cssi/SciSciGPT-SciSciNet huggingface dataset:
Physician-assisted death in chronic neurologic diseases.

In the United States, a growing number of states have legalized physician-assisted death (PAD) since Oregon's pioneering law 20 years ago.1 PAD is also and more accurately called physician-assisted suicide. Currently, nearly 20% of United States citizens live in jurisdictions in which PAD is lawful (Oregon, Washington, Montana, Vermont, California, Colorado, and the District of Columbia). In Canada in 2016, federal legislation permitted PAD for patients with a “serious and incurable illness, disease, or disability” that causes intolerable suffering and as a result of which death was “reasonably foreseeable.”2
Cardiometabolic healthy obesity paradigm and all-cause mortality risk.

Abstract Objective To examine the cardiometabolic healthy obesity paradigm as it relates to all-cause mortality risk, with effect moderation evaluated for physical activity and demographic characteristics. Methods Data from the 1999–2006 NHANES were used. The analytic sample included 7579 dietary fasting adults (20 + yrs). All-cause mortality was linked with participant data from the National Death Index. Metabolic health was based on fasting levels of triglycerides, high-density lipoprotein cholesterol, glucose and blood pressure. Weight status was determined from measured height and weight. Physical activity was assessed via self-report. Six mutually exclusive groups were evaluated, including 1) Metabolically Healthy and Normal Weight (Referent), 2) Metabolically Healthy and Overweight, 3) Metabolically Healthy and Obese, 4) Metabolically Abnormal and Normal Weight, 5) Metabolically Abnormal and Overweight, and 6) Metabolically Abnormal and Obese. A Cox proportional hazards model was used to evaluate the association between these 6 groups and all-cause mortality. Results The unweighted median follow-up was 103 months; 770,568 person-months occurred with an incidence rate of 1.18 deaths per 1000 person-months. When compared to those who were metabolically healthy and of normal BMI, all other metabolic and weight configurations had an increased mortality risk. There was no evidence of effect modification by physical activity or demographic characteristics. Conclusions These findings emphasize the importance of optimizing body habitus and increasing public awareness of the detrimental effects of metabolic abnormalities.
Kaufman, Scott Barry and Carolyn Gregoire. Wired to Create: Unraveling the Mysteries of the Creative Mind: New York: TarcherPerigee Penguin Random House, 2016 (288 pp.; $17.00, paperback; ISBN 97803991755664)

University of Pennsylvania creativity scholar Scott Barry Kaufman and Huffington Post senior editor Carolyn Gregoire have teamed up to write a comprehensive and well-researched book in which messy ...
‘My drive is my sacred time’: commuting as routine liminality

ABSTRACTCommuting is a twice-daily routine for many workers. As it is situated between work and home, the commute is liminal, serving as a transition between the two realms while not belonging fully to either. In this paper, I show how many workers use the generative nature of routines to make commuting into a valuable and meaningful time that allows them to have time to themselves and pursue activities they cannot otherwise do. Commuting serves an important function by providing an excusable outlet for activities – reading for pleasure, listening to the radio, or daydreaming – which may be important for upholding work and social structures but often do not have a place within them. Such activities are able to take place because of the liminality of commuting, but also go beyond liminality through their routine nature. Through routine liminality, this paper contributes to organization studies research on liminality.
Predictive modeling and scalability analysis for large graph analytics

Many HPC and modern large graph processing applications belong to a class of scale-out applications, where the application dataset is partitioned and processed by a cluster of machines. Assessing the application scalability is one of the primary goals during such application implementation. Typically, in the design phase, programmers are limited by a small size cluster available for their experiments. Therefore, predictive modeling is required for the analysis of the application scalability and its performance in a larger cluster. While in an increased size cluster, each node will process a smaller portion of the original dataset, a higher communication volume between a larger number of nodes may cripple the application scalability and provide diminishing performance benefits. One of the main challenges is the analysis of bandwidth demands due to an increased communication volume in a larger size cluster. In this paper1, we introduce a novel regression-based approach to assess the scalability and performance of a distributed memory program for execution in a large-scale cluster. Our solution involves 1) a limited set of traditional experiments performed in a small size cluster and 2) an additional set of similar experiments performed with an “interconnect bandwidth throttling” tool, which exposes the bandwidth impact on the application performance. These measurements are used in creating an ensemble of analytical models for performance and scalability analysis. Using a linear regression approach, step by step, we incorporate into the model the following important parameters: i) the number of cluster nodes and application processes, ii) the dataset size, and iii) interconnect bandwidth. We demonstrate our solution, its power, and accuracy using a popular Graph500 benchmark, which implements a Breadth First Search algorithm on large, synthetically generated graphs. By utilizing measurements collected in a 32-node cluster, we are able to project the program performance in a large size cluster with hundreds of nodes. The proposed approach and derived models help to provide an early feedback to programmers on the scalability and efficiency of their solution.
Group A Streptococcal Adhesion

