirena®, is challenging due to their complex formulation, locally-acting feature, and extremely long duration of drug release. To achieve such long-term release, a large amount of drug (up to 52 mg in Mirena®) must be incorporated as a drug reservoir in the IUS. Consequently, dose dumping or unanticipated changes in the LNG-IUS in vivo release characteristics may give rise to adverse product safety and efficacy. Therefore, it is crucial to understand, and have appropriate control over, the physicochemical properties and in vitro release characteristics of these products. This requires an understanding of the LNG-IUSs drug release mechanism and the development of a sensitive yet robust in vitro release testing method. There have been no previous reports on in vitro drug release and the release mechanism from LNG-IUSs. This is probably a consequence of the extremely slow drug release rate of LNG-IUSs under real-time in-use conditions (e.g., 3–5 years) and therefore it is impractical to obtain complete release profiles (e.g. there is only 60% release in 5 years for Mirena®). Therefore, the development of appropriate accelerated in vitro release methods is imperative. Following preparation of LNG-IUSs, similar to Mirena®, real-time release was tested in (0.9% w/v NaCl) media in a water shaker bath at 37 °C for over 2 years. Addition of surfactant (sodium dodecyl sulfate (SDS)), elevation of temperature, addition of organic solvents (ethanol (EtOH), isopropanol (IPA), tert-butanol (TBA) and tetrahydrofuran (THF)) and a combination thereof were utilized as release media to accelerate drug release for LNG-IUSs. Complete drug release was achieved in 32 and 672 days in THF and TBA hydro-organic media, respectively. The release profile in THF was considered too fast as it may result in change of release mechanism, whereas the release profile in TBA was deemed suitable following model fitting. Model fitting was performed to understand the release characteristics as well as the release mechanisms. The release rate in the hydro-alcoholic media was linearly proportional to the swelling ratio of the PDMS in the corresponding organic solvents. Zero-order, first-order and two-phase models were utilized to fit the release profiles obtained under the different release conditions. The data analysis was comparable using the parameters from different models given the high R2 values. However, the two-phase model was better in terms of the release mechanism of the LNG-IUSs considering the full drug release profile. The present study will facilitate the process of granting of biowaivers through an in vitro approach, thus reducing the necessity for clinical studies. In addition, it will help reduce the regulatory burden without sacrificing product quality of LNG-IUS products.
Factors associated with high-cost hospitalizations in elderly ovarian cancer patients.

Abstract Objective To characterize factors associated with high-cost inpatient admissions for ovarian cancer. Methods Operative hospitalizations for ovarian cancer patients ≥65 years of age were identified using the 2010–2017 National Inpatient Sample. Admissions with high-cost were defined as those incurring ≥90th percentile of hospitalization costs each year, while the remainder were considered low-cost. Multivariable logistic regression models were developed to assess independent predictors of being in the high-cost cohort. Results During the study period, an estimated 58,454 patients met inclusion criteria. 5827 patient admissions (9.98%) were classified as high-cost. Median hospitalization cost for this high-cost group was $55,447 (interquartile range (IQR) $46,744–$74,015) compared to $16,464 (IQR $11,845–$23,286, p Conclusion High-cost ovarian cancer admissions were three times more expensive than low-cost admissions. Fewer open and extended procedures with subsequently shorter lengths of stay may have contributed to decreasing inpatient costs over the study period. In this cohort of patients largely covered by Medicare, clinical factors outweigh socioeconomic factors as cost drivers. Understanding the relationship of disease-specific and social factors to cost will be important in informing future value-based quality improvement efforts in gynecologic cancer care.
Automatic discovery of clinically interpretable imaging biomarkers for Mycobacterium tuberculosis supersusceptibility using deep learning.

Abstract Background Identifying which individuals will develop tuberculosis (TB) remains an unresolved problem due to few animal models and computational approaches that effectively address its heterogeneity. To meet these shortcomings, we show that Diversity Outbred (DO) mice reflect human-like genetic diversity and develop human-like lung granulomas when infected with Mycobacterium tuberculosis (M.tb) . Methods Following M.tb infection, a “supersusceptible” phenotype develops in approximately one-third of DO mice characterized by rapid morbidity and mortality within 8 weeks. These supersusceptible DO mice develop lung granulomas patterns akin to humans. This led us to utilize deep learning to identify supersusceptibility from hematoxylin & eosin (H&E) lung tissue sections utilizing only clinical outcomes (supersusceptible or not-supersusceptible) as labels. Findings The proposed machine learning model diagnosed supersusceptibility with high accuracy (91.50 ± 4.68%) compared to two expert pathologists using H&E stained lung sections (94.95% and 94.58%). Two non-experts used the imaging biomarker to diagnose supersusceptibility with high accuracy (88.25% and 87.95%) and agreement (96.00%). A board-certified veterinary pathologist (GB) examined the imaging biomarker and determined the model was making diagnostic decisions using a form of granuloma necrosis (karyorrhectic and pyknotic nuclear debris). This was corroborated by one other board-certified veterinary pathologist. Finally, the imaging biomarker was quantified, providing a novel means to convert visual patterns within granulomas to data suitable for statistical analyses. Implications Overall, our results have translatable implication to improve our understanding of TB and also to the broader field of computational pathology in which clinical outcomes alone can drive automatic identification of interpretable imaging biomarkers, knowledge discovery, and validation of existing clinical biomarkers. Funding National Institutes of Health and American Lung Association.
Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β-Lactam Antibiotics in Critically Ill Children

