cssi/SciSciGPT-SciSciNet huggingface dataset:
Insulin-like growth factor binding protein (IGFBP) substrate zymography. A new tool to identify and characterize IGFBP-degrading proteinases.

Insulin-like growth factor binding protein (IGFBP) degrading proteinase activities have been described in biological fluids and conditioned media from numerous cell lines. To identify and characterize IGFBP-degrading proteinases, our laboratory has developed IGFBP substrate zymography. Herein, we illustrate how IGFBP substrate zymography can be used both to identify candidate IGFBP-degrading proteinases and characterize their degradative capabilities. For this purpose, human matrix metalloproteinase-3 (MMP-3), a proteinase that degrades IGFBP-3 in human fibroblast cultures, was first electrophoresed through a polyacrylamide gel containing IGFBP-3 as substrate and then analyzed for its ability to degrade the substrate into immunoreactive fragments that were abssorbed onto a polyvinylidene difluoride membrane. IGFBP-3 substrate zymography was capable of detections as little as 20 ng of human MMP-3, demonstrating a sensitivity similar to casein substrate zymography. Using the zymogram as a template, MMP-3 was identified in a standard SDS-polyacrylamide gel run in parallel with the zymogram, and the corresponding area of the gel was excised. Electroelution of the gel slice yielded active MMP-3 when examined by casein substrate zymography. Furthermore, digestion of IGFBP-3 in solution by the electroeluted MMP-3 revealed the same fragmentation pattern of the binding protein as that produced by MMP-3, which had not been electroeluted. Together, these studies demonstrate that IGFBP substrate zymography can be a useful tool for both the identification and the characterization of IGFBP-degrading proteinases.
Resolving disputes over reservoir-river operation

The main objective of this work is to allocate water with acceptable quality from a reservoir-river system to different water users and to determine the maximum acceptable pollution load that each user discharges to the river. To achieve this, a bargaining model is developed based on a system dynamics approach, and it is compared with an alternative model based on the Nash bargaining theory. The quality of water released from the reservoir is assessed considering selective withdrawal schemes, obtained from schemes based on operating rules derived from an artificial neural network (ANN) and a K-nearest neighborhood (NN) model. A river water-quality simulation model is also linked with the two bargaining models. These models are then applied to the Karkheh reservoir-river system and using a 50-year monthly time series of qualitative and quantitative data of this system. Finally, the performance criteria for the results of the models are determined and compared. This study shows the significant value of the ...
Penalizing strategic preference manipulation in multi-agent decision making

We consider the problem of group decision making where the selection process is based upon a group preference function, obtained by an aggregation of the participating agents individual preference functions. We describe some methods for formulating the group preference from the individual preference functions. We note the possibility of the individual agents strategically manipulating the information they provide, so as to further their own goal of getting their most preferred alternative selected by the group. With this in mind, we suggest ways of modifying the formulation of the group decision functions to discourage strategic manipulation by the participating agents.
Complete heart block in nonfamilial hyperekplexia

An infant with nonfamilial hyperekplexia had multiple episodes of tonic spasms that mimicked tonic seizures. They were accompanied by complete heart block and apnea. These episodes did not correlate with electroencephalographic epileptiform changes and were partially responsive to clonazepam, valproic acid, and cardiac pacemaker. Sudden death in hyperekplexia may be related to complete heart block and apnea during seizurelike episodes.
EFFECTS OF VARIOUS HORMONAL CONDITIONS IN THE INTACT RAT ON THE SYNTHESIS OF SERUM CHOLINESTERASE11

ALTHOUGH the influence of hormones on metabolism has long been recognized, the in vivo effects of endocrine secretions on specific enzyme systems have received relatively little attention (Jensen and Tenenbaum, 1944). Only recently have endocrinologists and pharmacologists (Dempsey, 1946; Tainter et al., 1946) begun to examine hormone-enzyme relationships in their analysis of the mechanisms by which the well known terminal effects of endocrine activity are attained. The present series of papers attempts to explore this general problem, using as a starting point a sex difference observed in rats and mice with respect to an enzyme in the liver and serum.
Gas Turbine Vibration Limits: A Fundamental View

Test data are presented which describe the vibration response characteristic of a typical industrial gas turbine. Vibration limits are discussed and a set of “standard” limits used for a large family of industrial gas turbines is shown.Copyright © 1973 by ASME
Terminals of Single Ia Fibers: Distribution within a Pool of 300 Homonymous Motor Neurons

