cssi/SciSciGPT-SciSciNet huggingface dataset:
Tand, sjin, sigma, s, en ja

De letter S komt voor in bijvoorbeeld het woord tandarts. Maar vrijwel niemand weet dat dit teken zijn oorsprong heeft in een afbeelding van tanden.
Reconstitution of a KATP channel from basolateral membranes of Necturus enterocytes.

We have previously reported that basolateral membrane vesicles isolated from Necturus maculosa small intestinal epithelial cells and incorporated into planar phospholipid bilayers display a highly selective maxi-conductance K + channel whose open-time probability is affected by voltage. We now report that this channel is inhibited by MgATP in the solution bathing the intracellular face of the channel but not by Mg 2+ or the Na + or K + salts of ATP; the effects of MgATP can be prevented or reversed by MgADP. The channel is also inhibited by the nonhydrolyzable ATP analogue magnesium adenosine 5'-O-(3-thiotriphosphate) and the sulfonylurea derivatives tolbutamide and glibenclamide; all of these agents are effective in the intracellular compartment but not when added to the extracellular compartment alone. Channel activity is stimulated by the K + channel opener, diazoxide, which also reverses the effect of glibenclamide but not of MgATP. The possible role of this channel as a mediator of the parallelism between basolateral membrane Na + -K + pump activity and the macroscopic K + conductance of that barrier is discussed.
Life after PACE (Program of All‐Inclusive Care for the Elderly): A retrospective/prospective, qualitative analysis of the impact of closing a nurse practitioner centered PACE site

IntroductionThe Program of All‐Inclusive Care for the Elderly (PACE) was developed in San Francisco in the early 1970s to address the shortcomings of an ineffective healthcare delivery system for older adults with long‐term care needs living in the community (National PACE Association, 2011). PACE a
Selected hemostatic abnormalities associated with neoplastic disease.

Prominent hemostatic abnormalities seen in patients with malignant disease are highlighted. Primary emphasis on changes noted in fibrinolysis is based on the authors’ belief that these changes may relate directly to the spread of cancer as well as to potential therapeutic intervention.
Properties of transplantable reticulum cell sarcomas in SJL/J mice.

The transplantable reticulum cell sarcomas (RCS-5 and RCS-19 of SJL/J mice, derived in the Sloan-Kettering Institute for Cancer Research by Drs. Carswell and Old from spontaneous tumors in this strain, have two very unusual properties. Firstly, these tumor cells induce an extremely high proliferative response in syngeneic cells from normal, non-tumorous mice (1) and secondly, while they are readily transplantable in normal syngeneic hosts, they fail to grow if the mice have been irradiated prior to tumor cell injection (Carswell and Old, unpublished observations; 2,3). We are reporting here on studies aimed at elucidating: 1) The nature of the antigen which induces the strong T cell proliferation in both thymus and peripheral T cells (1); 2) The basis for the relatively limited but definite immunity which the SJL/J mice exhibit upon immunization (4); 3) That property of irradiated mice which prevents RCS growth; and 4) The nature and characteristics of the tumor cells themselves.
Simulation and modeling for the Stand-Off Radiation Detection System (SORDS) using GEANT4

A Stand-Off Radiation Detection System (SORDS) is being developed through a joint effort by Raytheon, Los Alamos National Laboratory, Bubble Technology Industries, Radiation Monitoring Devices, and the Massachusetts Institute of Technology, for the Domestic Nuclear Detection Office (DNDO). The system is a mobile truck-based platform performing detection, imaging, and spectroscopic identification of gamma-ray sources. A Tri-Modal Imaging (TMI) approach combines active-mask coded aperture imaging, Compton imaging, and shadow imaging techniques. Monte Carlo simulation and modeling using the GEANT4 toolkit was used to generate realistic data for the development of imaging algorithms and associated software code.
Clinical Management of Menopause-Related Sleep Disturbance

Sleep disturbances are common during the menopause transition. Women with vasomotor symptoms may be more at risk for insomnia, particularly if night sweats cause awakenings. Other sleep difficulties, such as difficulty with initiating sleep, and early morning awakening can also occur often in this population. Psychiatric disorders, involving depressive and anxiety symptoms, and medical issues such as obstructive sleep apnea, restless legs syndrome, and incontinence are also common in this population and can contribute to sleep difficulties. Any sleep disturbance, regardless of cause, can lead to daytime fatigue and can negatively impact functioning and quality of life, and therefore, identifying and treating insomnia in menopausal women is essential for their well-being. With many options of pharmacological and non-pharmacological treatments for insomnia, tailoring treatment to a patient’s particular sleep issue and preference is ideal. This chapter focuses on the assessment and treatment of insomnia in menopausal women utilizing typical clinical case examples.
Teledermatology: An updated overview of clinical applications and reimbursement policies

Telemedicine is an emerging field in healthcare that provides services from different medical specialties to patients all around the world. One of the specialties in telemedicine, teledermatology, has grown exponentially as a cost-effective way to implement dermatological healthcare to underserved areas and populations. This article reviews the literature that pertains to the cost-effectiveness, reliability, public access, patient satisfaction, and reimbursement policies of teledermatology. Teledermatology was found to be cost-effective and reliable in reducing in-person visits and time away from work, and allows for the faster delivery of care. However, reimbursement policies for teledermatology services are rather new and vary significantly from state to state. As public interest in and access to teledermatology continue to grow, the future of teledermatology depends on the development of new technology as well as quality improvement strategies and the evolution of sustainable reimbursement policies.
The Relationship Between and Factors Influencing Staff Nurses' Perceptions of Nurse Manager Caring and Exposure to Workplace Bullying in Multiple Healthcare Settings.