There has been increasing interest in incorporating β-lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration-versus-time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach. A prospective observational study was conducted in a single-center pediatric intensive care unit, where pediatric patients administered at least 1 dose of cefepime, meropenem, or piperacillin/tazobactam and who had residual blood scavenged from samples obtained for routine clinical care were enrolled. A total of 138 samples from 22 pediatric patients were collected in a 2-week period. For all 3 antibiotics, the samples collected covered the entire dosing intervals and were not clustered around specific times. There was high variability in the free concentrations and in the percentage of drug bound to protein. There was less than 15% degradation for meropenem or piperacillin when stored in whole blood or plasma at 4°C after 6 days. Cefepime degraded by more than 15% after 3 days. The opportunistic sampling approach is a powerful and feasible method to obtain sufficient samples to study the variability of drug concentrations and protein binding for future pharmacokinetic studies in the pediatric critical care population.
Usage of In Vitro Metabolism Data for Drug-Drug Interaction in Physiologically Based Pharmacokinetic Analysis Submissions to the US Food and Drug Administration

The key parameters necessary to predict drug-drug interactions (DDIs) are intrinsic clearance (CLint ) and fractional contribution of the metabolizing enzyme toward total metabolism (fm ). Herein, we summarize the accumulated knowledge from 53 approved new drug applications submitted to the Office of Clinical Pharmacology, US Food and Drug Administration, from 2016 to 2018 that contained physiologically based pharmacokinetic (PBPK) models to understand how in vitro data are used in PBPK models to assess drug metabolism and predict DDIs. For evaluation of CLint and fm , 29 and 20 new drug applications were included for evaluation, respectively. For CLint , 86.2% of the PBPK models used modified values based on in vivo data with modifications ranging from -82.5% to 2752.5%. For fm , 45.0% of the models used modified values with modifications ranging from -28% to 178.6%. When values for CLint were used from in vitro testing without modification, the model resulted in up to a 14.3-fold overprediction of the area under the concentration-time curve of the substrate. When values for fm from in vitro testing were used directly, the model resulted in up to a 2.9-fold underprediction of its DDI magnitude with an inducer, and up to a 1.7-fold overprediction of its DDI magnitude with an inhibitor. Our analyses suggested that the in vitro system usually provides a reasonable estimation of fm when the drug metabolism by a given CYP pathway is more than 70% of the total clearance. In vitro experiments provide important information about basic PK properties of new drugs and can serve as a starting point for building a PBPK model. However, key PBPK parameters such as CLint and fm still need to be optimized based on in vivo data.
Red Media, Blue Media, Trump Briefings, and COVID-19: Examining How Information Sources Predict Risk Preventive Behaviors via Threat and Efficacy.

Upon the growing concern over a massive infodemic and politicization of health issues during the COVID-19 pandemic, this study investigated how individuals' use of partisan media and Trump briefings, along with other information sources, predicts risk preventive behaviors. Drawing on the Extended Parallel Process Model (EPPM), our survey analysis (n= 1,106) revealed that those obtaining COVID-19 information from conservative media and Trump briefings were less likely to believe that COVID-19 is a serious threat (perceived threat) and that recommended preventive behaviors are effective and feasible (perceived efficacy). These beliefs, in turn, resulted in their decreased intentions to adopt risk preventative behaviors. In contrast, those who got COVID-19 information from liberal media, health organizations' briefings, and traditional media reported heightened threat and efficacy perception, which, in turn, led to their willingness to take risk preventive actions.
Observing flat wavefront formation with diffusive transport in microwave graphene with topological insulator protected edges

The Dirac singularity in 2D graphene structures theoretically allows pseudo-diffusive transport of photons or phonons, under which condition the energy propagates omnidirectionally, while a constant phase velocity is automatically guaranteed, enabling the formation of a uniform wavefront with a large beam aperture. Although similar phase-reconstruction effects were discussed for phononic graphene, none reported observing or taking advantage of the similar effect in microwave/photonic graphene. The challenge lies in the bulk edges where evanescent Bloch states emerge and interfere with the desired propagating Bloch state. We find that by adopting valley-constrained photonic topological insulator (PTI) protected borders and PTI waveguide, the proper modes are preserved, and we are able to experimentally observe the uniform wavefront generated in an all-dielectric microwave graphene bulk within a few wavelengths. This practically provides a possibility of developing low-profile devices with high directivity such as PTI horns or lenses.
Kidney Transplantation and Monoclonal Gammopathy of Undetermined Significance.