Streptococcus pyogenes, the group A streptococcus (GAS), is a common human pathogen that causes a wide array of infections, ranging from uncomplicated pharyngitis and pyoderma to invasive infections including sepsis, pyomyositis and fasciitis, pneumonia and toxic shock syndrome. Two nonsuppurative sequelae, acute rheumatic fever (ARF) and acute glomerulonephritis (AGN), are the most significant health problems stemming from GAS infection worldwide and account in large part for the intense clinical interest in this pathogen over the years. In the United States and other developed countries, where the incidence and severity of these diseases had declined over much of the 20th century,15,19 there has been a remarkable resurgence in the number of ARF cases over the last 10 years.60,69,70 In addition, a new clinical entity, streptococcal toxic shock syndrome has been described.58
Failure Is Inevitable: The Trade-off Between Missing Data and Maintenance

Fixing sensor faults is intuitively important, but in a class of applications where the environment is easily disturbed, there is a trade-off: maintenance requires disruption of the phenomena, so that for a period after maintenance the measurements made are not meaningful. An instance of such an application is soil monitoring. Because of its spatial heterogeneity, in-situ sensing via wireless sensor networks is a natural fit to monitoring soils. However, deploying a sensor below ground requires disturbing the soil. After a settling time, which can be weeks or more, measurements can then be trusted to reflect the state of the soil prior to excavation. Maintenance requires a similar operation, and affects all nearby sensors, not simply the one being fixed. In the San Jacinto Mountains, soil monitoring sensors were deployed to measure the flux of CO2 from the ground to the atmosphere. The deployment consisted of several sites, where each site monitored soil temperature, moisture, and CO2 concentration at multiple depths. The sensors within a site were within a few centimeters of each other. This chapter addresses the trade-off between fixing a broken sensor, and leaving it broken, by designing and implementing a system to both fill in missing data and keep the scientist informed about the need for maintenance. The result is potentially half as much maintenance, which translates into far more reliable data being collected.
Topical antimicrobial prophylaxis in colorectal surgery for the prevention of surgical wound infection: a systematic review and meta-analysis

Unfortunately, an author name (Nuzhat Iqbal) was missed out in the original publication. The complete updated author list is given below.
To Read or Not to Read, That Is the Question!.

If we were to poll people who are consid ered successful in today's society as to the most important subjects they had learned in school, they would probably mention mathematics and reading, and not neces sarily in that order. To most people, the abilities to read and to think mathemati cally are probably the two most valuable skills learned in school. Most quantitative information is encountered in written form, and it must be read to be understood. Be fore people can attempt to solve a problem (and problem solving is crucial to all of mathematics), they must read it and com prehend what it is about. Several research ers have found a high correlation between problem solving in mathematics and com prehension in reading. And yet, the impor tant area of reading in mathematics is largely overlooked by many mathematics teachers. For those students neither physio logically nor neurologically impaired, the subject matter teachers are best qualified to provide effective instruction in reading in their own subject fields. The written language of mathematics is conveyed through almost all of our instruc tional media?the chalkboard, the over head projector, but especially the textbook. Even hands-on materials in a mathematics laboratory setting usually require the abil ity to read directions or activity cards that accompany an experiment. The difficulties that students have in reading mathematics go hand in hand with the skills that are necessary for reading mathematics. In or der to help students read mathematics, sev eral activities can be used in the mathe matics classroom. Careful and continued use of these activities will help to sharpen the reading skills of most students. Keep in mind that mathematics is a combination of symbols, both verbal and numerical. We want our students to be able to shift back and forth from verbal to numerical sym bols as they read. It is necessary, for example, to alert stu dents to the fact that not all mathematics is read from left to right. Simple expressions such as
Abstract TMP91: White Matter Lesion Progression and Cognitive Function Over 5-Years in a Young Susceptible Population

Introduction: Cerebrovascular disease (CVD) and vascular risk factors cluster in families of patients with early-onset coronary artery disease (CAD). In a prior cross-sectional study of 714 healthy...
Carbon-Fiber Microbiosensor for Monitoring Rapid Lactate Fluctuations in Brain Tissue Using Fast-Scan Cyclic Voltammetry.

Recent studies have described a role for lactate in brain energy metabolism and energy formation, challenging the conventional view that glucose is the principle energy source for brain function. To date, lactate dynamics in the brain are largely unknown, limiting insight into function. We addressed this by developing and characterizing a lactate oxidase-modified carbon-fiber microelectrode coupled with fast-scan cyclic voltammetry. This new tool boasts a sensitivity for lactate of 22 ± 1 nA·mM–1 and LOD of 7.0 ± 0.7 μM. The approach has enabled detection of rapid lactate fluctuations with unprecedented spatiotemporal resolution as well as excellent stability, selectivity, and sensitivity. The technology was characterized both in vitro and in vivo at discrete recording sites in rat striatum. We provide evidence that striatal lactate availability increases biphasically in response to electrical stimulation of the dopaminergic midbrain in the anesthetized rat. This new tool for real-time detection of lactat...
Union College, Schenectady and the New York State Lottery in the 19th Century

