cssi/SciSciGPT-SciSciNet huggingface dataset:
Contributions of Remodeling and Asymmetrical Growth to Vertebral Wedging in a Scoliosis Model.

Abstract Study Design We performed a laboratory study of rats of 3 different ages with imposed angulation and compressive loading to caudal vertebrae to determine causes of vertebral wedging. Objectives The purpose was to determine the percentage of total vertebral wedging that was caused by asymmetric growth, vertebral body, and epiphyseal wedging. Approval from the Institutional Animal Care and Use Committee, the University of Vermont, was obtained for the live animal procedures used in this study. Background Summary Vertebral wedging from asymmetrical growth (Hueter-Volkmann law) is reported to cause vertebral wedging in scoliosis with little attention to the possible contribution of bony remodeling (Wolff’s law). Methods In our study, an external fixator imposed a 30° lateral curvature and compression of 0.1 megapascal (MPa) in 5- and 14-week-old animals (Groups 1 and 2) and 0.2 MPa in 14- and 32-week-old animals (groups 3 and 4). Total vertebral wedging was measured from micro CT scans. Wedging due to asymmetrical growth and epiphyseal remodeling was calculated from fluorescent labels and the difference was attributed to vertebral body wedging. Results Total vertebral wedging averaged 18°, 6°, 10° and 5° in Groups 1, 2, 3, and 4, respectively. Metaphyseal asymmetrical growth averaged 8°, 1°, 4°, 0° (44%, 17%, 40% and 0% of total). Epiphyseal wedging averaged 9°, 0°, 3°, and -1°. The difference (vertebral body) averaged 1°, 5°, 3°, and 7° (6%, 83%, 30% and 140% of total). The growth of the loaded vertebrae as a percentage of control vertebrae was 56%, 39% and 25% in Groups 1, 2 and 3; negligible in Group 4. Vertebral body cortical remodeling, with increased thickness and increased curvature on the concave side was evident in young animals and 0.2 MPa loaded older animals. Conclusions We conclude that asymmetrical growth was the largest contributor to vertebral wedging in young animals; vertebral body remodeling was the largest contributor in older animals. If, conversely, vertebral wedging can be corrected by appropriate loading in young and old animals, it has important implications for the nonfusion treatment of scoliosis.
COMPOSITION OF THE LIPIDS OF CUCUMBER AND PEPPERS

SUMMARY— Cucumber and green peppers contain 103 mg and 400 mg total lipid per 100g raw vegetable tissue. The neutral lipids, phospholipids and glycolipids comprise 39, 49 and 15% of the cucumber lipids and 82, 2 and 16% of the pepper lipids respectively. The neutral lipids of both were composed mainly of glycerides. In the peppers the triglycerides accounted for 60% of the total lipids. Cucumber, had less glycerides but contained several unidentified sterols. Phosphatidylcholine was the major class in both vegetables accounting for 46 and 76% of the phospholipids of cucumber and pepper respectively. Palmitic, linoleic and linolenic acids were the principal fatty acid components. The lipids of peppers were very rich in linoleic acid (70%) whereas those of the cucumbers contained relatively more linolenic acid.
Genetic mapping and manipulation: chapter 2--Two-point mapping with genetic markers.

Copyright: © 2006 David Fay. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. To whom correspondence should be addressed. E-mail: davidfay@uwyo.edu Genetic mapping and manipulation: Chapter 3-Three-point mapping with genetic markers* David Fay, Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071-3944 USA
CORRELATION ENERGY OF THE TWO-ELECTRON ATOM IN A SPHERICAL POTENTIAL BOX.

Results of calculations approximating the electronic Coulomb correlation energy of the two‐electron atom in a spherical potential box are reported and discussed. Although the total electronic energy of such an atom varies rather widely with changes in the radius of the box, the correlation energy seems to be relatively insensitive to such changes except for box radii on the order of or smaller than the atomic radius.
Word and pseudoword superiority effects reflected in the ERP waveform