Plasma cell disorders are one of the most common hematologic malignancies. Monoclonal gammopathy of undetermined significance (MGUS) is defined by a serum monoclonal protein <3 g/dL, bone marrow plasma cell infiltration <10%, and most importantly absence of end-organ damage. The prevalence of MGUS in general population is estimated to be 1%-4% and its frequency increases with age with 3% among people above 50 y of age. The risk of progression to clinically significant plasma cell dyscrasia is estimated to be 1% per year. With aging population and increasing use of transplantation for the management of kidney disease in older adults, MGUS is being identified during the evaluation for kidney transplant candidacy or during the postkidney transplant follow-up. MGUS in patients with end-stage renal disease (ESRD) undergoing evaluation for kidney transplant can pose a complex management dilemma. In this article, we review the current state of knowledge about the prevalence of MGUS in ESRD population and the impact of kidney transplantation on the progression of MGUS to clinically significant plasma cell disorder. We make recommendations for the screening of ESRD patients undergoing kidney transplant evaluation and the management of MGUS after renal transplant.
AML-065: Measurable Residual Disease Status and FLT3 Inhibitor Therapy in Patients with FLT3-ITD-Mutated AML Following Allogeneic Hematopoietic Cell Transplantation

Context: In 2019, our transplant program initiated prospective FLT3-ITD measurable residual disease (MRD) monitoring by next-generation sequencing (NGS) of the peripheral blood or bone marrow throughout the first three months following HCT for all patients with FLT3-ITD-mutated AML undergoing HCT. We encouraged FLT3 inhibitor use as post-HCT maintenance. Objective: To evaluate the impact of post-HCT FLT3 MRD testing and FLT3 inhibitor use in a non-clinical trial setting. Design: Observational study of adults with FLT3-ITD-mutated AML who underwent allogeneic HCT at Stanford University between April 2019 and August 2020. Setting: Tertiary referral center. Patients or Other Participants: Thirty-six adults with FLT3-ITD-mutated AML are included in this study. Two patients were excluded from analyses due to early graft failure and receipt of azacitidine/enasidenib maintenance therapy. Interventions: Twenty-four patients (71%) received an FLT3 inhibitor after HCT, initiated a median of 2.8 months after transplant (range: 0.7–17.1). The median duration was 6.8 months (range: 1.1–18.8). Main Outcome Measures: Progression-free survival (PFS) and overall survival (OS). Results: Ten patients (29%) had detectable MRD within the first three months following HCT, while 24 (71%) patients remained MRD-negative. Although there was a trend toward inferior PFS for patients with early post-HCT MRD (p = 0.12), OS was not significantly impacted by MRD (p = 0.66). FLT3 inhibitor therapy improved PFS and OS, particularly in MRD-negative patients (maintenance vs no maintenance: PFS not reached vs 5.52 months, p = 0.002; OS not reached vs 5.85 months, p = 0.006). Conclusions: Clinical relapse can be prevented, even in patients with post-HCT MRD, by using early FLT3 inhibitor maintenance therapy, in keeping with the results from the SORMAIN trial. Real-time sensitive MRD testing allows clinicians to begin early initiation of FLT3 inhibitor therapy. This work was partially supported by the National Institutes of Health Grant UL1-TR003142 and Grant P30-CA124435.
Sustainability in Transportation Infrastructure: Perspective of CREATEs, Rowan University

This study presents an approach for improving sustainability in transportation infrastructure developed by the Center of Research and Education in Advanced Transportation Engineering Systems (CREATEs) of Rowan University. This approach consists of two major research components: (a) transportation safety and management and (b) pavement construction materials and practices. First, the effectiveness of the Street-Smart New Jersey pedestrian safety campaign—a behavioral change awareness and a public education campaign were assessed so as to improve compliance with pedestrian and motorist laws. Video data were obtained in eight communities across the state of New Jersey in 2018–2019. The efficiency of the campaign was evaluated by comparing the rates of non-compliant pedestrian and driver behaviors before and after the campaign. The second research component focused on improving the performance of cold in-place recycling (CIR) mixtures using a balanced mix design (BMD) approach. Eight mixtures were prepared at different asphalt contents, compaction efforts, and curing processes. Laboratory testing was conducted to assess the resistance of CIR mixtures to pavement distresses (rutting and cracking) and to select optimum contents of asphalt binders at which the performance of these mixtures is optimal. Three mixtures were then selected to construct full-scale CIR sections using foamed asphalt in varied contents: 2, 3, and 4% by total mix weight, at a constant water content of 3%. All the sections were instrumented with asphalt strain gages, pressure cells, and thermocouples to evaluate the mechanistic responses of each section. A heavy vehicle simulator (HVS) was utilized to apply loading on the pavement sections using: (a) a truck tire with a 40 kN load and (b) an aircraft tire with a 100 kN load. Multiple field tests and visual inspections were carried out to determine: (1) rut accumulation using a surface profiler (2) the structural integrity using a heavy weight deflectometer before and after APT testing, and (3) cracking potential by assessing sensors’ responses. Based on the outcomes of both research components, following the safety campaign can warrant considerable improvements in pedestrian and driver behaviors. In addition, the BMD approach can be used successfully to improve the resistance of CIR pavements to rutting and cracking.
LETMD1 is required for mitochondrial structure and thermogenic function of brown adipocytes.