The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fibers (Ia) have been recorded with the aid of an averaging computer. These responses were used to map the distribution of the terminals of single fibers within the pool of 300 motoneurons of the medial gastrocnemius muscle. Twelve Ia fibers were studied in separate experiments. Monosynaptic excitatory postsynaptic potentials were found in 94 percent of the 77 motoneurons investigated. This finding indicates that each of the 300 motoneurons must receive afferent fibers from almost all of the spindles of the muscle it innervates.
Mechanical and Electrical Stimulation Induces Calcium-Sensitive Mechanical Properties of Myoblast Derived Engineered Fibers

Skeletal muscle loss, through injuries, myopathies, and interventional medicine, presents major challenges in physiological function and clinical interventions [1]. Autologous tissue transplantation necessitates tissue loss from the donor site, and autologous grafts do not attain the strength of the original tissue. Exogenous tissue grafting faces similar strength issues, as well as the added challenge of immunorejection [2,3]. In vitro skeletal muscle tissue engineering holds promise for addressing these issues. However, these tissues have not yet shown proper dynamic response when compared to physiological muscle [2]. Mechanical and electrical stimulation have shown promise in improving construct properties [4], but mainly limited to 2D and scaffold-based constructs.Copyright © 2013 by ASME
Miniature vibration isolation system for space applications: Phase II

In recent years, there has been a significant interest in, and move towards using highly sensitive, precision payloads on space vehicles. In order to perform tasks such as communicating at extremely high data rates between satellites using laser cross-links, or searching for new planets in distant solar systems using sparse aperture optical elements, a satellite bus and its payload must remain relatively motionless. The ability to hold a precision payload steady is complicated by disturbances from reaction wheels, control moment gyroscopes, solar array drives, stepper motors, and other devices. Because every satellite is essentially unique in its construction, isolating or damping unwanted vibrations usually requires a robust system over a wide bandwidth. The disadvantage of these systems is that they typically are not retrofittable and not tunable to changes in payload size or inertias. During the Phase I MVIS program, funded by AFRL and DARPA, a hybrid piezoelectric/D-strut isolator was built and tested to prove its viability for retroffitable insertion into sensitive payload attachments. A second phase of the program, which is jointly funded between AFRL and Honeywell, was started in November of 2002 to build a hexapod and the supporting interface electronics and do a flight demonstration of the technology. The MVIS-II program is a systems-level demonstration of the application of advanced smart materials and structures technology that will enable programmable and retrofittable vibration control of spacecraft precision payloads. This paper describes the simulations, overall test plan and product development status of the overall MVIS-II program as it approaches flight.
Unmodified versus Caustics- Impregnated Carbons for Control of Hydrogen Sulfide Emissions from Sewage Treatment Plants

Unmodified and caustic-impregnated carbons were compared as adsorbents for hydrogen sulfide in the North River Water Pollution Control Plant in New York City over a period of 2 years. The carbons were characterized using accelerated H2S breakthrough capacity tests, sorption of nitrogen, potentiometric titration, and thermal analysis. The accelerated laboratory tests indicate that the initial capacity of caustic-impregnated carbons exceeds that of unmodified carbon, but the nature of real-life challenge streams, particularly their lower H2S concentrations, nullifies this advantage. As the caustic content of the impregnated carbon is consumed, the situation reverses, and the unmodified carbon becomes more effective. When the concentration of H2S is low, the developed surface area and pore volume along with the affinity to retain water create a favorable environment for dissociative adsorption of hydrogen sulfide and its oxidation to elemental sulfur, S4+, and S6+. In the case of the caustic carbon, the cata...
A perceptual mapping procedure for analysis of proximity data to determine common and unique product-market structures

Traditional techniques of perceptual mapping hypothesize that products are differentiated in a common perceptual space of attributes. This paper suggests that each product is differentiated not only in a common perceptual space, but also a unique perceptual space consisting of as many dimensions as the number of products. It provides a model and estimation procedure based on alternating least squares for estimating the model parameters.
Measurement-free tests of a general state-space model of prototype learning

Abstract A general state-space model of prototype learning is formulated which is used to organize and relate several special cases such as Hintzman's (1986) multiple-trace model, Metcalfe-Eich's (1982) holographic model, and connectionistic models ( Knapp and Anderson, 1984 ; McClelland and Rumelhart, 1985 ). Three basic properties were defined in terms of this general model—linearity, time-invariance, and non-interference. An experiment was conducted using a prototype production task in which subjects were asked to produce a prototypic spectrum after observing a series of random spectral stimuli generated from a common chemical compound. “Measurement free” tests of linearity, originally developed by Krantz (1973) , were performed with few assumptions about internal features that subjects may use to encode the stimulus information. The properties of linearity and noninterference were reasonably well supported, but the property of time-invariance was violated in a complex manner. These results corroborate previous findings by Busemeyer and Myung (1988) using more general “measurement free” tests.
Adenovirus and minute virus of mice DNAs are localized at the nuclear periphery