OBJECTIVEThe aim of this study was to examine the relationship between, and factors influencing, staff nurse perceptions of nurse manager caring (NMC) and the perceived exposure to workplace bullying (WPB) in multiple healthcare settings.BACKGROUNDWorkplace bullying is commonplace, increasing, and d
TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics.

Abstract Transactive response DNA-binding protein of 43 kDa (TDP-43) functions as a heterogeneous nuclear ribonucleoprotein and is the major pathological protein in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). TDP-43 pathology may also be present as a comorbidity in approximately 20–50% of sporadic Alzheimer’s disease cases. In a mouse model of MND, full-length TDP-43 increases association with the mitochondria and blocking the TDP-43/mitochondria interaction ameliorates motor dysfunction. Utilizing a proteomics screen, several mitochondrial TDP-43-interacting partners were identified, including voltage-gated anion channel 1 (VDAC1) and prohibitin 2 (PHB2), a crucial mitophagy receptor. Overexpression of TDP-43 led to an increase in PHB2 whereas TDP-43 knockdown reduced PHB2 expression in cells treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP), an inducer of mitophagy. These results suggest that TDP-43 expression contributes to metabolism and mitochondrial function however we show no change in bioenergetics when TDP-43 is overexpressed and knocked down in HEK293T cells. Furthermore, the fusion protein mitofusin 2 (MFN2) interacts in complex with TDP-43 and selective expression of human TDP-43 in the hippocampus and cortex induced an age-dependent change in Mfn2 expression. Mitochondria morphology is altered in 9-month-old mice selectively expressing TDP-43 in an APP/PS1 background compared with APP/PS1 littermates. We further confirmed TDP-43 localization to the mitochondria using immunogold labeled TDP-43 transmission electron microscopy (TEM) and mitochondrial isolation methods There was no increase in full-length TDP-43 localized to the mitochondria in APP/PS1 mice compared to wild-type (littermates); however, using C- and N-terminal-specific TDP-43 antibodies, the N-terminal (27 kDa, N27) and C-terminal (30 kDa, C30) fragments of TDP-43 are greatly enriched in mitochondrial fractions. In addition, when the mitochondrial peptidase (PMPCA) is overexpressed there is an increase in the N-terminal fragment (N27). These results suggest that TDP-43 processing may contribute to metabolism and mitochondrial function.
Early Childhood Clival-C2 Atypical Teratoid/Rhabdoid Tumor: Gross Total Resection Followed by Aggressive Chemotherapy and Radiation

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare and aggressive tumors that most often occur in early childhood. These tumors usually are located in the cerebellum or cerebral hemispheres, but can occur in unusual locations. Prior to genetic analysis demonstrating a deletion of the tumor suppressor gene INI-1, these tumors were often misdiagnosed as primitive neuroectodermal tumors (PNETs). The patient presented here is a 7 year-old boy with an extradural clival-C2 AT/RT who was treated with a gross total resection (GTR) using an aggressive transoral resection. He was then stabilized with a halo and an instrumented fusion from occiput to C5, and received adjuvant therapy consisting of chemotherapy, radiation therapy, and a bone marrow transplant with a stem cell rescue. The patient survived an additional 42 months after surgery before dying of disseminated disease. Given the very small number of extradural spinal AT/RTs, the best treatment and prognosis is unknown. However, an aggressive approach of GTR followed by intensive chemotherapy and radiation therapy regimens appears to provide the best option at this point in time.
Biochemistry of Bacterial Bioluminescence

Publisher Summary The luminous bacteria have been isolated from marine environments all over the world, both from seawater and from the light organs of certain fish and squid, and from nonmarine habitats as well. The recent taxonomic studies have placed the luminous bacteria in several major groups: marine forms in the genera Photobacterium, Beneckea and Alteromonas , and nonmarine forms in the genera Vibrio and Xenorhabdus . Among the marine luminous bacteria, Photobacterium species occur as symbionts within specialized light organs of higher organisms; Beneckea species have not been found associated with light organs, but members of both genera occur as gut symbionts. The ecology of the luminous bacteria and its relationship to the control of synthesis and expression of the luminescent system has recently been reviewed in some detail. This chapter discusses the present understanding of the reaction catalyzed by bacterial luciferase and the enzyme
Engineering of Mesoporous Silica Nanoparticles for In Vivo Cancer Imaging and Therapy

Mesoporous silica nanoparticles (MSNs) possess many attractive properties, such as good biocompatibility, large surface area, high pore volume, uniform and tunable pore size, and have been intensively investigated as novel drug delivery systems for more than 10 years. Although in vitro imaging and therapeutic applications by using MSNs have been reached a great success, transferring these to the in vivo level is still facing big challenges and is now under intensive investigations. In this chapter, we summarized the very recent progress and future directions of engineering MSNs for biological imaging and therapy in vivo.
Positive Divine Law in Austin