This paper details the history of the workings of the New York State lottery in the 1st half of the 19th century, especially how it affected the operations of Union College in Schenectady, New York.
Technical Architecture to Deepen Our Solar System Awareness

This chapter deals with individual assets involved in discovery of NEOs. Past, current and future surveys are described, with their diverse technical architectures and objectives. In addition to the ground-based telescopes that deliver the most discoveries, past, current and future space-based missions are presented. Current limits for discovery are defined by the aperture size of the telescope and the observing geometry and viewing angle of a telescope, with the Earth representing an obstruction that avoids looking closer to the Sun. The smallest NEOs are still discovered only incidentally; ground-based telescopes cannot reach asteroids with orbits mostly inside the Earth’s orbit. Long periodic comets remain a low-level threat. Discovery and follow-up have migrated from manual efforts and individual observers toward an automated regime and large dedicated discovery surveys, supported by software development and automated processing of large data.
Anesthetic management of children with congenital insensitivity to pain with anhidrosis

Introduction Congenital analgesia is a rare autosomal recessive hereditary disease. The primary damage of congenital analgesia is central structure damage of comprehensive pain perception. Case presentation A 1-year-old Han Chinese boy was admitted to hospital because of a tongue bite. He had no response to noxious stimulation of the body surface and was diagnosed with congenital analgesia. A small dose of remifentanil was intravenously injected during anesthetic induction to reduce the stress response caused by endotracheal intubation. A certain depth of anesthesia should be guaranteed during anesthetic induction and surgery to alleviate the stress response induced by endotracheal intubation and the operation. Conclusion Opioid analgesics are not required for general anesthesia in patient with congenital insensitivity to pain. With a heat dissipation barrier in patients with congenital insensitivity to pain with anhidrosis, body temperature, end-tidal carbon dioxide and bispectral index should be monitored.
Significance of increased tissue transglutaminase expression in androgen-refractory prostate carcinoma

4106 Prostate cancer is the second most common cancer in males in the United States. Although androgen ablation remains the standard treatment for prostate cancer, the progression to hormone refractory disease becomes inevitable - occurring within 2-5 years. Androgen refractory prostate cancer (AIPC) cells acquire resistance to drugs and can no longer be cured by conventional therapy of any type. Therefore, understanding molecular mechanisms which contribute to the progression of androgen-sensitive prostate cancer to AIPC is likely to reveal new targets for effective treatment of prostate cancer. In this context, our initial observations that AIPC cell lines (DU145 and PC3) express high basal levels of the multifunctional protein, transglutaminase type-2 (TGm2), may be of interest. Indeed, increased expression of TGm2 has been reported in many aggressive forms of cancers and is implicated in development of drug-resistant and metastatic phenotype. In order to determine the significance of increased TGm2 expression in AIPC cells, we induced ectopic expression of TGm2 in TGm2-deficient LnCap cells by adenoviral-TG2 construct infection. Overexpression of TGm2 resulted in androgen-independent growth of LnCaP cells as established by their culture in charcoal-stripped serum and MTS assay. Moreover, TGm expression induced the activation of cell survival signaling pAkt pathway in LnCaP cells. Furthermore, TGm2 expression in LnCap cells was associated with increased invasiveness through the Matrigel transmembrane inserts. Conversely, we studied the effect of TGm2 downregulation in PC3 AIPC cells. Interestingly, downregulation of endogenous TGm2 by siRNA in AIPC PC3 cells reversed their sensitivity to therapeutic drugs. Prolonged downregulation of TGm2 induced cell death in PC3 cells. These results clearly suggest that aberrant expression of TG2 plays a critical role in promoting in cell survival and invasive functions in prostate cancer cells and therefore may represent an important factor in development of AIPC phenotype.
Marine vehicles simulated SAR imagery datasets generation

Remote sensing of marine vehicles is involved with object detection, tracking, and classification. This task is a real challenge in the maritime environment. In recent years, the deep learning techniques are demonstrated to be effective classifiers for this purpose, however, they need to be trained properly using rich training datasets that are rarely publicly available. To overcome this limitation, there is a need for a large-scale multi-look dataset of marine vehicles while take account of different sensor ranges, azimuth and elevation observation perspectives, operating contexts, ocean and atmospheric conditions, and marine vehicle type and wakes models. In this study, we used IRIS electromagnetic modeling and simulation system for virtualization of such a maritime environment and test vehicles and created different scenarios signifying the requirements. Through this approach, we initially construct and employ the physics-based CAD models of the test marine vehicles and their corresponding wake formation patterns that realistically represent their operating signature in the marine environment. Next, we apply our specific remote sensing techniques (i.e., EO/IR, SAR, and LIDAR) to generate unique multimodality synthetic imagery of the test marine vehicles. To evaluate and verify the effectiveness of this approach, we compared our generated simulated marine vehicle imagery with those images of the corresponding physical remote sensors. In this paper, we discuss the technical aspects of this work and detail our primarily evaluations of the obtained results.
Reinventing Public Administration for a Dangerous Century