The localization of adenovirus 2 (Ad2) and Minute Virus of Mice (MVM) DNAs was studied in situ in infected HeLa cell nuclei using fluorescent DNA probes and confocal microscopy. Ad2 DNA was found in multiple foci which were localized along the periphery of the infected cell nuclei. MVM DNA was found in HeLa cell nucleoli which are associated with the nuclear envelope, and when co-infected with Ad2 MVM DNA was compartmentalized to multiple foci which again were localized at the nuclear periphery. The data are discussed in terms of a model for the role of intranuclear compartmentalization in eukaryotic DNA structure and function.
Atomistic Insight on the Charging Energetics in Subnanometer Pore Supercapacitors

Electrodes featuring subnanometer pores are favorable to the capacitance and energy density of supercapacitors. However, there is an energy penalty to enter subnanometer pores as ions have to shed part of their solvation shell. The magnitude of such an energy penalty plays a key role in determining the accessibility and charging/discharging of these subnanometer pores. Here, we report on the atomistic simulation of Na+ and Cl− ions entering a polarizable slit pore with a center-to-center width of 0.82 nm. We show that the free energy penalty for these ions to enter the pore is less than 14 kJ/mol for both Na+ and Cl− ions. The surprisingly small energy penalty is caused by the van der Waals attractions between ions and pore walls, the image charge effects, the moderate (19−26%) dehydration of the ions inside the pore, and the strengthened interactions between ions and their hydration water molecules in the subnanometer pore. The results provide strong impetus for further developing nanoporous electrodes f...
Gender, Movement, and History: Social and Spatial Transformations in 20th Century Maradi, Niger

Analyses of gender and space have been brought short by our awareness of the sterility of the familiar public-private binary, our difficulty gaining purchase upon local spatial practices through feminist abstractions insisting upon the importance of global ‘location’, and our growing realization that women are often implicated in the very gender ideologies that constrain them. In this paper, focusing upon historical changes in Muslim women's access to and occupation of different kinds of space in the Sahelian city of Maradi, Niger, the author shifts attention away from the spaces themselves and towards women's active movement through and transformation of the spaces of the body, the home, and the city. Women define themselves, their social status, and their economic possibilities by acquiring and transforming what the author calls ‘internal spaces’ and by entering into previously inaccessible ‘external spaces’. More concretely, they locate themselves socially and economically through the decoration of the...
Empirical constraints on the salinity of the europan ocean and implications for a thin ice shell

Induced electrical currents within Europa inferred from Galileo spacecraft magnetometer instrument data have been interpreted as due to a salty europan ocean. Published compositional models for Europa's ocean, based on aqueous leaching of carbonaceous chondrites, range over five orders of magnitude in predicted magnesium sulfate concentrations. We combine the Galileo spacecraft magnetometer-derived oceanic conductivities and radio Doppler data-derived interior models with laboratory conductivity vs concentration data for both magnesium sulfate solutions and terrestrial seawater to determine empirically the range of salt concentrations permitted for Europa's ocean. Solutions for both a three-layer spherical model, and a five-layer half-space model, that satisfy current preferred best fits to magnetometer data imply high, near-saturation salt concentrations and require a europan ice shell of less than 15 km thick, with a best fit at 4 km ice thickness. Adding a conductive core and mantle has a negligible effect on the amplitude when ocean conductivities are greater than a few Siemens per meter. Similarly, we find that including a realistic ionosphere has a negligible effect. We examine the implications of these results for the subsurface habitability of Europa.
Distribution of Field Bindweed and Hedge Bindweed in the USA

A survey of weed specialists and herbaria was conducted by mail with telephone follow-up in 1994 and 1995 to determine the distribution, abundance, and economic importance of field bindweed (Convolvulus arvensis L) and hedge bindweed [Calystegia sepium (L.) R. Br.] (Convolvulaceae) in the continental USA. Field bindweed occurs at densities regarded as serious (greater than 1000 acres/county) in 957 counties, moderate (between 250 and 1000 acres/county) in 845 counties, and low (less than 250 acres/county) in 573 counties in 47 of the 48 contiguous states. Only Florida and the southern parts of states from South Carolina to Texas do not report its presence. Field bindweed infestations have increased since 1970 in several western states but have decreased in importance in most Great Plains states. Based on detailed crop loss data for 10 states containing 52% of the seriously infested counties, we estimated the value of crop losses due to field bindweed in the USA at more than $377 million/yr. Hedge bindweed occurs at densities regarded as serious in 101 counties, moderate in 1109 counties, and low in 553 counties in 43 states. Although not as widespread as field bindweed, hedge bindweed appears to have increased in abundance since 1969 and continues to be a localized problem in the midwestern and eastern USA.
Disturbance of salt marsh vegetation by wrack mats in Great Sippewissett Marsh.