Austin is better understood as the last of the Schoolmen rather than the first of the Benthamites. Ostensibly, Austin fundamentally distinguishes the objective moral truth of divine law from the morally dubious human positive law. But at a deeper level, Austin distinguishes natural from positive law within human positive law just as he distinguishes natural from positive divine law. Like the Schoolmen, he uses the term positive in two very different senses, by implicit contrast both to natural law and to customary law. Once we see the importance of positive divine law, what Austin calls the “revealed” law of God, we can see that might makes duty and the Almighty makes all duty. True, utility provides the standard for judging the goodness or badness of all law, human and divine. But positive divine law imposes duties paramount to all others whether it is good or bad, because the existence of a law is one thing, its merit or demerit is another. In short, Austin has a divine command theory of duty but not of goodness.
Myosin heavy chain isoforms and smooth muscle function.

Isoforms of striated muscle myosin have a long history. They have been extensively studied on biochemical and functional levels and more recently in terms of molecular biology. Under various environmental stresses the architecture of the contractile apparatus of striated muscle can be remodelled to meet the imposed demands.
Fuel Cells: A Call for Total Design

In this issue of Joule, Andrew J. Steinbach and co-authors 1 are introducing an innovative design approach to overcome the barriers for reliable operation of fuel cells under most demanding high-power conditions. This work describes an unusual and elegant solution for water management: removing an excess cathode water product through the anode. It teaches us again that, in engineering design, all processes are interdependent, and the holistic view of the device components is the wise one.
Acute liver injury induced by red yeast rice supplement

A 64-year-old woman previously taking no medications presented with acute hepatitis 6 weeks after starting a red yeast rice supplement to decrease her cholesterol. Red yeast rice is commonly used for hyperlipidaemia as an alternative to statins as it contains monacolin K, the same active chemical in lovastatin. Infectious, toxic and autoimmune causes for injury were ruled out, and liver biopsy was consistent with drug induced liver injury. Red yeast rice appeared to be the cause of her hepatotoxicity. After stopping the supplement and initiating treatment with intravenous methylprednisolone, liver enzymes decreased towards baseline.
Intrinsic flow and tearing mode rotation in the RFP during improved confinement

We use charge exchange recombination spectroscopy to make the first localized measurements of impurity ion flow velocity profiles in the reversed field pinch. Measurements in improved confinement plasmas reveal an intrinsic flow profile that is peaked on the axis and mostly parallel to the equilibrium magnetic field. The toroidal flow decreases in time at off-axis locations where tearing modes are resonant, giving rise to a highly sheared flow profile near the axis. The tearing mode phase velocity correlates strongly with toroidal flow near the resonant surface and weakly with flow in other locations, providing an opportunity to verify the commonly held assumption that the plasma and mode move together at the resonant surface. Mechanisms for the observed momentum loss during the improved confinement period are evaluated, and it is found that eddy currents in the conducting shell caused by the rotation of the dominant tearing mode dominate over other losses.We use charge exchange recombination spectroscopy to make the first localized measurements of impurity ion flow velocity profiles in the reversed field pinch. Measurements in improved confinement plasmas reveal an intrinsic flow profile that is peaked on the axis and mostly parallel to the equilibrium magnetic field. The toroidal flow decreases in time at off-axis locations where tearing modes are resonant, giving rise to a highly sheared flow profile near the axis. The tearing mode phase velocity correlates strongly with toroidal flow near the resonant surface and weakly with flow in other locations, providing an opportunity to verify the commonly held assumption that the plasma and mode move together at the resonant surface. Mechanisms for the observed momentum loss during the improved confinement period are evaluated, and it is found that eddy currents in the conducting shell caused by the rotation of the dominant tearing mode dominate over other losses.
Ocean inspired mathematical art

I like to crochet hyperbolic surfaces, wavy sculptures or light features. They are hyperbolic as opposed to flat or spherical, which means that at every point, where the surface is hyperbolic, a ne...
ECONOMIC POLICY UNCERTAINTY AND THE REAL ECONOMY OF SINGAPORE

This paper investigates (for the first time) the impact of the economic policy uncertainties of Singapore and its major trading partners on Singapore’s industrial production and exports. The study ...
In vitro assembly of polioviruses: III. Assembly of 14 S particles into empty capsids by poliovirus-lnfected HeLa cell membranes

Abstract Rough membranes obtained from poliovirus-infected HeLa cells have the capacity to assemble 14 S particles into 73 S empty capsids in vitro . A corresponding fraction from uninfected cells did not possess this activity. When labeled 14 S particles were incubated with smooth membranes obtained from infected cells, a significant amount of radioactivity sedimented as heterogeneous material in the 30–70 S region of the gradient. Sucrose gradient analysis of 14 C-labeled rough and smooth membrane fractions lysed with deoxycholate (DOC) demonstrated the presence of 14 S particles, 73 S empty capsids, and a 110 S structure in the rough membrane fraction. These structures were found only in trace amounts in the smooth membrane fraction. In the absence of DOC treatment, no 14 S particles were found in any of the membrane fractions. The 73 S empty capsids, on the other hand, were detected in the presence or absence of DOC treatment in the rough-membrane fraction. Therefore, it appears that 14 S particles are associated with the rough membranes where they are assembled into 73 S empty capsids and/or complete virions.
Primary colon adenocarcinoma with choriocarcinoma differentiation: a case report and review of the literature