Obesity and metabolic disorders caused by energy surplus pose an increasing concern within the global population. Brown adipose tissue (BAT) dissipates energy through mitochondrial non-shivering thermogenesis, thus representing a powerful agent against obesity. Here we explore the novel role of a mitochondrial outer membrane protein, LETM1-domain containing 1 (LETMD1), in BAT. We generated a knockout (Letmd1KO ) mouse model and analyzed BAT morphology, function and gene expression under various physiological conditions. While the Letmd1KO mice are born normally and have normal morphology and body weight, they lose multilocular brown adipocytes completely and have diminished mitochondrial abundance, DNA copy number, cristae structure, and thermogenic gene expression in the intrascapular BAT, associated with elevated reactive oxidative stress. In consequence, the Letmd1KO mice fail to maintain body temperature in response to acute cold exposure without food and become hypothermic within 4 h. Although the cold-exposed Letmd1KO mice can maintain body temperature in the presence of food, they cannot upregulate expression of uncoupling protein 1 (UCP1) and convert white to beige adipocytes, nor can they respond to adrenergic stimulation. These results demonstrate that LETMD1 is essential for mitochondrial structure and function, and thermogenesis of brown adipocytes.
Incremental Response of 3-D Cable Networks

A finite element analog to the nonlinear response of single cables to dynamic loadings has been introduced previously. The intent of this note is to extend the applicability of the finite element model previously presented to networks of intersecting cables in three dimensions. Toward that end, the nonlinear Hamilton’s principle in three dimensions for the incremental deformation of a cable element (including corrections to that used previously) is used to generate the linearized matrix analog for the incremental deployment, both static and dynamic, of the cable net. The solution processes for both the forced nonlinear dynamic response and the static nonlinear response of networks are given. In addition, a method for determining the natural frequencies and modes of free vibration of networks about arbitrary equilibrium positions is developed. Examples in three dimensions are used to verify and illustrate those solution methods.
Die Ausnutzung des Brennstoffs im Hochofen

Wie schon erwahnt, kann der Hochofen als ein gewaltiger Gaserzeuger angesehen werden, der in der Umgebung der Windformen aus festem Kohlenstoff und heiser Luft gewohnliches Generatorgas macht. Wahrend des Aufstiegs im Ofen wird das Gas durch den Sauerstoff der Beschickung, dessen Menge fur die Tonne Roheisen fast konstant ist, teilweise oxydiert und nimmt auserdem aus den Karbonaten der Beschickung Kohlendioxyd auf. Trotzdem enthalten aber die nicht oxydierten, noch brennbaren Bestandteile der entweichenden Gase einen sehr grosen, oft auch den grosten Teil des gesamten Heizwertes des Brennstoffs.
Canonical Equation K49 for Normalized Spectral Functions of a Product of Random Unitary Matrices

In this chapter, we analyze the spectral properties of the product of unitary independent matrices in the case where the number of matrices increases and every matrix, in some probability sense, converges to the identity matrix of increasing order. Such matrices resemble the unitary matrizant, which converges to a matrix of infinite dimension. Such matrices are used in many applied sciences, especially in the theory of gyroscopes, control theory and physics. In this section, we follow the method developed by V. A. Marchenko and L. A. Pastur [MaP]. This method is based on the differences of two normalized traces of resolvents of random matrices and on the derivation of a certain partial differential equation
Stability of Regression‐Based Monte Carlo Methods for Solving Nonlinear PDEs

The regression-based Monte Carlo methods for backward stochastic differential equations (BSDEs) have been the object of considerable research, particularly for solving nonlinear partial differential equations (PDEs). Unfortunately, such methods often become unstable when implemented with small time steps because the variance of gradient estimates is inversely proportional to the time step (σ2∼ 1/Δ t). Recently new variance reduction techniques were introduced to address this problem in~a paper by the author and Avellaneda. The purpose of this paper is to provide a rigorous justification for these techniques in the context of the discrete-time BSDE scheme of Bouchard and Touzi. We also suggest a new higher-order scheme that makes the variance proportional to the time step (σ2∼Δ t). These techniques are easy to implement. Numerical examples strongly indicate that they render the regression-based Monte Carlo methods stable for small time steps and thus viable for numerical solution of nonlinear PDEs.© 2016 Wiley Periodicals, Inc.
Saturated photon detection efficiency in NbN superconducting photon detectors