To quantify disturbance to salt marsh vegetation, and to test the notion that disturbance and species richness are related, we studied disturbance of vegetation by 195 wrack mats that had become stranded over Great Sippewissett Marsh. The mats varied in area, thickness, residence time, and elevation of stranding. Mats that were large, that had residence times of 3–4 months, and were stranded at higher elevations produced the most damage, ranging from total eradication to a decrease in shoot density of underlying vegatation. Thickness had no effect. About 70% of mats caused no damage, and of those that did, damage was usually 50% or less of the area beneath the mat. Plant species were differentially distributed along the tidal excursion within the marsh, and there were more species (8–9) high in the intertidal range than lower (4–6 species). Vertical distribution of species, species richness, and rate of annual disturbance were not well correlated, although highest and lowest disturbance rates corresponded to highest and lowest species richness. Most of the increases in species richness, however, occurred over a very small range of disturbance, so narrow that it seemed unlikely that disturbance affected richness. It seems more likely that factors other than disturbance rate control vertical position of species in salt marshes. It also appears that the effect of disturbance by wrack is less important than has been claimed.
Transplacental Transfer of Hepatitis B Neutralizing Antibody during Pregnancy in an Animal Model: Implications for Newborn and Maternal Health

Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2–5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.
Emeritus professors: Correlates of professional activity in retirement II

Dorfman (1980b) investigated correlates of professional activity in retirement of professors at a major state university who continued to reside in their academic community during the entire year. This follow-up study extends that research to the total population of emeriti by including emeriti who left the University community after retirement and emeriti who continued to live in the University community for part of the year. Interviews were conducted with 113 University of Iowa emeritus professors. There was consistency between level of professional activity during the preretirement career and level of professional activity in retirement for the entire group, with “stayers” more consistent than “leavers.” Significant correlates of professional activity in retirement for the entire group included rated importance of consulting and University service, strength of ties to colleagues and professional organizations outside the University, contacts with former students, and perceived rapidity of changes in knowledge in respondents' fields. Multiple regression results showed that the strongest predictors of professional activity in retirement were level of professional activity during the preretirement career and strength of ties to professional organizations outside the University.
Students’ Conceptions of Congruency Through the Use of Dynamic Geometry Software

This paper describes students’ interactions with dynamic diagrams in the context of an American geometry class. Students used the dragging tool and the measuring tool in Cabri Geometry to make mathematical conjectures. The analysis, using the cK¢ model of conceptions, suggests that incorporating technology in mathematics classrooms enabled a measure-preserving conception of congruency with which students’ could shift focus from shapes to properties. Students also interacted with dynamic diagrams in a novel way, which we call the functional mode of interaction with diagrams, relating outputs and inputs that result when dragging a figure. Students’ participation in classroom interactions through discourse and through actions on diagrams provided evidence of learning using tools within dynamic geometry software.
A new representation for modeling biomass to commodity chemicals development for chemical process industry

Abstract A new representation combining network and stage-gate frameworks to study the impact of capital and research & development (R&D) decisions on the evolution of biomass to commodity chemicals system is presented. The network representation is used to universally express the interconnections between the processing technologies and to track the material flow among them. The stage-gate representation is used to express the discrete nature of technology maturity levels. The corresponding mixed-integer nonlinear program is developed and solved for a case study. In this case study, ethylene and propylene can be produced from naphtha and/or biomass. The results of the sensitivity analysis reveal that the raw material costs are the dominant factors that dictate the optimum investment decisions and production plan for this system.
Abstract 3225: Influence of localized vibration loading on bone targeting of bisphosphonate

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Targeting of bisphosphanate analog to specific skeletal sites is investigated by using localized vibration loading. Breast, lung, and prostate cancer cells metastasize frequently at bone resulting in debilitating pain, which is one of the major complications in majority of patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates apart from being a potent inhibitor of bone resorption, also provides pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Our continued efforts in investigating site-selective skeletal targeting of bisphosphonates are primarily to establish modes to overcome such drug-related side-effects. Non-invasive near-infrared (NIR) fluorescence imaging was used to monitor binding of NIR dye conjugated bisphosphonate (osteosense) to specific skeletal sites in response to localized vibration loading. Vibration loading, was performed on multiple sets of mice- subjecting them to vibration frequency of 70 Hz for five min (5 times/week) duration at the right thigh region. Osteosense and was injected intravenously after 21-day exercise regime. Both noninvasive and ex vivo imaging show significantly increased NIR signals at the right surface of the lumbar vertebrae. The unequivocal outcome in both the cohort studies, following the localized vibration loading confirms the role of direct high-frequency vibration stimulation in bisphosphonate targeting. Histochemical analysis of the bone and the muscle describe the mechanistic role in the targeted binding of the bisphosphonate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3225. doi:10.1158/1538-7445.AM2011-3225
Metabolism and transport of γ-carboxyglutamic acid