The first two decades of this century have shown there is no simple formula for governing well. Leaders must make difficult choices about national priorities and the broad lines of policy – that is, about the substance of their strategy for governing. These strategic choices have important implications for public administration. Scholars in this field should study the processes by which strategy is formulated and executed more closely than they have over the last thirty years. A new agenda for public administration should emphasize processes of top-level decision-making, mechanisms to improve foresight and the management of societal risks, and problems of large-scale reorganization and inter-governmental coordination, among other topics. Many of these themes have been examined more closely by researchers in Canada than by those abroad. This difference should be recognized an advantage rather than a liability.
Mindfulness Practices in Supervision: Training Counselors’ Experiences:

The purpose of this qualitative study was to develop a descriptive understanding of couple and family counseling trainees’ experiences of using mindfulness techniques in their group supervision cou...
Racial Discrimination, Racial Identity, and Obesity in Collegiate African American Women

To investigate relationships among racial discrimination, explicit racial identity, and obesity in young collegiate African American (AA) women aged 18–25. Researchers recruited 136 women who self-identified as AA from a large Midwestern university. Racial discrimination (RD) was measured using lifetime overt experiences of discrimination, recent microaggressions, and vicarious RD directed towards close others. Explicit racial identity included dimensions of private regard, public regard, and centrality. Generalized obesity (elevated body mass index) and abdominal obesity (increased fat distribution in the midsection) were measured biometrically using kg/m2 and waist circumference, respectively. Hierarchical multiple regression was employed to explore main and interaction effects. After controlling for adverse life events and income, overt RD, recent microaggressions, and private regard directly accounted for variance in both BMI and waist circumference. Public regard and centrality moderated relationships between RD variables and waist circumference. RD and racial identity accounted for up to 13% of variance in BMI and waist circumference in main effects models among young collegiate AA women. While obesity is a multifactorial phenomenon, racial discrimination and racial identity may affect observed racial disparities in obesity rates among young women.
How China expanded its protected areas to conserve biodiversity

How has the global network of protected areas developed - and which decisions have guided this development? Answering these questions may give insight into what might be possible in the next decade. In 2021, China will host the Convention of Biological Diversity's Conference, which will influence the coming decade's agenda. We consider how China expanded its protected areas in the last half-century. Did concerns about biodiversity protection drive those decisions, or were other factors responsible? Like other countries, China has protected remote places with few people that are unusually cold or dry or both. Despite that, species with small geographical ranges that have the highest risk of extinction are better protected than expected. Importantly, while the growth of total area and number of protected areas has slowed for the last decade, increases in protection of forested ecosystems and the species they contain have steadily increased. China's future reserve expansion must consider where to protect biodiversity, not just how much area to protect.
Flow-driven right-to-left cardiac shunting in a patient with carcinoid heart disease and patent foramen ovale without elevated right atrial pressure: a case report and literature review.

Background Carcinoid heart disease is present in approximately 20% of the patients with carcinoid syndrome and is associated with poor prognosis. It usually manifests with right-sided valvular involvement including tricuspid insufficiency and pulmonary stenosis. Patent foramen ovale (PFO) is present in approximately 50% of the patients with carcinoid heart disease which is twice higher than the general population. Right-to-left shunting through a PFO can occur either due to higher right atrial pressure than left (pressure-driven) or when the venous flow is directed towards the PFO (flow-driven) in the setting of normal intracardiac pressures. We report a rare case of flow-driven right-to-left atrial shunting via PFO in a patient with carcinoid heart disease. Case summary A 54-year-old male with a metastatic neuroendocrine tumour to liver presented with progressive shortness of breath for 5 months. Patient was found to be hypoxic with oxygen saturation of 78% and examination revealed a holosystolic murmur. Arterial blood gas showed oxygen tension of 43 mmHg. A transthoracic and transoesophageal echocardiogram showed aneurysmal inter-atrial septum with a PFO, severe tricuspid regurgitation directed anteriorly towards the inter-atrial septum leading to a marked right-to-left shunt. Right heart catheterization showed right atrial pressure of 8 mmHg, mean pulmonary artery pressure of 12 mmHg, and normal oxygen saturations in the right atrium, right ventricle, and pulmonary arteries. The patient then underwent closure of the PFO along with tricuspid valve and pulmonary valve replacement at an experienced cardiovascular surgical centre and has been asymptomatic since. Conclusion Right-to-left shunting through a PFO in patients with normal right atrial pressure can be successfully treated with closure of the PFO. Thus, understanding the mechanism of intracardiac shunts is important to accurately diagnose and treat this rare and fatal condition.
Peroxisome Proliferator Activator Receptor Gamma Coactivator-1α Overexpression in Amyotrophic Lateral Sclerosis: A Tale of Two Transgenics