In this work, we demonstrate saturated photon detection efficiency with narrow NbN nanowires and SNAPs to boost the signal-to-noise ratio, and we demonstrate a stabilizing choke inductance that is part of the optically-active area.
Towards Balance-Affinity Tradeoff in Concurrent Subgraph Traversals

Graph technologies have been widely utilized for building big data analytics systems. Since those systems are typically wrapped as service providers in industry, it is critical to handle concurrent queries at runtime by incorporating a set of parallel processing units. In many cases, such queries result in local subgraph traversals, which essentially require an efficient scheduling scheme to explore the trade off between the workload balance and the task affinity. In this paper, we present an auction based approach for allocating concurrent subgraph traversals onto the processors. A dynamic weighted bipartite graph is built to model the affinity between subgraph traversals and processors, and the workload of processors. In particular, an edge between a task and a processor in the bipartite graph represents that the data needed by this task is likely cached by this processor. The task vertices and edges are dynamically added or removed, and the heavier edge weight represents stronger belief of the affinity. Besides, the edge weight is also governed by the current workload of the corresponding processor. We perform a parallel auction algorithm to figure out a near-optimal assignment of the subgraph traversal tasks onto the processors, which therefore addresses both the workload balance and the task affinity. The auction algorithm is performed incrementally, so as to capture the changes of the bipartite graph structure. Our experiments show the superior performance of the proposed method for various real-world use cases based on concurrent subgraph traversals.
Minding the Gap: Legal Ideals and Strategic Action in State Legislative Hearings

A recurring theme of sociolegal studies is how legal procedures function to reproduce social inequality by disadvantaging less powerful groups. However, there is little research about how disadvantaged groups achieve occasional victories in legal settings. Using transcripts of state legislative committee hearings in which birth activists seek certification or licensure for independent midwifery, I identify and investigate five ways in which legal ideals structure interaction and rhetoric in legislative hearings. While these ideals are instantiated in ways that disadvantage less powerful groups, activists can be seen adapting to this context by developing strategies to play law's ideals to their advantage. Such findings develop our understanding of how the gap between law's ideals and legal procedures can provide opportunities for collective activity seeking social change.
HAT tool for fluxless OLB and TAB

Methods and tool sets have been developed to allow fluxless OLB of high lead count TAB (tape automated bonding) components. The hot air thermode (HAT) is such a fluxless process. It can be used for most SMT components and is also well suited for TAB applications. HAT is a pick, place, and reflow system that uses high-velocity heated gas as the medium for solder melting and a dead reckoning method for package placement. Because of the particular tool/process integration employed by the HAT system, the technique does not require ovens with tightly controlled atmosphere and produces solder joints with excellent properties. Elimination of flux also eliminates flux application and cleaning steps during bonding, along with the solvents associated with the flux cleaning. Other advantages of this process include minimized emission during bonding and reduced bond corrosion, since corrosion due to entrapped flux residue is eliminated. The reliability of the solder joints produced by this method are discussed, along with process window data that demonstrate the use of the technique. >
The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival

The mammalian response to stress is complex, often involving multiple signalling pathways that act in concert to influence cell fate. To examine potential interactions between the signalling cascades, we have focused on the effects of a model oxidant stress in a single cell type through an examination of the relative influences of mitogen-activated protein kinases (MAPKs) as well as two proposed apoptosis regulators, nuclear factor kappaB (NF-kappaB) and Bcl-2, in determining cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose-dependent induction of apoptosis accompanied by sustained activation of all three MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2-induced apoptosis was markedly enhanced when ERK2 activation was selectively inhibited by PD098059. Apoptosis decreased when JNK/SAPK activation was inhibited by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had no effect on cell survival. Because NF-kappaB activation by H2O2 is potentially related to both the ERK and JNK/SAPK signalling pathways, we examined the effects of inhibiting the activation of NF-kappaB; this interference had no effect on the cellular response to H2O2. Overexpression of the anti-apoptotic protein Bcl-2 significantly decreased the apoptosis seen after treatment with H2O2 without altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK act in opposition to influence cell survival in response to oxidative stress, whereas neither p38 nor NF-kappaB affects the outcome. Bcl-2 acts independently and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells.
The Physiology of Color Vision

This is a review of certain recent advances in the study of the physiological mechanisms that mediate color perception. Data obtained from studies of the function of single nerve cells are emphasized. Also emphasized are those areas in which a consensus of opinion exists. Of particular significance are recent findings on the spectral sensitivity of single photoreceptors and on the central interactions that modify signals originating in the photoreceptors.
Igreja e tradição: opções e obstruções ecumênicas

Entre o protestantismo e o catolicismo romano o desafio ecumenico reside em diferentes concepcoes de tradicao e nao na relacao de Escritura versus tradicao. O entendimento protestante de tradicao remonta a Irineu de Lyon (sec. II), enquanto que a versao romana encontra sua primeira articulacao em Basilio de Cesarea (sec. V). A estas junta-se uma terceira acepcao de tradicao que tem sua origem em Prospero de Aquitaine (sec. V) e que hoje se expressa em uma vertente da Teologia da Libertacao bem como no movimento pentecostal. Estas versoes sao formalmente irreconciliaveis. O desafio ecumenico esta em reconhecer as diferencas e entender que a igreja e diversa e pluricentrica.
Symptoms in heart failure correlate poorly with objective haemodynamic parameters.