Choriocarcinoma is an aggressive malignancy of trophoblastic tissue, typically of gestational etiology. Sporadic, nongestational cases are rarely found outside of the gonads. There are only 31 cases of primary choriocarcinoma of the colon reported in the literature. As a consequence of their rarity and aggressive nature, timely diagnosis and effective treatment have proved challenging, and prognosis is very poor. For that reason, we present a rare case with prolonged survival in the youngest reported patient . A 26-year-old Caucasian woman presented with abdominal cramping and rectal and vaginal bleeding. Elevated serum human chorionic gonadotropin and an 8-cm right-sided mass seen on ultrasound suggested ectopic pregnancy. The patient was treated with methotrexate; however, her symptoms persisted, and her human chorionic gonadotropin levels continued to rise. Further workup showed a large mass of the sigmoid colon with multiple hepatic lesions suggestive of metastases. Preliminary pathology showed adenocarcinoma. Despite surgical resection and initiation of FOLFOX chemotherapy (folinic acid, fluorouracil, oxaliplatin), the patient had significant clinical deterioration, and her human chorionic gonadotropin increased exponentially. Further pathological review showed two distinct phenotypes: adenocarcinoma merging with choriocarcinoma. The result of evaluation of the metastatic lesions was also positive for choriocarcinoma. Treatment was promptly changed to a choriocarcinoma-targeting chemotherapy regimen of EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), resulting in rapid and dramatic response. The patient had mild progression after 1 year and was switched back to FOLFOX with bevacizumab. After five cycles, scans showed further progression, and the patient was started on third-line therapy with FOLFIRI (folinic acid, fluorouracil, irinotecan) and bevacizumab. Eighteen months after her diagnosis, the patient was alive and maintaining an overall response. Our patient achieved a marked response and prolonged survival. Although a comprehensive review of the literature showed that survival with these tumors has improved over the past 10 years, prognosis remains poor. Currently, there is no established algorithm for the management of these rare tumors, but both the literature and our patient’s case indicate that a choriocarcinoma-targeted regimen is critical for survival. Further evaluation of these rare tumors is warranted in order to identify pathological patterns that may help in the diagnosis, management, and survival of these malignancies.
Measurement and modelling of thermal and physical properties of wood construction materials

Abstract Construction materials exposed to fire conditions may decompose resulting in a loss of strength as well as contributing to the growth and size of the fire. Predicting the behavior of timber and other construction materials during a fire exposure requires accurate thermal modeling of the material considering both the effects of elevated temperature and material decomposition state (virgin to char) on the thermal and physical properties. This paper evaluates the use of different techniques to measure the porosity, permeability and thermal diffusivity of wood construction materials at different levels of decomposition due to a high temperature exposure. The porosity and thermal diffusivity values of wood exhibit similar changes with decomposition level. It was found that virgin and char material properties can be used in conjunction with thermogravimetric data to estimate material properties at intermediate decomposition levels. The findings can be used to reduce the number of experiments required to characterize other materials. Permeability was observed to be dependent on the structure and composition of the material. Scanning electron microscopy images revealed that decomposition increased the space between the otherwise compact-arranged elements (grain, particles), resulting in an increase in permeability. Consequently, permeability should be measured at different decomposition levels and direction to quantify the material changes due to a high temperature exposure.
Development of a particle collision algorithm for discontinuous Galerkin simulations of compressible multiphase flows

Abstract This paper discusses the development of algorithms for simulating compressible, four-way coupled, particle-laden flows with discontinuous Galerkin methods. Specifically, the algorithmic developments focus on the treatment of hard-sphere collisions. First, we aim to reduce the computational effort devoted to inspecting pairs of particles for collisions during the given time step. This is often one of the most expensive stages of four-way coupled particle-laden flow simulations. The proposed algorithm exploits information about relative particle positions provided by the geometric mapping of a physical element to a reference element commonly employed in discontinuous Galerkin and other finite-element-based solvers. Second, we develop an enhanced particle-wall collision methodology that better accounts for finite particle size than previously developed schemes. A particular feature of the particle-particle and particle-wall collision algorithms is compatibility with arbitrary, curved, unstructured elements. Finally, we apply the resulting framework to a number of test cases, including hypersonic dusty flow over an entry capsule and surface erosion by sandblasting.
Association Between Beta-Blockers and Mortality and Readmission in Older Patients with Heart Failure: an Instrumental Variable Analysis