A variant of the Reicher-Wheeler task was used to determine when in the event-related potential (ERP) waveform indices of word and pseudoword superiority effects might be present, and whether ERP measures of superiority effects correlated with standardized behavioral measures of orthographic fluency and single word reading. ERPs were recorded to briefly presented, masked letter strings that included real words (DARK/PARK), pseudowords (DARL/PARL), nonwords (RDKA/RPKA), and letter-in-xs (DXXX, PXXX) stimuli. Participants decided which of two letters occurred at a given position in the string (here, forced-choice alternatives D and P). Behaviorally, both word (more accurate choices for letters in words than in baseline nonwords or letter-in-xs) and pseudoword (more accurate choices for letters in pseudowords than in baseline conditions) superiority effects were observed. Electrophysiologically, effects of orthographic regularity and familiarity were apparent as early as the P150 time window (100-160 ms), an effect of lexicality was observed as early as the N200 time window (160-200 ms), and peak amplitude of the N300 and N400 also differentiated word and pseudoword as compared to baseline stimuli. Further, the size of the P150 and N400 ERP word superiority effects was related to standardized behavioral measures of fluency and reading. Results suggest that orthographic fluency is reflected in both lower-level, sublexical, perceptual processing and higher-level, lexical processing in fluently reading adults.
Associations among Calcium Intake, Resting Energy Expenditure, and Body Fat in a Multiethnic Sample of Children

Objective The objective was to determine if calcium intake was associated with resting energy expenditure (REE) and body fat in children after accounting for ancestral genetic background. Study design Participants included 315 children. REE, body composition, and dietary calcium were assessed by indirect calorimetry, dual-energy x-ray absorptiometry, and 24-hour recalls, respectively. Structural equations modeling assessed the relationships among REE, calcium intake, and body fat. Results There were positive associations between calcium intake and REE (P < .01) and between REE and total body fat (P < .0001). There was indirect effect of calcium intake on total body fat (P < .01). There were positive associations between calcium intake and REE (P < .01), and a trend toward an association of calcium intake and total body fat (P = .065) among boys only, whereas the only significant relationship among girls was an association of REE on total body fat (P < .0001). Conclusions REE was associated with calcium intake and mediated a relationship between calcium intake and total body fat. These findings suggest calcium intake may play a role in fat accumulation and energy balance through its effects on REE, especially in boys. (J Pediatr 2010;157:473-8).
Learning from others, reacting, and market quality

Abstract Traders pay attention to one another but are unable to perfectly deduce each others’ beliefs from transactions alone. This explains why markets are hard to beat and also why trading occurs at all. Even when traders react rationally to the actions of others, they cannot arrive easily at a common posterior assessment of value. We model a realistic market composed of traders who combine their own private information with rational learning about the information possessed by others. We compare phenomena in this market with an otherwise identical market populated by traders who receive the same private information but ignore other traders. Using simulation to engender greater realism, we find that learning usually reduces volatility, increases the accuracy of the market price as a forecast of value, reduces trading volume, and decreases the prevalence of bubbles. However, for some combinations of market conditions, learning can have the opposite effect. The marginal influences of eight different market conditions, ranging from information heterogeneity through resource diversity, are estimated. Prices, volatility, volume, and bubbles exhibit subtle and complex responses to market conditions.
Fatigue damage prediction of cruciform specimen under biaxial loading

This article investigates an energy-based multiscale damage criterion for a biaxial loading case. The criterion incorporates crystal plasticity at the microscale that produces a damage tensor, representing the local damage state derived from a least squares method. The damage tensor, driven by modification of strain energy density on each potential slip system, is averaged from local to grain level to obtain a damage vector for each grain. The Kreisselmeier–Steinhauser function, which produces an envelope function for multiobjective optimization is adopted to predict the failure of a meso–representative volume element, and to calculate the damage index for meso–representative volume element. A weighted averaging method is also used to simultaneously provide the most potential cracking directions for meso–representative volume element. In order to verify that the developed method is capable of producing an acceptable prediction of fatigue damage initiation and growth under multiaxial loading conditions, a ...
Isothermal mass flow measurements in microfabricated rectangular channels over a very wide Knudsen range