Abstract γ-Carboxyglutamic acid residues have been shown to be present in prothrombin, the other vitamin K-dependent clotting factors, and more recently in bone and kidney proteins. This amino acid is formed by a posttranslational vitamin K-dependent carboxylation of glutamyl residues in polypeptide precursors of these proteins. It has now been demonstrated that this amino acid, either in the free or peptide-bound form, it not metabolically degraded by the rat, but is quantitatively excreted in the urine. In nephrectomized rats, the tissue concentration of intravenously administered γ-carboxyglutamic acid is increased, but there is still no evidence of any oxidative metabolism of this amino acid. This amino acid is transported by kidney slices against a concentration gradient, but does not accumulate in liver, intestinal or brain tissues. Prelimininary data suggest that γ-carboxyglutamic acid may be concentrated by a carrier system from the utilized by other amino acids.
Homovanillic acid concentrations in brain, CSF and plasma as indicators of central dopamine function in primates.

In a large number (91) of vervet monkeys, correlation coefficients were determined between homovanillic acid (HVA) concentrations in four brain areas. Significant correlations existed between dorsal frontal cortex and orbital frontal cortex and between putamen and caudate nucleus. However, no significant correlations existed between either cortical area and the basal ganglia areas.
Activation of NF-κB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia

Objective The purpose of this study was to determine whether activation of NF-κB and expression of COX-2 are associated with neutrophil infiltration in systemic vascular tissue of women with preeclampsia. Study design Subcutaneous fat biopsies were obtained at cesarean section or abdominal surgery from preeclamptic women (n = 7), normal pregnant women (n = 6), and normal nonpregnant women (n = 5). Resistance-sized vessels (10 to 200 μm) in subcutaneous fat were evaluated using immunohistochemical staining for: (1) CD66b, a neutrophil antigen, (2) nuclear factor-κB (NF-κB), a transcription factor for genes of inflammation, and (3) cyclooxygenase-2 (COX-2), an inflammatory gene product. Results The percentage of vessels which showed staining for CD66b, NF-κB, and COX-2 was significantly greater for preeclamptic patients as compared to normal nonpregnant or normal pregnant patients. In preeclamptic patients, vessel staining for NF-κB and COX-2 was present in both endothelium and in vascular smooth muscle. Leukocytes in the lumen and adhered to endothelium also stained for NF-κB and COX-2. Activation of NF-κB and expression of COX-2 were coincident with neutrophil flattening and adherence to endothelium and infiltration into the intimal space. Conclusion These data demonstrate activation of NF-κB and expression of COX-2 in systemic vasculature of women with preeclampsia, and they demonstrate that this vascular inflammation is linked with neutrophil infiltration. Neutrophil release of toxic substances, such as reactive oxygen species, TNFα and thromboxane, could be responsible for vasoconstriction and vascular dysfunction. These data clearly place preeclampsia in the category of an inflammatory disease associated with immune dysfunction.
Molecular mechanisms of cardiac hypertrophy induced by toxicants

Cardiac hypertrophy is an end point of chronic cardiac toxicity from a number of toxicants. Doxorubicin, cocaine, acetaldehyde, monocrotaline, and azide are examples of these toxicants, which may induce hypertrophy by increasing oxidants, circulating levels of catecholamines, and hemodynamic load or by inducing hypoxia. We summarize here the major signal transduction pathways and common changes in gene expression found with the classical hypertrophy inducers angiotensin II, endothelin 1, and catecholamines. Activation of G-proteins, calcium signaling, phosphoinositide 3-kinase (PI3K), certain family members of protein kinase Cs (PKCs), and three branches of mitogen-activated protein kinases (MAPKs), i.e. extracellular signal-regulated kinases (ERKs), p38, and c-Jun N-terminal kinases (JNKs), are important for developing a hypertrophic phenotype in cardiomyocytes. Characteristic changes of gene expression in hypertrophy include the elevated transcription of atrial natriuretic factor (ANF), β-myosin heavy chain (βMHC), skeletal α-actin (SkA), certain variants of integrins and perhaps tubulin genes, and reduced expression of the sarcoplasmic reticulum proteins phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPase 2α (SERCA2α), and of the ryanodine receptors. Although which toxicants induce these molecular changes remains to be tested, increasing lines of evidence support that oxidants play a central role in cardiac hypertrophy. Oxidants activate small G-proteins, calcium signaling, P13K, PKCs, and MAPKs. Oxidants cause cardiomyocytes to enlarge in vitro. Recent developments in transgenic, genomic, and proteomic technologies will provide needed tools to reveal the mechanism of chronic cardiac toxicity at the cellular and molecular levels.
Rearrangements of Nascent Peptide Inside the Ribosomal Exit Tunnel