The demographics of heart failure are changing. The rate of growth of the “older” heart failure population, specifically those ≥ 75, has outpaced that of any other age group. These older patients were underrepresented in the early beta-blocker trials. There are several reasons, including a decreased potential for mortality benefit and increased risk of side effects, why the risk/benefit tradeoff may be different in this population. We aimed to determine the association between receipt of a beta-blocker after heart failure discharge and early mortality and readmission rates among patients with heart failure and reduced ejection fraction (HFrEF), specifically patients aged 75+. We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of beneficiaries with ≥ 1 hospitalization for HFrEF between 2008 and 2016 to run an instrumental variable analysis. The primary measure was 90-day, all-cause mortality; the secondary measure was 90-day, all-cause readmission. Using the two-stage least squared methodology, among all HFrEF patients, receipt of a beta-blocker within 30-day of discharge was associated with a − 4.35% (95% CI − 6.27 to − 2.42%, p < 0.001) decrease in 90-day mortality and a − 4.66% (95% CI − 7.40 to − 1.91%, p = 0.001) decrease in 90-day readmission rates. Even among patients ≥ 75 years old, receipt of a beta-blocker at discharge was also associated with a significant decrease in 90-day mortality, − 4.78% (95% CI − 7.19 to − 2.40%, p < 0.001) and 90-day readmissions, − 4.67% (95% CI − 7.89 to − 1.45%, p < 0.001). Patients aged ≥ 75 years who receive a beta-blocker after HFrEF hospitalization have significantly lower 90-day mortality and readmission rates. The magnitude of benefit does not appear to wane with age. Absent a strong contraindication, all patients with HFrEF should attempt beta-blocker therapy at/after hospital discharge, regardless of age.
Individualized Glaucoma Change Detection Using Deep Learning Auto Encoder-Based Regions of Interest.

Author(s): Bowd, Christopher; Belghith, Akram; Christopher, Mark; Goldbaum, Michael H; Fazio, Massimo A; Girkin, Christopher A; Liebmann, Jeffrey M; de Moraes, Carlos Gustavo; Weinreb, Robert N; Zangwill, Linda M | Abstract: PurposeTo compare change over time in eye-specific optical coherence tomography (OCT) retinal nerve fiber layer (RNFL)-based region-of-interest (ROI) maps developed using unsupervised deep-learning auto-encoders (DL-AE) to circumpapillary RNFL (cpRNFL) thickness for the detection of glaucomatous progression.MethodsForty-four progressing glaucoma eyes (by stereophotograph assessment), 189 nonprogressing glaucoma eyes (by stereophotograph assessment), and 109 healthy eyes were followed for ≥3 years with ≥4 visits using OCT. The San Diego Automated Layer Segmentation Algorithm was used to automatically segment the RNFL layer from raw three-dimensional OCT images. For each longitudinal series, DL-AEs were used to generate individualized eye-based ROI maps by identifying RNFL regions of likely progression and no change. Sensitivities and specificities for detecting change over time and rates of change over time were compared for the DL-AE ROI and global cpRNFL thickness measurements derived from a 2.22-mm to 3.45-mm annulus centered on the optic disc.ResultsThe sensitivity for detecting change in progressing eyes was greater for DL-AE ROIs than for global cpRNFL annulus thicknesses (0.90 and 0.63, respectively). The specificity for detecting not likely progression in nonprogressing eyes was similar (0.92 and 0.93, respectively). The mean rates of change in DL-AE ROI were significantly faster than for cpRNFL annulus thickness in progressing eyes (-1.28 µm/y vs. -0.83 µm/y) and nonprogressing eyes (-1.03 µm/y vs. -0.78 µm/y).ConclusionsEye-specific ROIs identified using DL-AE analysis of OCT images show promise for improving assessment of glaucomatous progression.Translational relevanceThe detection and monitoring of structural glaucomatous progression can be improved by considering eye-specific regions of likely progression identified using deep learning.
Control of the Stefan System and Applications: A Tutorial

The so-called Stefan system describes the dynamical model of the liquid–solid phase change in materials ranging from water and ice in the polar caps to metal casting and additive manufacturing (3D ...
Chapter 9 Immunoassays for Modified Nucleosides of Ribonucleic Acids

Publisher Summary This chapter presents a survey of antibodies directed toward modified ribonucleosides and their basic and clinical applications. Immunoassay methodology for radioimmunoassays and enzyme linked immunosorbent assays applicable to modified nucleosides are presented.. These methods are used to characterize polyclonal and monoclonal antibodies directed toward the modified nucleosides N 6 -[9-( β -D-d)-6-ylcarbamoyl]-L-threonine, t 6 A; N6-(∆ 2 -isopentenyl)adenosine, i 6 A;2ʹ-O-methyl guanosine; and zeatin. Two illustrations are presented for quantitation of nucleoside levels using immunoassay technology. One is a method for quantitating levels of modified nucleosides in tRNAs from bacterial extracts, using as an example the Escherichia coli mutant miaA that is deficient in i 6 A derivatives. This procedure can be adapted to screening for either prokaryotic or eukaryotic cells deficient in a specific modification on transfer RNA (tRNA) or ribosomal ribonucleicacid (rRNA). Quantitation of levels of modified nucleosides in human urine is described and polyclonal antibodies directed toward three different modified nucleosides are studied using urine samples from normal subjects and patients with cancer. The nucleoside t 6 A shows promise for monitoring the transition to the metastatic stage for breast cancer patients.
Proton-pump inhibitor use is associated with lower urinary magnesium excretion.