Measurement and modeling of gas flows in microelectromechanical systems (MEMS) scale channels are relevant to the fundamentals of rarefied gas dynamics (RGD) and the practical design of MEMS-based flow systems and micropumps. We describe techniques for building robust, leak-free, rectangular microchannels which are relevant to micro- and nanofluidic devices, while the channels themselves are useful for fundamental RGD studies. For the first time, we report the isothermal steady flow of helium (He) gas through these channels from the continuum to the free-molecular regime in the unprecedented Knudsen range of 0.03–1000. On the high end, our value is 20-fold larger than values previously reported by Ewart et al (2007 J. Fluid Mech. 584 337–56). We accomplished this through a dual-tank accumulation technique which enabled the monitoring of very low flow rates, below 10−14 kg s−1. The devices were prebaked under vacuum for 24 h at 100 °C in order to reduce outgassing and attain high Kn. We devised fabrication methods for controlled-depth micro-gap channels using silicon for both channel ceiling and floor, thereby allowing direct comparisons to models which utilize this simplifying assumption. We evaluated the results against a closed-form expression that accurately reproduces the continuum, slip, transition, and free-molecular regimes developed partly by using the direct simulation Monte Carlo method. The observed data were in good agreement with the expression. For Kn > ~100, we observed minor deviations between modeled and experimental flow values. Our fabrication processes and experimental data are useful to fundamental RGD studies and future MEMS microflow devices with respect to extremely low-flow measurements, model validation, and predicting optimal designs.
Efficacy of interferon-γ and amphotericin B for the treatment of systemic murine histoplasmosis

Abstract The number of cases of systemic histoplasmosis has increased substantially in recent years, and improved therapy is needed. We examined the efficacy of immunomodulation with interferon (IFN)-γ alone or in combination with a suboptimal regimen of amphotericin B for the treatment of primary systemic murine histoplasmosis. In the first study, BALB/c mice were infected with Histoplasma capsulatum G217B and treated with 105 U of IFN given every other day either preinfection and postinfection or only postinfection, alone or in combination with amphotericin B. IFN alone given subcutaneously (s.c.) postinfection prolonged survival over untreated controls (P
A REPLY TO HELEN SPEIGHT

I530s, as set out in the thoughtful essay above, offers an alternative to my own and to Professor Elton's, and is shaped by the 'county community' school of historians who have in the past three decades added much to our knowledge of the nature, composition and attitudes of the local governing classes. From this 'provincial rather than a court-based vantage point' [Speight p. 638], the importance of events, individuals and local affairs appears quite different than it would to a central government of king, court and Thomas Cromwell; our differing interpretations present an interesting illustration of the degree to which an historian's interests may inform her conclusions. As it happens, the foundations of both arguments occupy a good deal of common ground. We agree that government in the southwest, as elsewhere in England, depended on the co-operation of the ruling gentry elites who traditionally monopolized local offices; that there was reform in the government of the provinces of the Tudor state during the sixteenth century [Speight p. 638]; that 'Cromwell took a particularly active interest in local government and showed an acute awareness of its importance' [Speight p. 637]; that he influenced the appointments of some western sheriffs, but did not try to pack the commissions of the peace, the composition of which exhibited a remarkable continuity throughout the period (the argument that he was influential in
The Guitar nebula - A bow shock from a slow-spin, high-velocity neutron star

The discovery is reported of a prominent nebula produced by the motion of a high-velocity pulsar, PSR 2224 + 65, through partially neutral gas. The pulsar's transverse speed of over about 800 km/s makes it arguably the fastest known star in the Galaxy and guarantees that it will ultimately escape the Galactic potential well. A deep H-alpha image reveals a bright head and a giant limb-brightened 'body' whose variable width suggests that the ambient interstellar gas has density variations on length scales less than 0.1 pc. Thermalization of shock energy occurs at a rate of about 0.01 times the pulsar's spindown loss rate. These observations provide some insights into the likelihood of finding shocks around other pulsars and the use of nebulae to find high-velocity neutron stars either not acting as pulsars or with their radiation beamed away from the earth.
Widespread but Small-Scale Changes in the Structural and Dynamic Properties of Vaccinia Virus Poly(A) Polymerase upon Association with Its Processivity Factor in Solution