Summary Introduction: Even though heart failure (HF) is a very common condition, surprisingly little is known regarding association between patient’s symptoms and objective data. The purpose of this study was to evaluate for any correlations between haemodynamic, echocardiographic and laboratory data of presenting symptoms in HF patients. Methods: This study is a retrospective analysis of the limited access dataset from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial provided by the National Heart, Lung and Blood Institute. Symptoms including dyspnoea, orthopnoea, fatigue and gastrointestinal (GI) discomfort were graded by their severity from minimal (0) to maximal (3) on admission, at discharge, at 3 months and at 6 months from the admission. Results of Minnesota Living with Heart Failure (MLHF) score and assigned New York Heart Association (NYHA) functional class were available at the same time points. Results: A total of 433 patients with decompensated HF and decreased systolic function (ejection fraction < 30%) were included in this trial. Orthopnoea, dyspnoea and fatigue had weak correlation with invasive pulmonary artery systolic and diastolic pressure and negative correlation with serum creatinine, albumin, sodium, total bilirubin, haemoglobin and haematocrit; fatigue showed positive correlation to pulmonary artery pressures. Abdominal discomfort had no correlation to symptoms. There was no correlation of symptoms, NYHA class, or MLHF scores with age, gender, peak VO2 on cardiopulmonary stress test, body mass index, either right or left ventricular systolic function, B-type natriuretic peptide, cardiac output or cardiac index, troponin level, velocity of tricuspid regurgitation and multiple other factors predicting morbidity and mortality in HF. Conclusion: Overall, the correlation between symptoms and objective parameters was weak. Because of low magnitude of relationship between symptoms to objective parameters, it was concluded that there are likely other factors determining the perception of symptoms in HF patients.
Grade Inflation in Nursing Education: Proposed Solutions for an Ongoing Problem

PROBLEM The purpose of assigning grades at the conclusion of a course is to convey the level of achievement of learners. However, with the presence of grade inflation in nursing education, it poses a great threat to the evaluation process. PURPOSE The purpose of this article is to highlight the factors that influence grade inflation and to explore possible solutions to minimize the incidence of grade inflation in nursing education. FINDINGS A review of the literature revealed that a variety of factors influenced grade inflation and educators were indeed lenient with their grading practices, which hence attenuates the purpose of grading and evaluation. CONCLUSION While it may be an arduous task for nursing faculty to evaluate nursing students, nursing faculty have the obligation to preserve academic integrity and must devise appropriate solutions to address the incidence of grade inflation in nursing education.
A cell-density sensing factor regulates the lifetime of a chemoattractant-induced Gα-GTP conformation

Abstract Starving Dictyostelium discoideum cells monitor the local density of other starving cells by simultaneously secreting and sensing CMF. CMF regulates signal transduction through the chemoattractant cAMP receptor, cAR1. cAR1 activates a heterotrimeric G protein by stimulating Gα2 to release GDP and bind GTP. We show here that the rate of cAMP-stimulated GTP hydrolysis in membranes from cells exposed to CMF is roughly 4 times slower than in membranes from untreated cells, even though the rate of GTP binding is the same. This hydrolysis is abolished in cells lacking Gα2. Our data thus suggest that CMF regulates cAMP signal transduction in part by prolonging the lifetime of the Gα2-GTP complex. © 1997 Federation of European Biochemical Societies.
Abstract 2496: Identification and functional characterization of a novel oxidatively modified protein in the cardiac tissue after doxorubicin-induced cardiotoxicity.

Doxorubicin (Dox) is an anthracycline drug that is effectively used as a chemotherapeutic agent for the treatment of a variety of cancers. Its dose-dependent cardiotoxicity, however, has limited its chemoprotective properties in clinical practice. One of the primary mechanisms of Dox-induced cardiotoxicity is the generation of intracellular reactive oxygen species (ROS) by an iron-catalyzed reaction. We hypothesized that the consequent protein oxidation under oxidative stress can be monitored and correlated with cellular outcome of survival or death. First, to understand how Dox-induced oxidative stress is related to the cardiotoxicity, we identified specific cardiac proteins that are oxidatively modified under Dox-induced oxidative stress in a spontaneously hypertensive rat model of acute toxicity. Next we characterized the type(s) of modifications and the amino acid residues within the protein that undergo modification under oxidative stress. Finally, we investigated the functional consequences of such oxidative modifications. Based on our findings, we focused on protein carbonylation as an indicator of severe oxidative damage. We detected a highly carbonylated protein in the cardiac tissue after Dox-treatment. The Dox-induced carbonylated protein was identified as a cardiac myosin binding protein C (MyBPC) using mass spectrometry. To determine the carbonylated sites and effect of such modification in the protein structure and function, we expressed MyBPC in E. coli and purified recombinant MyBPC. Consistent with the in vivo results, recombinant MyBPC showed an increase in carbonylation under excessive oxidative conditions. The degree of carbonylation was time- and concentration-dependent. Excessive carbonylation was associated with the degradation of MyBPC. Identification of carbonylated sites and the effect of such carbonylation in the protein functions will help to better understand the Dox-induced cardiac toxicity. Our findings also indicate the potential for an oxidative biomarker for monitoring the Dox-induced cardiotoxicity. Citation Format: Baikuntha P. Aryal, Jinsook Jeong, V. Ashutosh Rao. Identification and functional characterization of a novel oxidatively modified protein in the cardiac tissue after doxorubicin-induced cardiotoxicity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2496. doi:10.1158/1538-7445.AM2013-2496
Effects of dizocilpine (MK-801) and ethanol on the EEG and event-related potentials (ERPS) in rats.