Aims Although multiple recent studies have confirmed an association between chronic proton-pump inhibitor (PPI) use and hypomagnesaemia, the physiologic explanation for this association remains uncertain. To address this, we investigated the association of PPI use with urinary magnesium excretion. Methods We measured 24-hour urine magnesium excretion in collections performed for nephrolithiasis evaluation in 278 consecutive ambulatory patients and determined PPI use from contemporaneous medical records. Results There were 50 (18%) PPI users at the time of urine collection. The mean daily urinary magnesium was 84.6 ± 42.8 mg in PPI users, compared with 101.2 ± 41.1 mg in non-PPI users (P = 0.01). In adjusted analyses, PPI use was associated with 10.54 ± 5.30 mg/day lower daily urinary magnesium excretion (P = 0.05). Diuretic use did not significantly modify the effect of PPI on urinary magnesium. As a control, PPI use was not associated with other urinary indicators of nutritional intake. Conclusions Our findings suggest that PPI use is associated with lower 24-hour urine magnesium excretion. Whether this reflects decreased intestinal uptake due to PPI exposure, or residual confounding due to decreased magnesium intake, requires further study.
Axonal guidance and the development of muscle fiber-specific innervation in Drosophila embryos

The outgrowth of peripheral nerves and the development of muscle fiber-specific neuromuscular junctions were examined in Drosophila embryos using immunocytochemistry and computer-enhanced digital optical microscopy. We find that the pioneering of the peripheral nerves and the formation of the neuromuscular junctions occur through a precisely orchestrated sequence of stereotyped axonal trajectories, mediated by the selective growth cone choices of pioneer motoneurons. We have also examined the establishment of the embryonic muscle fibers and, using intracellular dye fills, have identified cells that are putative muscle pioneers. The muscle fibers of the bodywall have completed their morphogenesis prior to the initiation of synaptic contacts, and owing to the timing of neurite outgrowth from the CNS, synaptogenesis is synchronous at muscle fibers throughout the bodywall. At each muscle fiber the innervating axons make their initial contacts on a characteristic surface domain of the target cell's membrane. Through stereotyped growth cone-mediated trajectories the motoneurons actively establish the basic anatomical features of the mature neuromuscular junction, including the stereotyped, muscle fiber-specific branch anatomy. These events occur without significant process pruning or apparent synapse elimination. Our results suggest that the basic elements of the mature neuromuscular innervation, including the details of the ending trajectory on the target cell's surface, are formed by the precise navigation and presumed recognition by the motoneuron growth cones of muscle membrane surface features.
A least-squares regression based method for vehicle yaw moment of inertia estimation

Vehicle yaw moment of inertia is an important parameter for many vehicle dynamic models and control systems yet it is usually difficult to estimate. A methodology in estimating the vehicle yaw moment of inertia is presented in this article by studying the linear relationship between vehicle lateral acceleration, yaw acceleration, and rear wheel lateral tire forces. This linear relationship is derived by manipulating the equations in the single-track model such that the front wheel force disappears in the equation. Based on the linear relationship, the common global positioning system (GPS) measurement error—antenna bias angle, can be tuned based on the symmetric assumption of vehicle left and right dynamics and a least-squares regression (LSR). A lag-like lateral tire force model is applied to capture the transient dynamics of the lateral tire force. The parameter determining relaxation length of the tire model can also be tuned based on a similar LSR method. Finally, the yaw moment of inertia can be estimated from an LSR again after knowing the estimated rear wheel lateral force. Simulation results in CarSim® show that this proposed method is capable of generating reasonable estimations of yaw moment of inertia without knowing the front road wheel steering angle.
Structural dynamics of ribosome subunit association studied by mixing-spraying time-resolved cryogenic electron microscopy.

Ribosomal subunit association is a key checkpoint in translation initiation but its structural dynamics are poorly understood. Here, we used a recently developed mixing-spraying, time-resolved, cryogenic electron microscopy (cryo-EM) method to study ribosomal subunit association in the sub-second time range. We have improved this method and increased the cryo-EM data yield by tenfold. Pre-equilibrium states of the association reaction were captured by reacting the mixture of ribosomal subunits for 60 ms and 140 ms. We also identified three distinct ribosome conformations in the associated ribosomes. The observed proportions of these conformations are the same in these two time points, suggesting that ribosomes equilibrate among the three conformations within less than 60 ms upon formation. Our results demonstrate that the mixing-spraying method can capture multiple states of macromolecules during a sub-second reaction. Other fast processes, such as translation initiation, decoding, and ribosome recycling, are amenable to study with this method.
The topological structure of attractors for differentable functions

Recent research has shown that there is a significant cleavage between the structure of \(\omega\)-limit sets for continuous functions, and the structure of \(\omega\)-limit sets for Lipschitz functions. The development of these results rested on measure theoretic considerations. In this paper we show that there is no such divergence when one considers the topological structure of these two classes of \(\omega\)-limit sets. We show that an every nowhere dense compact set is homeomorphic to an \(\omega\)-limit set for a differentiable function with bounded derivative.
High-k gate dielectrics for scaled CMOS technology

This paper summarizes our results on several high-k gate dielectrics, including TiO/sub 2/, Ta/sub 2/O/sub 5/, ZrO/sub 2/, HfO/sub 2/, and Al-doped varieties of the above. Among them, TiO/sub 2/ and Ta/sub 2/O/sub 5/ have higher dielectric constants than others, while ZrO/sub 2/ and HfO/sub 2/ are thermodynamically more stable against the formation of SiO/sub 2/ on Si, and the addition of Al raises the temperature for crystallization for all of them. Both MOS capacitors and MOSFET's have been fabricated with these high-k gate dielectrics, and their properties have been studied. We have also utilized the temperature-dependent IN characteristics of these high-k dielectrics to study their current conduction mechanisms and to construct their energy band diagrams.
Run-Time Support for Multi-tier Programming of Block-Structured Applications on SMP Clusters