Vaccinia virus poly(A) polymerase (VP55) has been analyzed via hydrogen−deuterium exchange (HDX) mass spectrometry in the absence and presence of its processivity factor, VP39, to improve our understanding of the mechanism by which processivity is impressed on the polymerase. For 119 peptic peptides covering 74.1% of VP55, the extent of HDX at 900 s was interpreted in the context of parameters deduced from the VP55−VP39 X-ray crystal structure. While HDX exhibited a degree of correlation with the mean SASA of whole residues within each peptide segment, HDX was generally more active than expected from either the SASA or hydrogen bonding status of the exchangeable amide proton, indicating a significant molecular dynamics contribution to amide proton deprotection. Peptic peptides undergoing either more or less HDX than expected were distributed throughout VP55 and showed consistency between multiple overlapping peptides. VP39 had a net, marginal cooling effect on VP55, indicating a possible restriction of VP...
Just-in-Time: Performance and the Aesthetics of Precarity

Integrating post-Operaismo social theory with recent turns in performance studies shows how such theory complicates and is complicated by cross-arts questions around virtuosity and affective labor. Such complications emerge, not only in the contemporary art sphere, but also in the history and theory developed by performance studies as a discipline.
Geochemical evidence for invasion of Kilauea's plumbing system by Mauna Loa magma

From the beginning of the study of Hawaiian volcanism there has been controversy over possible relationships between the neighbouring active volcanoes Mauna Loa and Kilauea1–5. Seismic activity, thought to reflect upward migration of magma, reveals that the magmatic plumbing systems apparently converge at depth to form a broad funnel within the mantle6. Although on rare occasions they have erupted concurrently, the brief historical eruptive record appears to show that when Kilauea is most active, Mauna Loa is in repose and vice versa, suggesting that they may be competing for the same magma supply5,7. Petrological, geochemical and isotope data, however, require a diametrically opposite conclusion. Distinct differences in major-element, trace-element and isotope compositions of lavas are regarded as compelling evidence that the two volcanoes have separate magmatic plumbing systems, supplied by parental magmas from physically and geochemically distinct mantle sources8–13. Here we present preliminary geochemical data which show that in the past 2,000 years Kilauea has erupted a spectrum of lava compositions resembling historical Kilauea lavas at one end and Mauna Loa lavas at the other. We discuss the cause of this diversity, and speculate that magma from Mauna Loa may have invaded Kilauea's 'high-level' magmatic plumbing system.
Scale-invariant shape representation based on the wavelet transform

Matching of occluded objects is a difficult problem. Moreover, the problem is more difficult when scale-invariant matching is needed. A scale invariant representation is essential for this application. In this paper, we propose using the wavelet transform of a boundary to obtain a scale-invariant representation. We use the cubic B-spline as a smoothing function of the wavelet transform since the B-spline is analytically well defined and simple to implement. We implement the fast continuous wavelet transform by using a dyadic wavelet decomposition and dilated B-splines. As a result of using the wavelet transform, we obtain boundaries at various scales while using a small number of data points. The existing scale-space image approaches are not effective for occluded object matching since they use a normalized x-axis and too many data points. We propose a new scale-invariant representation similar to the scale-space image. The representation is generated by locating zero-crossings of the curvature function of boundaries at only the scales where the number of zero-crossings is changing. We scale the x-axis for each scale instead of using the same normalization for all scales. The proposed representation is scale-invariant and appropriate for scale-invariant matching with occlusion.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Comparisons of price and quantity controls: A survey

Abstract The recent comparisons of price and quantity controls under uncertainty are reviewed with an eye toward discovering their unifying concepts. From the original comparison conducted by Weitzman through the more sophisticated studies of multiple producers, multiple goods, intermediate goods, and pollution, output variation emerges as that unifying link. When the control choice is important, the control that creates the better distribution of outputs in terms of magnitude and of correlation with the stochastic elements of the social loss function is preferred.
Tolerance to methadone lethality and microsomal enzyme induction in mice tolerant to and dependent on morphine

Abstract In an attempt to explain a loss of cross-tolerance between morphine and methadone and an increased tolerance to methadone lethality in morphine-dependent mice administered methadone orally for six days, the possibility that methadone was stimulating its own metabolism was investigated. It was found that methadone did enhance its own metabolism two-fold. This increase in activity correlated with the development of tolerance to the lethal effects of methadone as measured by an elevation of the oral methadone LD 50 . Furthermore, SKF-525A, a potent microsomal inhibitor, abolished this tolerance. The intracerebroventricular methadone LD 50 was not altered by six days administration of oral methadone, suggesting that the tolerance observed was dispositional in nature.
Mutational analysis of ATP-grasp residues in the two ATP sites of Saccharomyces cerevisiae carbamoyl phosphate synthetase.