Recent neurophysiological data have suggested an interaction of ethanol (EtOH) with the glutamate-NMDA receptor complex. For instance, low levels of alcohol have been found to inhibit the ion current, activated by NMDA in in vitro preparations. The present study extends these paradigms in order to evaluate the electrophysiological effects of ethanol and the nonspecific NMDA receptor antagonist, dizocilpine (MK-801) in awake, conscious rats. Twenty Wistar rats were stereotaxically implanted with electrodes, aimed at dorsal hippocampus, amygdala, thalamus and frontal cortex. Rats received the following drugs: saline (s.c.), 0.01 and 0.1 mg/kg MK-801 (s.c.); EtOH, 0.75 g/kg (i.p.); 0.75 kg EtOH plus 0.01 mg/kg MK-801; 0.75 g/kg EtOH plus 0.10 mg/kg MK-801. Five minutes of EEG was collected and event-related potentials (ERPs) recorded in response to an auditory "oddball" paradigm. Spectral analysis revealed that MK-801 (0.1 m/kg) produced significant increases in low frequency EEG components, at all sites (1-6 Hz) and decreases in higher frequencies (16-32 Hz). Whereas ethanol (0.75 g/kg) produced decreases in power in all frequency bands. The combined administration of EtOH and MK-801 produced some antagonistic effects on the EEG in the low frequency range. Evaluation of ERPs revealed that MK-801 (0.1 mg/kg) produced significant decreases in amplitude of the N1 and P2 components in the cortex, decreases in the P1 and N2 in the thalamus and a profound decrease in the P3 components in hippocampus and amygdala. Ethanol was also found to produce decreases in the N1 component in cortex. The administration of MK-801 and ethanol together did not produce significant interactions on ERPs. These studies suggest that antagonism of the NMDA receptor by MK-801 may produce some effects similar to those of ethanol, however, their combined administration did not produce synergistic effects within these dose ranges.
Impact of the Red Pine Shoot Moth, Dioryctria resinosella (Lepidoptera: Pyralidae), on Height and Radial Growth in Wisconsin Red Pine Plantations

A newly described species, the red pine shoot moth, Dioryctria resinosella Mutuura, was found to be responsible for a decline in form of Pinus resinosa Ait. in central Wisconsin. Larval shoot feeding resulted in height and radial growth losses. Height growth losses were evaluated by comparison of growth in epidemic years with potential growth determined by a biological growth curve equation. Radial growth losses were evaluated by comparison of pre-outbreak growth to growth in outbreak years. Height growth loss estimates for various stands ranged from 38 to 65% over a 9-year epidemic period. Radial growth loss estimates ranged from 16 to 42% in the same stands over the same period.
Accurate molecular weight distribution of polymers using thermal field‐flow fractionation with deconvolution to remove system dispersion

Thermal field-flow fractionation (ThFFF) is an elution process that separates polymeric materials by molecular weight. Elution profiles thus provide approximations to the molecular weight distributions of polymers. The accuracy of such approximate distributions is expected to be improved by accounting for the effect on the elution profile of band-broadening processes in the FFF system. Fortunately this intrinsic band broadening, referred to as system dispersion, is theoretically well-defined in ThFFF. In this article we present an algorithm that corrects ThFFF elution profiles by removing system dispersion. The program is applied to ThFFF fractograms of standard polymers having both narrow and broad molecular weight distributions. The increased accuracy obtained by accounting for system dispersion is demonstrated. For the narrow standard, deconvolution shows that the polydispersity (weight/number-average mol. wt.) is only 1.004. For the broad standard, NBS 706, the molecular weight distribution and parameters obtained agree well with previously published results. Application to a simulated fractogram resulting from mixing five narrow standards helps define the conditions under which accurate molecular weight information can be recovered.
Influence of Humidified Aerosol on Lidar Depolarization Measurements below Ice-Precipitating Arctic Stratus