We present a small set of programming abstractions to simplify efficient implementations for block-structured scientific calculations on SMP clusters. We have implemented these abstractions in KeLP 2.0, a C++ class library. KeLP 2.0 provides hierarchical SMPD control flow to manage two levels of parallelism and locality. Additionally, to tolerate slow inter-node communication costs, KeLP 2.0 combines inspector/executor communication analysis with overlap of communication and computation. We illustrate how these programming abstractions hide the low-level details of thread management, scheduling, synchronization, and message-passing, but allow the programmer to express efficient algorithms with intuitive geometric primitives.
Lipopolysaccharide 3-Deoxy-d-manno-octulosonic Acid (Kdo) Core Determines Bacterial Association of Secreted Toxins

In contrast to cholera toxin (CT), which is secreted solubly by Vibrio cholerae across the outer membrane, heat-labile enterotoxin (LT) is retained on the surface of enterotoxigenic Escherichia coli (ETEC) via an interaction with lipopolysaccharide (LPS). We examined the nature of the association between LT and LPS. Soluble LT binds to the surface of LPS deep-rough biosynthesis mutants but not to lipid A, indicating that only the Kdo (3-deoxy-d-manno-octulosonic acid) core is required for binding. Although capable of binding truncated LPS and Kdo, LT has a higher affinity for longer, more complete LPS species. A putative LPS binding pocket is proposed based on the crystal structure of the toxin. The ability to bind LPS and remain associated with the bacterial surface is not unique to LT, as CT also binds to E. coli LPS. However, neither LT nor CT is capable of binding to the surface of Vibrio. The core structures of Vibrio and E. coli LPS differ in that Vibrio contains a phosphorylated single Kdo-lipid A, and E. coli LPS contains unphosphorylated Kdo2-lipid A. We determined that the phosphate group on the Kdo core of Vibrio LPS prevents CT from binding, resulting in the secretion of soluble toxin. Because LT binds E. coli LPS, it remains associated with the extracellular bacterial surface and is released in association with outer membrane vesicles. We propose that difference in the extracellular fates of LT and CT contribute to the differences in disease caused by ETEC and Vibrio cholerae.
Dual Diagnosis, Mutual-Help Use, and Outcomes: A Naturalistic Follow-Up

Objective: Individuals with dual diagnoses benefit from participation in mutual-help groups, though it is unclear how much such participation contributes to outcomes when accounting for utilization of treatment. Methods: We used mixed-model regressions to examine associations between participation in mutual-help groups reported at 6-month, 1-year, and 2-year follow-ups with substance use and psychiatric outcomes among outpatients with dual diagnoses (N = 304), while controlling for amounts of substance use disorder and mental health outpatient treatment. Results: Follow-up rates were 81%, 82%, and 84% at 6 months, 1 year, and 2 years, respectively. Mean involvement in mutual-help groups (scale of 0 to 14) ranged between 4.6 (SD = 4.5) and 6.1 (SD = 4.5). When controlling for baseline status and treatment amounts, more mutual-help group meeting attendance, F = 13.98, p < .001, and involvement, F = 19.32, p < .001, were associated with fewer days of alcohol use. Likewise, after controlling for baseline stat...
Potentiation of cholinergic activity with pyridino[1,2-a]imidazo[5,4-b]indole: in vitro studies.

Abstract 1. 1. Effects of a novel imidazoindole derivative on cholinergic function were studied in isolated tissue preparations. 2. 2. The compound demonstrated a dose-dependent (10 −11 –10 −9 ) potentiation (20–60%) of acetylcholine induced tension in guinea pig ileal tissue. 3. 3. Increases in the size of end-plate potentials and nerve evoked muscle twitches were observed in frog nerve-skeletal muscle preparations. 4. 4. Cholinesterase activity was not inhibited. 5. 5. The results suggest that the compound has actions at the post-synaptic muscarinic receptor complex in smooth muscle and causes pre-synaptic increases in ACh release at the neuromuscular junction.
GRAVES' IMMUNOGLOBULINS PROTECT THE HUMAN TSH RECEPTOR: FURTHER EVIDENCE FOR TSH RECEPTOR ANTIBODIES IN GRAVES' DISEASE