All proteins, from bacteria to man, are made in the ribosome and are elongated, one residue at a time, at the peptidyl transferase center (PTC). This growing peptide chain wends its way through the ribosomal tunnel to the exit port, ∼ 100 angstroms from the PTC. Regulation of the movement of the peptide within the tunnel and allosteric communication along the tunnel during translation are not well understood. Previously, we demonstrated that solvent-accessible volume surrounding a modifiable cysteine increases monotonically with increase in the van der Waal's volume of the adjacent side chain (Lu et al., J.Mol.Biol. 411: 499-510, 2011) and that the magnitude of this effect depends on location within the ribosomal tunnel. using a photocrosslinking approach, we confirm these results. We extend these studies to investigate whether mutations in the nascent peptide deep in the tunnel affect the accessibility of a modifiable reporter cysteine at the exit port and whether specific regions of the tunnel instigate these effects. Tryptophan vis-a-vis alanine, engineered into the nascent peptide at a distance of 17-19 residues from the PTC, alters the accessibility of residues at the exit port, a distance of 33 residues from the PTC, roughly 50 angstroms from the introduced point mutations. These findings are consistent with long-range rearrangements and may contribute to mechanisms governing sequence-specific signaling from different regions of the tunnel during translation. Supported by NIH grant R01GM52302.
A phase II study of gefitinib in patients with advanced thyroid cancer.

Objective: To determine the efficacy of gefitinib in patients with advanced thyroid cancer. Design: In this open-label phase II trial, 27 patients with radioiodine-refractory, locally advanced, or metastatic thyroid cancer were treated with 250 mg of daily gefitinib. Histologic subtypes included papillary (41%), follicular (22%), anaplastic (19%), medullary (15%), and Hurthle cell carcinomas (4%). The primary endpoint was overall response rate. Secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). Main outcomes: There were no objective responses among the 25 patients evaluated. After 3, 6, and 12 months of treatment, 48%, 24%, and 12% of patients had stable disease (SD), respectively. Median PFS and OS were 3.7 and 17.5 months, respectively. Five patients with SD had a decrease in thyroglobulin (Tg) to <90% of baseline that was maintained for at least 3 months. Conclusions: Although gefitinib therapy did not result in any tumor responses, 32% of patients had reduct...
A High-Throughput Processor for Flight Control Research Using Small UAVs

There are numerous autopilot systems that are commercially available for small (<100 lbs) UAVs. However, they all share several key disadvantages for conducting aerodynamic research, chief amongst which is the fact that most utilize older, slower, 8- or 16-bit microcontroller technologies. This paper describes the development and testing of a flight control system (FCS) for small UAV s based on a modern, high throughput, embedded processor. In addition, this FCS platform contains user-configurable hardware resources in the form of a Field Programmable Gate Array (FPGA) that can be used to implement custom, application-specific hardware. This hardware can be used to off-load routine tasks such as sensor data collection, from the FCS processor thereby further increasing the computational throughput of the system.
The advent of chemical symbolism in the art of Sonya Rapoport

This paper explores the use of chemical symbolism in works by the new media artist Sonya Rapoport, with a focus on the pivotal Cobalt series from the late 1970s. These works, drawings on computer printouts generated by research at the Lawrence Berkeley Laboratory, respond to experiments in nuclear chemistry. They mark the beginning of three productive decades in which Rapoport produced a variety of images related to chemistry in her work. She states, “I looked for authentic research projects that were interesting to me, preferably with captivating pictorial subject matter. Then came the creative chaotic process of resolving a cohesive product that combined scientific research with art concept.” Rapoport had an unusual degree of access to scientific materials through her husband, organic chemist Henry Rapoport, a faculty member at the University of California, Berkeley. At the time of production, these works were outside mainstream art world interests and they have received little critical attention. This paper examines the development of Rapoport’s images and places her use of chemical references in context in her lifetime of work.
Moral leadership in schools

The genesis of the moral leadership concept in educational administration and examples of studies exploring this idea during the 1979‐2003 period are discussed. The author recommends more contextually sensitive descriptive studies with a focus on the social relations among school leaders and others, giving particular attention, in a phenomenological sense, to the meanings, perspectives, and espoused purposes of school leaders’ actions, social relationships, and interpersonal orientations.
Detection of a D″ discontinuity in the south Atlantic using PKKP