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of voluntary muscle function due to death of motor neurons. Energy metabolism deficits at the level of mitochondrial function have been implicated in the pathogenesis of ALS. We have previously reported improved motor function and survival in the SOD1G93A mouse model of ALS by neuron-specific over-expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of mitochondrial biogenesis. As pharmacological intervention targeting PGC-1α would result in whole-body upregulation of this transcriptional co-activator, in the current study we investigated whether global expression of PGC-1α is beneficial in the ALS mouse model. Methods: We generated transgenic mice with PGC-1α transgene expression driven by the actin promoter. Transgene expression was confirmed by PCR. Findings: The wild-type, actin-PGC-1α, SOD1G93A and actin-PGC-1α/SOD1G93A mice generated by crossing the actin-PGC-1α and SOD1G93A transgenic lines were monitored for weight loss, motor performance by accelerating rotarod test and survival. Interestingly, there was no significant improvement in body weight, motor function or survival in SOD1G93A mice over-expressing actin-PGC-1α. Interpretation: Our previous studies showed, in the same mouse model, that PGC-1α ectopic expression under the NSE promoter significantly improved motor function and survival. A potential explanation for this difference is that the actin promoter does not induce, in the cells that are specifically relevant in mechanisms associated with ALS pathology, levels of PGC-1α relevant to disease pathophysiology. This evidence strongly supports future therapeutic approaches that target PGC-1α primarily in neurons. Funding: This study was supported by discretionary funding to GMP . Dr. Pasinetti holds a Senior VA Career Scientist Award. Declaration of Interest: No conflicts of interest exist for any of the authors. Ethical Approval: All animal protocols used in the study were approved by the Institutional Animal Care and Use Committee of the Icahn School of Medicine at Mount Sinai.
Reducing time-to-treatment in underserved Latinas with breast cancer: The Six Cities Study

BACKGROUND: The interaction of clinical and patient-level challenges following a breast cancer diagnosis can be a significant source of health care disparities. Failure to address specific cultural features that create or exacerbate barriers can lead to less-than optimal navigation results, specifically in Hispanic/Latino women. METHODS: To address these disparities, the study leaders in San Antonio, Texas, and 5 other regional partners of the federally-funded Redes En Accion: The National Latino Cancer Research Network developed a culturally-tailored patient navigation intervention model for Latinas with breast cancer. RESULTS: Compared with control patients, a higher percentage of navigated subjects initiated treatment within 30 days (69.0% versus 46.3%, P = .029) and 60 days (97.6% versus 73.1%, P = .001) following their cancer diagnosis. Time from cancer diagnosis to first treatment was lower in the navigated group (mean, 22.22 days; median, 23.00 days) than controls (mean, 48.30 days; median, 33.00 days). These results were independent of cancer stage at diagnosis and numerous characteristics of cancer clinics and individual participants. CONCLUSIONS: Successful application of patient navigation increased the percentage of Latinas initiating breast cancer treatment within 30 and 60 days of diagnosis. This was achieved through navigator provision of services such as accompaniment to appointments, transportation arrangements, patient telephone support, patient-family telephone support, Spanish-English language translation, and assistance with insurance paperwork.
Nature's Information and Harmonic Proportion

The history of science is polarized by debates over Plato and Aristotle's holism versus the atomism of Democritus and others. This includes the complementarity of continuous and discrete, one and the many, waves and particles, and analog or digital views of reality. The three-fold method of the Pythagorean paradigm of unity, duality, and harmony enables the calculation of fundamental physical constants required by the forces of nature in the formation of matter; thereby demonstrating Plato's archetypal viewpoint.
Timing high performance kernels through empirical compilation

There are a few application areas, which remain almost untouched by the historical and continuing advancement of compilation research. For the extremes of optimization required for high performance computing on one end, and embedded systems at the opposite end of the spectrum, many critical routines are still hand-tuned, often directly in assembly. At the same time, architecture implementations are performing an increasing number of compiler-like transformations in hardware, making it harder to predict the performance impact of a given series of optimizations applied at the ISA level. These issues, together with the rate of hardware evolution dictated by Moore's Law, make it almost impossible to keep key kernels running at peak efficiency. Automated empirical systems, where direct timings are used to guide optimization, have provided the most successful response to these challenges. This paper describes our approach to performing empirical optimization, which utilizes a low-level iterative compilation framework specialized for optimizing high performance computing kernels. We present results showing that this approach can not only provide speedups over traditional optimizing compilers, but can improve overall performance when compared to the best hand-tuned kernels selected by the empirical search of our well-known ATLAS package.
Assessments of species in the Australian South East Fishery can be sensitive to the method used to convert from size-to age-composition data