AbstractLidar measurements obtained during the Surface Heat Budget of the Arctic Ocean (SHEBA) experiment under a mixed-phase stratus cloud that was lightly precipitating ice show a range of surprisingly low depolarization ratios (4%–23%), despite an absence of cloud droplets there. These depolarization ratios are much lower than the range of theoretical values obtained for various ice habits. The depolarization ratios correlate well with radar reflectivity, suggesting that the variation in depolarization ratios results from variations in ice water content, rather than variation in ice habits or orientation. By calculating lidar depolarization based on (i) large-eddy simulations and (ii) in situ ice size distribution measurements, it is shown that the presence of humidified aerosol particles in addition to the ice precipitation can explain the distribution and vertical profile of the observed depolarization ratios, although uncertainties related to the aerosol size distributions are substantial. These cal...
The emotional roots of conspiratorial perceptions, system justification, and belief in the paranormal

Abstract We predicted that experiencing emotions that reflect uncertainty about the world (e.g., worry, surprise, fear, hope), compared to certain emotions (e.g., anger, happiness, disgust, contentment), would activate the need to imbue the world with order and structure across a wide range of compensatory measures. To test this hypothesis, three experiments orthogonally manipulated the uncertainty and the valence of emotions. Experiencing uncertain emotions increased defense of government (Experiment 1) and led people to embrace conspiracies and the paranormal (Experiment 2). Self-affirmation eliminated the effects of uncertain emotions on compensatory control (Experiment 3). Across all experiments, the valence of the emotions had no main effects on compensatory control and never interacted with the uncertainty of emotions. These studies establish a link between the experience of emotions and the desire for structure.
The structure of a mutant photosynthetic reaction center shows unexpected changes in main chain orientations and quinone position.

We report on the unexpected structural changes caused by substitution of acidic amino acids in the QB binding pocket of the bacterial photosynthetic reaction center by alanines. The mutations targeted key residues L212Glu and L213Asp of this transmembrane protein−cofactor complex. The amino acid substitutions in the L212Ala-L213Ala mutant reaction center (“AA”) were known to affect the delivery of protons after the light-induced generation of QB-, which renders the AA strain incapable of photosynthetic growth. The AA structure not only revealed side chain rearrangements but also showed movement of the main chain segments that are contiguous with the mutation sites. The alanine substitutions caused an expansion of the cavity rather than its collapse. In addition, QB is found mainly in the binding site that is proximal to the iron−ligand complex (closest to QA) as opposed to its distal binding site (furthest from QA) in the structure of the wild-type reaction center. The observed rearrangements in the struc...
Inhibition of XO or NOX attenuates diethylstilbestrol-induced endothelial nitric oxide deficiency without affecting its effects on LNCaP cell invasion and apoptosis.

Oestrogen protects cardiovascular health partially via an up-regulation of NO• (NO radical) production. Its synthetic analogue DES (diethylstilbestrol), used as a potent androgen deprivation therapy for patients with prostate cancer, is however associated with high incidence of thromboembolic events. Exposure of BAECs (bovine aortic endothelial cells) to pharmacologically relevant dosage (12.5 μmol/l, 24 h) of DES resulted in a marked reduction in endothelial NO• bioavailability determined by ESR (electron spin resonance), while 17β-oestradiol instead increased NO• production as expected. Intriguingly, endothelial O2•− (superoxide anion) production was up-regulated by DES in vitro and in vivo , which was, however, attenuated by the ER (oestrogen receptor) antagonist ICI 182780, the XO (xanthine oxidase) inhibitor oxypurinol or the NOX (NADPH oxidase) inhibitor NSC23766. These agents also restored NO• production. DES alone in a cell-free system did not produce any ESR-sound O2•− signal. Of note, eNOS (endothelial NO synthase) mRNA and protein remained unchanged in response to DES. These results suggest that receptor-dependent activation of XO or NOX, and subsequent production of O2•−, mediate DES-induced NO• deficiency. This could represent a previously unrecognized mechanism that is responsible for cardiovascular complications of DES administration. Importantly, DES-induced suppression of LNCaP cell invasion and apoptosis were not affected by XO or NOX inhibitor. Therefore combinatorial therapy of DES and XO/NOX inhibitor may prove to be an innovative and useful therapeutic option in eliminating cardiovascular complications of DES, while preserving its anti-cancer effects, benefiting patients with advanced cancer who do not respond well to any other treatments but DES. Abbreviations: BAEC, bovine aortic endothelial cell; BME, basal membrane extract; BrdU, bromodeoxyuridine; CMH, 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine; CVD, cardiovascular disease; DES, diethylstilbestrol; DHE, dihydroethidium; eNOS, endothelial NO synthase; ER, oestrogen receptor; ESR, electron spin resonance; FBS, fetal bovine serum; NO•, NO radical; NOX, NADPH oxidase; O2•−, superoxide anion; PEG, poly(ethylene glycol); PSA, prostate-specific antigen; ROS, reactive oxygen species; SOD, superoxide dismutase; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; XO, xanthine oxidase