[1] A strong arrival in the early coda of major-arc PKKPab is observed on recordings of earthquakes in the Banda Sea region from the short-period, small-aperture Yellowknife array. The arrival has a move-out close to PKKPab with an average delay of ∼12 s. We show that the phase is most likely an underside reflection from a D″ discontinuity above the PKKP reflection point at the core-mantle boundary beneath the southern Atlantic on the edge of the African superplume. Differential travel times between PKKPab and PKdKP (the underside reflection at the D″ discontinuity) is used to constrain potential D″ velocity models. The high amplitude of PKdKP requires proximity to the b-caustic adding further velocity control. We find that a P-velocity model with a sharp positive velocity jump ∼280 km above the core-mantle boundary, and a negative velocity gradient closer to the core-mantle boundary, fits the data well.
Success Profiles for Student Examination Performance in a Large-Lecture Management Course: An Empirical Study

Two studies of student performance on multiple-choice examinations in a large-lecture introductory management course are reported. Study 1 used focus groups to isolate potentially meaningful patterns differentiating high and low performers. Study 2 used discriminant analysis to further examine these patterns. Results indicate that students' undergraduate majors, selected study habits, process variables, and learning styles all make a difference in their examination performance. The findings regarding study habits suggest a number of specific guidelines to help students better prepare for large-lecture multiple-choice examinations. The findings overall raise a number of additional questions worthy of further research and instructional consideration.
Mondragon: Adapting Co-operative Structures to Meet the Demands of a Changing Environment

The Mondrag6n co-operatives of the Basque region of northern Spain are currently adapting to changing market conditions in Europe, pursuing a strategy of scale within priority sectors. This article...
A 5-GHz Mesh Interconnect for a Teraflops Processor

A multicore processor in 65-Nm technology with 80 single-precision, floatingpoint cores delivers performance in excess of a Teraflops while consuming less than 100 W. A 2D on-die mesh interconnection network operating at 5 GHz provides the high-performance communication fabric to connect the cores. The network delivers a bisection bandwidth of 2.56 Terabits per second and a per hop fall-through latency of 1 nanosecond.
Decisions to limit life-sustaining treatment for critically ill patients who lack both decision-making capacity and surrogate decision-makers.

Objective:Many intensive care unit (ICU) physicians have withdrawn life-support from a patient who lacked decision-making capacity and a surrogate decision-maker, yet little is known about the decision-making practices for these patients. We sought to determine how often such patients are admitted t
Cosmic Rays and the Sun's Magnetic Field: Diurnal Variation of Cosmic Rays and the Sun's Magnetic Field

Cosmic Rays and the Sun's Magnetic Field: Diurnal Variation of Cosmic Rays and the Sun's Magnetic Field
Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation.

The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b’s adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b−/− progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b’s absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.
Unsolved Problems in Photobiology

Photobiology has been broadly defined to include all biological phenomena involving nonionizing radiation. It is recognized that photobiological responses are the result of chemical and/or physical changes induced in biological systems by nonionizing radiation.
Growth-inhibitory effects of a mineralized extract from the red marine algae, Lithothamnion calcareum, on Ca2+-sensitive and Ca2+-resistant human colon carcinoma cells

Proliferation and differentiation were assessed in a series of human colon carcinoma cell lines in response to a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum. The extract contains 12% Ca2+, 1% Mg2+, and detectable amounts of 72 trace elements, but essentially no organic material. The red algae extract was as effective as inorganic Ca2+ alone in suppressing growth and inducing differentiation of colon carcinoma cells that are responsive to a physiological level of extracellular Ca2+ (1.4 mM). However, with cells that are resistant to Ca2+ alone, the extract was still able to reduce proliferation and stimulate differentiation.
Regulation of renin release via cyclic ADP-ribose-mediated signaling: evidence from mice lacking CD38 gene.