Information about the age-structure of the catch is one of the primary inputs to many of the methods of stock assessment currently applied to SEF species. Two methods for calculating the catch-, mean length-, and mean mass-at-age matrices from the data collected from the fishery are outlined. These methods are illustrated by applying them to data for blue grenadier, Macruronus novaezelandiae, and eastern school whiting, Sillago flindersi. The assessment and risk analysis results for blue grenadier are highly sensitive to the choice of method, whereas those for eastern school whiting are not. It is recommended that a method that allows for inter-annual variation in mean length- and hence mass-at-age should be the standard for SEF stock assessments but that sensitivity to alternative methods needs to be examined routinely.
PET imaging of acetylcholinesterase inhibitor-induced effects on α4β2 nicotinic acetylcholine receptor binding

ase inhibitors; physostigmine; galanthamine ABSTRACT Acetylcholinesterase inhibitors (AChEIs) are drugs that increase syn- aptic acetylcholine (ACh) concentrations and are under investigation as treatments for symptoms accompanying Alzheimer's disease. The goal of this work was to use PET imaging to evaluate alterations of in vivo a4b2 nicotinic acetylcholine receptor (nAChR) binding induced by the AChEIs physostigmine (PHY) and galanthamine (GAL). The a4b2 nAChR-specific radioligand ( 18 F)nifene was used to examine the effects of 0.1-0.2 mg/kg PHY, 5 mg/kg GAL, and saline in three separate experiments all performed on each of two rat subjects. A 60-min bolus-infusion protocol was used with drug adminis- tered after 30 min. Data from the thalamus and cortex were analyzed with a graphical model accounting for neurotransmitter activation using the cerebellum as a reference region to test for transient competition with bound ( 18 F)nifene. Significant ( 18 F)nifene displacement was detected in both regions during one PHY and both GAL studies, while no significant competition was observed in both saline studies. This preliminary work indicates the viability of ( 18 F)nifene in detecting increases in synaptic ACh induced by AChEIs. Synapse 00:000-000, 2013. V C 2013 Wiley Periodicals, Inc.
The nerve gap dilemma: a comparison of nerves repaired end to end under tension with nerve grafts in a primate model

The objective of this study was to compare, in a clinically relevant primate model, axon regeneration after epineurial repair under tension (15 mm gap) with interfascicular nerve grafts with the use of either standard microsuture techniques or a new interfascicular nerve graft technique termed fascicular tubulization that uses a hypoantigenic collagen membrane formed into a tube to approximate nerve ends. Electrophysiologic analysis demonstrated that the percentage of proximal axons that conducted across the repair site was greater in those nerves repaired under tension with epineurially placed sutures than in either of the tensionless repairs involving interfascicular graft techniques. The mean diameters of the regenerated axons repaired under tension with epineurial sutures were greater than those of the nerves repaired with interfascicular grafts, although the difference was not statistically significant. Interfascicular nerve grafting with tubulization using the current collagen tube resulted in regeneration equal to the sutured interfascicular nerve grafts. For modest defects (perhaps up to 3 to 4 cm in the adult), it seems advantageous to accept the modest tension associated with an epineurial repair rather than to use an autograft (or artificial graft) to achieve a tension-free repair.
Multiscale modeling of high explosives for transportation accidents

The development of a reaction model to simulate the accidental detonation of a large array of seismic boosters in a semi-truck subject to fire is considered. To test this model large scale simulations of explosions and detonations were performed by leveraging the massively parallel capabilities of the Uintah Computational Framework and the XSEDE computational resources. Computed stress profiles in bulk-scale explosive materials were validated using compaction simulations of hundred micron scale particles and found to compare favorably with experimental data. A validation study of reaction models for deflagration and detonation showed that computational grid cell sizes up to 10 mm could be used without loss of fidelity. The Uintah Computational Framework shows linear scaling up to 180K cores which combined with coarse resolution and validated models will now enable simulations of semi-truck scale transportation accidents for the first time.
Endorectal MRI after radiation therapy: questioning the sextant analysis.

Purpose: To evaluate whether the information gained by three coregistration systems (sextant, hemi-prostate, and whole gland) differs significantly, suggesting that one approach should be routinely favored over the others. Despite its known limitations, sextant is the generally accepted standard for magnetic resonance imaging (MRI) and biopsy coregistration; nevertheless, depending on the magnitude of localization errors, other options may be adequate. Materials and Methods: Institutional Review Board approval was obtained and the study was Health Insurance Portability and Accountability Act (HIPAA)-compliant. We identified 70 patients who underwent 1.5 T endorectal MRI of the prostate between 1999 and 2008 after external beam radiotherapy for prostate cancer. A single reader reviewed all T2-weighted images for the presence or absence of tumor. The performance of each approach was quantified using receiver operating characteristic (ROC) curve analysis. Transrectal ultrasound-guided sextant biopsies were used as a standard of reference. Results: The areas under the ROC curve indicating accuracy for each MRI approach were 0.63 (sextant), 0.68 (hemi-prostate), and 0.71 (whole gland). There was no statistically significant difference among these approaches. Conclusion: As expected, the point estimate was higher for the whole-gland approach, but not significantly. Reliable assessment of locally recurrent prostate cancer after external beam radiotherapy by endorectal MRI may be made using a sextant, hemi-prostate, or whole gland approach. The option for one or another approach should not be solely based on estimations of imaging accuracy, but on the purpose of the procedure. J. Magn. Reson. Imaging 2011;33:1086–1090. © 2011 Wiley-Liss, Inc.
A new test method for determining the fracture toughness of concrete materials