We have investigated whether membrane-bound TSH and Graves' immunoglobulins (Ig) were able to inhibit the action of the disulphide-reducing agent dithiothreitol (DTT) which reduced the binding of 125I-bTSH to thyroid membranes. Human thyroid (20,000 g fraction) was incubated with increasing concentrations of cold bTSH, washed and resuspended in 10 mmol/lDTT for 60 min at 37 degrees C. After the DTT was removed, 70-80% of the receptor-bound bTSH dissociated with 2 mol/l NaCl. In the absence of cold bTSH, 80% of the binding of receptor-purified 125I-bTSH was inhibited after membrane exposure to DTT but in the presence of bTSH-occupied receptor sites there was a dose related protection of the receptors, with 100% protection following incubation with 30 mU/ml bTSH. Like bTSH, immunoglobulin fractions from Graves' sera caused a time-dependent reduction in 125I-bTSH binding-inhibition after incubation and washing of thyroid membranes prior to ligand binding. Approximately 25-40% of this reduction was reversible by exposure to 2 mol/l NaCl. After pre-binding normal Ig to thyroid membranes, and subsequent incubation with DTT, there was no protection of TSH receptors. However, each of the Graves' Ig examined (n = 4) was able to provide protection of the TSH receptor binding sites in proportion to their derived TSH receptor occupancy. Receptor-bound bTSH was, therefore, able to protect the human TSH binding site from disulphide reduction. In addition, Graves' Ig, but not normal Ig, contained antibodies which were able to protect the TSH receptor binding sites in the same way as bTSH.(ABSTRACT TRUNCATED AT 250 WORDS)
An Approach to Ensuring Consistency in Peer-to-Peer Real-Time Group Editors

Real-time group editors allow distributed users to edit a shared document at the same time over a computer network. Operational transformation (OT) is a well accepted consistency control method in state-of-the-art group editors. Significant progress has been made in this field but there are still many open issues and research opportunities. In particular, established theoretic OT frameworks all require that OT algorithms be able to converge along arbitrary transformation paths. This property is desirable because group editors that implement such algorithms will not rely on a central component for achieving convergence. However, this has not been achieved in any published work to our knowledge. We analyze the root of this problem and propose a novel state difference based transformation (SDT) approach which ensures convergence in the presence of arbitrary transformation paths. Our approach is based on a novel consistency model that is more explicitly formulated than previously established models for proving correctness. SDT is the first and the only OT algorithm proved to converge in peer-to-peer group editors.
Bioethics and rural health: theorizing place, space, and subjects

Abstract The field of bioethics has been criticized for its universalizing tendencies, attributed in a large part to its foundations in moral philosophy and the level of abstraction of much bioethical discourse. Efforts to particularize bioethics have included the “turn toward casuistry”, the emergence of feminist and disability rights critiques of mainstream bioethics, and ethnographic contributions that examine the situatedness of ethical acts, practices, and meanings in local contexts. Such work introduces into bioethics dimensions of space, place, and time; nonetheless, these remain relatively unexplored as constitutive elements and/or influences of the phenomena of ethics discourse and ethics-related practices. Drawing from an ethnographic study of genetics in rural health, this paper presents a sociological discussion of space/time and bioethics through examination of rural health settings. Issues raised include intersections of spatial and power relations, socio-spatial gradients of expertise, and socio-spatial dimensions of ethics knowledge and practices within medical settings.
An examination of the Phascolosoma subgenera Antillesoma, Rueppellisoma and Satonus (Sipuncula)

Three of the subgenera in the sipunculan genus Phascolosoma are reviewed, based on examination of type material. The presumed difference between the subgenera Antillesoma and Rueppellisoma (number of retractor muscles) is shown to be invalid and the taxa are therefore synonymous. The 15 species are either considered junior synonyms of P. antillarum (eight), transferred to other species or genera (six), or considered incertae sedis (one). Phascolosoma antillarum is redescribed. Of the eight species in the subgenus Satonus, only P. pectinatum remains valid: the others are considered either to belong to other taxa (four) or to be incertae sedis (three).
Regulating a Risk-Averse Firm under Incomplete Information

We examine the optimal regulatory policy for a risk-averse …rm when the …rm is imperfectly informed about its e¢ ciency parameter for a project at the time of contracting. The …rm’s risk aversion shifts the optimal regulatory policy from a …xed-price contract to a
ON DEFINING COHERENCE AND INTEGRITY IN THE CURRICULUM

In the AAC report, Integrity in the College Curriculum: A Report to the Academic Community (1985), four terms are used frequently to convey a sense of desired excellence in postsecondary education. The terms are curricular coherence, curricular integration, curricular rigor and, lending the report its title, curricular integrity. Although the report's language implies meanings of these terms, its imprecision may lead to multiple interpretation by readers. Faculty who desire to implement curricular changes based on the AAC report, as well as institutional researchers who desire to assess such changes, will need to define these terms more precisely. It is my intent in this brief article to propose some useful definitions and to encourage others to disagree or to expand on these suggestions. My argument begins with the useful notion that a curriculum is an academic plan. Both the AAC report and the earlier NIE report Involvement in Learning (1984) imply that curriculum may mean either a collection of course descriptions or, ex post facto, the intended or serendipitous experiences that students have while in college. Rather, in my judgment, curriculum is an academic plan, constructed by the faculty and possibly other knowledgeable individuals. The curriculum resembles a "trip tik" designed to lead to a desired destination. Like the planned trip itinerary, the curriculum or academic plan contains a number of elements appropriate to the outcomes to be achieved. Such elements include objectives specifying concepts, behaviors, skills, and attitudes to be learned, an explicit connection of the objectives to the needs of society and of individual learners, some evidence that the plan anticipates the prior experiences and knowledge of the students, a set of instructional techniques and learning aids believed to help learners achieve the objectives, and a specification of roles and obligations for the teacher and the learner. Thus the itinerary may vary as a function of different sets of students and teachers, although all are headed for a similar destination. Most importantly (but currently lacking in some Research