Background/Aims: Despite extensive studies, the intracellular regulatory mechanism of renin production and release is still poorly understood. The present study was designed to test whether CD38-ADP-ribosylcyclase signaling pathway contributes to the regulation of renin production and release, and to examine whether CD38 gene knockout (CD38 -/- ) can change this important renal endocrinal function. Methods: ADP–ribosylcyclase activity was estimated utilizing HPLC, cADPR levels from western blot, plasma renin activity from RIA kit, urinary sodium and potassium excretion from flame photometry. Results: The expression of CD38 and the activity of ADP-ribosylcyclase to produce cyclic ADP-ribose (cADPR) were nearly abolished in the kidney from CD38 -/- mice, indicating that CD38 gene is a major enzyme responsible for the generation of cADPR in vivo. Mice lacking CD38 gene showed increased plasma renin activity (PRA) in either conscious or anesthetized status (P<0.05). Low salt intake significantly increased, but high salt intake significantly decreased renin release in both CD38 +/+ and CD38 -/- mice. In acute experiments, it was demonstrated that plasma renin activity (PRA) significantly increased upon isoprenaline infusion in CD38 -/- mice compared to CD38 +/+ mice. Accompanied with such increase in PRA, glomerular filtration rate (GFR), renal blood flow (RBF), urine volume (UV) and sodium excretion (U Na V) more significantly decreased in CD38 -/- than CD38 +/+ mice. Similarly, more increases in PRA but more decreases in GFR, RBF, UV and U Na V were observed in CD38 -/- than CD38 +/+ mice when they had a low renal perfusion pressure (RPP). Conclusion: CD38-cADPR-mediated signaling may importantly contribute to the maintenance of low PRA and participate in the regulation of renal hemodynamics and excretory function in mice.
Impact of the Leapfrog Group's intensive care unit physician staffing standard.

Abstract Purpose The aim of this study was to describe hospital efforts to meet the Leapfrog Group's intensive care unit (ICU) physician staffing (IPS) standard; compare adopters and committers with resisters relative to perceived benefits, barriers and motivating factors; and examine implementation strategies. Materials and methods Chief medical officers (CMO) and ICU directors at hospitals in 6 US regions were surveyed between August 2003 and January 2004. Hospital classifications were based on level of IPS implementation pioneer (met before IPS), adopter (met after IPS by 2002 Leapfrog survey), committer (not met but committed to December 2004 implementation), and resister (refused to adopt IPS). Meeting IPS included intensivist staffing, 8 hours/day 7 days/week; sole patient care in ICU; 95% pager response time ≤5 minutes; and physicians certified in critical care. Results Forty-three (80%) CMOs and 42 (78%) ICU directors were interviewed. Adopters (100%), committers (80%), and resisters (45%) employed intensivists; 1 adopter (14%) met all criteria for standard. Main motivators for implementation were “quality of patient care” for CMO (79%) and ICU director (71%) adopter/committers. Incentives to implement were increasing intensivist authority (90% committers) and intensivist salary support (80% committers and 70% adopters). Main resister barriers were implementation costs (61% CMOs) and medical staff controversy (55% ICU directors). Conclusion Most hospitals—including half of those who publicly resisted the standard—made attempts to change physician staffing in their ICUs, based on the criteria outlined by the Leapfrog Group. Major barriers that need addressing are implementation costs and convincing hospital organizations and medical staff regarding the benefits of adopting the standard.
Reconstruction in emission tomography via a Bayesian multiscale statistical framework

Recently the authors introduced a general Bayesian statistical method for modeling and analysis in linear inverse problems involving certain types of count data. Emission-based tomography is medical imaging is a particularly important and common examples of this type of proem. In this paper we provide an overview of the methodology and illustrate its application to problems in emission tomography through a series of simulated and real- data examples. The framework rests on the special manner in which a multiscale representation of recursive dyadic partitions interacts with the statistical likelihood of data with Poisson noise characteristics. In particular, the likelihood function permits a factorization, with respect to location-scale indexing, analogous to the manner in which, say, an arbitrary signal allows a wavelet transform. Recovery of an object from tomographic data is the posed as a problem involving the statistical estimation of a multiscale parameter vector. A type of statistical shrinkage estimation is used, induced by careful choice of a Bayesian prior probability structure for the parameters. Finally, the ill-posedness of the tomographic imaging problem is accounted for by embedding the above-described framework within a larger, but simpler statistical algorithm problem, via the so-called Expectation-Maximization approach. The resulting image reconstruction algorithm is iterative in nature, entailing the calculation of two closed-form algebraic expression at each iteration. Convergence of the algorithm to a unique solution, under appropriate choice of Bayesian prior, can be assured.
Effect of Maternal Asthma on Performance of Parenting Tasks and Children's School Attendance

We evaluated the effects of maternal asthma on specific parameters of family function including the children's school attendance and mother's performance of basic parenting tasks. A case-controlled study of mothers with asthma (MA; n = 24) with children under the age of 13 and matched mothers without asthma (CM; n = 27) was performed. Children of mothers with asthma had a significantly impaired ability to attend school compared to children of control mothers (odds ratio = 15,95% CI). Twenty-two percent of MA reported that their asthma caused their children to miss school at least once per month. In addition, 27% of MA reported that their children were regularly late for school because of the mother's asthma. Only 5% of the control mothers reported that their health caused their children to miss school, and none reported lateness. Asthma also impaired the ability of the MA to perform basic parenting tasks such as dressing children and preparing meals for children. These adverse effects of parental asthma o...