The Spiral Notch Torsion Test (SNTT) determines the intrinsic fracture toughness (KIC) of structural materials by applying pure torsion to cylindrical specimens having a notch line that spirals around the specimen at a 45° pitch. KIC values are obtained with the aid of a 3-D finite-element computer code, TOR3D-KIC. The SNTT method is suitable for testing a wide variety of materials used extensively in pressure vessel and piping structural components and weldments, as well as ceramic and graphite materials. One important characteristic of SNTT is that neither a fatigue precrack nor a deep notch is required for evaluation of brittle materials, significantly reducing the sample size requirement. Results are reported for a Portland cement-based mortar demonstrating applicability of the SNTT method to cementitious materials. The estimated KIC of the tested mortar samples with compressive strength of 34.45 MPa was found to be 0.360 ± 0.017 MPa [radical sign]m.
A High-Salt Diet Dissociates NO Synthase-3 Expression and NO Production by the Thick Ascending Limb

NO produced by endothelial NO synthase (NOS3) decreases sodium transport by the thick ascending limb (THAL). We found previously that 7 days of high salt (HS) increased THAL-NOS3 expression but not NO production. NOS3 phosphorylation regulates enzyme activity. We hypothesized that HS acutely increases NOS3 expression and NO production, and, over time, changes in NOS3 phosphorylation dissociate NO production from expression. NOS3 expression increased by 71+/-13%, 127+/-24%, and 69+/-16% at days 1, 3, and 7 of HS, respectively. At days 14 and 28, expression was back to normal salt. After 1 day of HS, NO production in response to 250 micromol/L L-arginine was elevated by 146% and, by day 3, returned to normal salt. Similar increases were found in response to endothelin-1. Inhibitors of NOS1/2 did not blunt the salt-induced increase in NO. Phosphorylation at Thr495, an inhibitory site, decreased by 39+/-8% at day 1 of HS and then increased by 116+/-18% at day 3. Phosphorylation at Ser633 and Ser1177 (stimulatory sites) decreased by &25% at day 1 and remained depressed at day 3. Superoxide production increased by 71% at day 1, decreased by 57% at day 3, and decreased by 55% at day 7. The NOS inhibitor L-NG-nitroarginine methyl ester did not alter superoxide levels at any time point. The addition of reduced nicotinamide-adenine dinucleotide phosphate and tetrahydrobiopterin had no effect on NO release after 3 days of HS. We conclude the following: (1) HS transiently increases NO production and NOS3 expression; (2) NOS3 expression and NO production are dissociated by HS; and (3) changes in phosphorylation explain how THAL NOS3 activity and expression are dissociated by HS.
Pediatric use of antihypertensive medications: much more to learn

Abstract Background: Relatively few children require treatment for hypertension; those who do usually have underlying renal or other organ system disease. However, the awareness of childhood hypertension has been increasing, leading to a greater need for sound pediatric data on which to base treatment decisions. Objective: This article reviews the currently available pediatric data on the use of angiotensin-converting enzyme inhibitors, beta-adrenergic antagonists, calcium channel blockers, and other classes of antihypertensive medications in children, highlighting the areas in which better data are needed. Methods: Selected publications on the therapy of childhood hypertension were reviewed. Emphasis was placed on studies involving newer agents and on multicenter, controlled trials. Results: The amount of data available regarding the efficacy and tolerability of antihypertensive agents in children is limited but growing. Recent multicenter trials spurred by the 1997 US Food and Drug Administration Modernization Act frequently lack important pharmacokinetic data specific to the pediatric use of these drugs. Conclusions: Well-designed pediatric trials are needed not only to demonstrate drug efficacy in children, but also to elucidate drug kinetics and meticulously document whether the adverse effects that occur in children are different from those that occur in adults.
The dependence of aerosol effects on clouds and precipitation on cloud-system organization, shear and stability

Precipitation suppression due to an increase of aerosol number concentration in stratiform cloud is well-known. It is not certain whether the suppression applies for deep convection. Recent studies have suggested increasing precipitation from deep convection with increasing aerosols under some, but not all, conditions. Increasing precipitation with increasing aerosols can result from strong interactions in deep convection between dynamics and microphysics. High cloud liquid, due to delayed autoconversion, provides more evaporation, leading to more active downdrafts, convergence fields, condensation, collection of cloud liquid by precipitable hydrometeors, and precipitation. Evaporation of cloud liquid is a primary determinant of the intensity of the interactions. It is partly controlled by wind shear modulating the entrainment of dry air into clouds and transport of cloud liquid into unsaturated areas. Downdraft-induced convergence, crucial to the interaction, is weak for shallow clouds, generally associated with low convective available potential energy ( CAPE). Aerosol effects on cloud and precipitation can vary with CAPE and wind shear. Pairs of idealized numerical experiments for high and low aerosol cases were run for five different environmental conditions to investigate the dependence of aerosol effect on stability and wind shear. In the environment of high CAPE and strong wind shear, cumulonimbus- and cumulus-type clouds were dominant. Transport of cloud liquid to unsaturated areas was larger at high aerosol, leading to stronger downdrafts. Because of the large vertical extent of those clouds, strong downdrafts and convergence developed for strong interactions between dynamics and microphysics. These led to larger precipitation at high aerosol. Detrainment of cloud liquid and associated evaporation were less with lower CAPE and wind shear, where dynamically weaker clouds dominated. Transport of cloud liquid to unsaturated areas was not as active as in the environment of high CAPE and strong shear. Also, evaporatively driven differences in downdrafts at their level of initial descent were not magnified in clouds with shallow depth as much as in deep convective clouds as they accelerated to the surface over shorter distances. Hence the interaction between dynamics and microphysics was reduced, leading to precipitation suppression at high aerosol. These results demonstrate that increasing aerosol can either decrease or increase precipitation for an imposed large-scale environment supporting cloud development. The implications for larger-scale aspects of the hydrological cycle will require further study with larger-domain models and cumulus parameterizations with advanced microphysics. (Less)
A closer look at two AdS4 branes in an AdS5 bulk

We investigate a scenario with two AdS4 branes in an AdS5 bulk. In this scenario there are two gravitons and we investigate the role played by each of them for different positions of the second brane. We show that both gravitons play a significant role only when the turn-around point in the warp factor is approximately equidistant from both branes. We find that the ultralight mode becomes heavy as the second brane approaches the turn-around point, and the physics begins to resemble that of the RS model. Thus we demonstrate the crucial role played by the turn-around in the warp factor in enabling the presence of both gravitons.
Methoxycarbonyl-etomidate: a novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression.

Background Etomidate is a rapidly acting sedative-hypnotic that provides hemodynamic stability. It causes prolonged suppression of adrenocortical steroid synthesis; therefore, its clinical utility and safety are limited. The authors describe the results of studies to define the pharmacology of (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), the first etomidate analogue designed to be susceptible to ultra-rapid metabolism. Methods The gamma-aminobutyric acid type A receptor activities of MOC-etomidate and etomidate were compared by using electrophysiological techniques in human alpha1beta2gamma2l receptors. MOC-etomidate's hypnotic concentration was determined in tadpoles by using a loss of righting reflex assay. Its in vitro metabolic half-life was measured in human liver S9 fraction, and the resulting metabolite was provisionally identified by using high-performance liquid chromatography/mass spectrometry techniques. The hypnotic and hemodynamic actions of MOC-etomidate, etomidate, and propofol were defined in rats. The abilities of MOC-etomidate and etomidate to inhibit corticosterone production were assessed in rats. Results MOC-etomidate potently enhanced gamma-aminobutyric acid type A receptor function and produced loss of righting reflex in tadpoles. Metabolism in human liver S9 fraction was first-order, with an in vitro half-life of 4.4 min versus more than 40 min for etomidate. MOC-etomidate's only detectable metabolite was a carboxylic acid. In rats, MOC-etomidate produced rapid loss of righting reflex that was extremely brief and caused minimal hemodynamic changes. Unlike etomidate, MOC-etomidate produced no adrenocortical suppression 30 min after administration. Conclusions MOC-etomidate is an etomidate analogue that retains etomidate's important favorable pharmacological properties. However, it is rapidly metabolized, ultra-short-acting, and does not produce prolonged adrenocortical suppression after bolus administration.
A small heat-shock protein, p26, from the crustacean Artemia protects mammalian cells (Cos-1) against oxidative damage.

A small heat-shock protein (p26) purified from stress-resistant embryos of the crustacean, Artemia franciscana, was introduced into cultured cells of green monkey kidney (Cos-1) using the BioPORTER® delivery system. Cells containing p26 exhibited impressive resistance to hydrogen peroxide compared to controls. Introduction of the disaccharide trehalose did not provide protection against oxidative damage, but enhanced substantially the protective performance of p26 when both were present. These studies extend previous research on the protective role played by p26 in cells exposed to various forms of stress, presumably through its ability to function as a molecular chaperone.
Limonoids of calamondin seeds

Abstract Five new limonoids were isolated from calamondin seeds: methyl deacetylnomilinate (7), calamin (9), retrocalamin (10), cyclocalamin (11), and methyl isoobacunoate diosphenol (13). Structures were assigned on the basis of 1H and 13CNMR spectra, and chemical conversions of 9 to 10, 11, and 13. These reactions are also biogenetically plausible. Both 11 and the structurally similar limonoid rutaevin have been assigned the 5β-H configuration, which is opposite to that of all other known Rutaceae limonoids. 13CNMR data are presented for 15 limonoids.