Abstract The ATP-grasp fold is found in enzymes that catalyze the formation of an amide bond and occurs twice in carbamoyl phosphate synthetase. We have used site-directed mutagenesis to further define the relationship of these ATP folds to the ATP-grasp family and to probe for distinctions between the two ATP sites. Mutations at D265 and D810 severely diminished activity, consistent with consensus ATP-grasp roles of facilitating the transfer of the γ-phosphate group of ATP. H262N was inactive whereas H807N, the corresponding mutation in the second ATP domain, exhibited robust activity, suggesting that these residues were not involved in the ATP-grasp function common to both domains. Mutations at I316 were somewhat catalytically impaired and were structurally unstable, consistent with a consensus role of interaction with the adenine and/or ribose moiety of ATP. L229G was too unstable to be purified and characterized. S228A showed essentially wild-type behavior.
Drugs for Severe Chronic Pain

Excerpt To the editor: The treatment of pain is one of the most troublesome and least understood aspects of the care of terminally ill patients. I was therefore pleased to see the American College ...
Widely tunable diode lasers for WDM applications

Summary form only given. As dense-WDM architectures become pervasive in long-haul, metropolitan and local-area fiber-optic networks, the desire to have lasers that emit at any of several hundred ITU-grid wavelengths from a single waveguide increases. Applications include use in programmable WDM source modules, wavelength converter modules, and opaque optical switches. This tutorial reviews a number of promising widely tunable (>30 nm @ 1550 nm) laser technologies and attempt to outline some of their attributes.
Evolutionary and phylogenetic relationships of rubredoxin-containing microbes.

Abstract The primary structure of the Pseudomonas oleovorans rubredoxin, except for the placement of several residues, is presented. There is evidence for gene duplication in the Pseudomonas oleovorans rubredoxin. When the primary structures of this rubredoxin and the rubredoxins from anaerobic bacteria were compared, homologous sequences were observed. The best homology was obtained by creating an ancestral sequence and then comparing each of the rubredoxins with the ancestral sequence. This had led to the theory that proposed that all of the three rubredoxins have arisen from a common ancestor. A phylogenetic tree based on the primary structure data is presented.
Multi-Level Converters

In the history of modern power electronics evolution, we are now going through the era of multi-level converters [1]. [...]
A simulation model of port operations during crisis conditions

We consider the supply chain for containerized items that arrive at a port in the U. S. whose final destination is also in the U. S. Ports are important entities in global supply chains. As such, when a port cannot operate because of a crisis, such as a natural or man-made disaster, it is critical that freight flow is not disrupted. We develop a simulation model that can be used to make effective re-routing decisions so that the time for freight to reach its final destination is not significantly increased in a crisis. The simulation model will evaluate and report the performance of the supply chain under different re-routing strategies. The output can be analyzed to find the best re-routing strategy that minimizes congestion and delays during crisis conditions. The model can also be used by various decision makers such as port managers, ocean carriers, or transportation companies for strategic decision making.
Detection of recombinant human erythropoietin in urine by isoelectric focusing.

Background: Doping with erythropoietic proteins such as recombinant human erythropoietin (rHuEPO) and darbepoetin alfa is a serious issue in sport. There is little information on the time course of detection of rHuEPO in urine and on methods to evaluate electrophoresis-based data. Methods: We used a recently described isoelectric focusing method for detecting rHuEPO and endogenous EPO in urine obtained from individuals treated with placebo or epoetin alfa. The latter was administered subcutaneously at 50 IU/kg on days 0, 2, 4, 7, 9, 11, 14, 16, and 18. Blood and urine samples were collected during the morning of study days −3, 0, 2, 4, 7, 9, 11, 14, 16, and 18 and on days 2, 3, 4, and 7 postadministration. We developed visual and numerical (two-band ratio) techniques to evaluate the electropherograms for the presence of rHuEPO. Results: Compared with the placebo group, the epoetin alfa-treated group responded with increases in hematocrit, reticulocytes, macrocytes, serum EPO, and serum soluble transferrin receptor. The electropherograms showed that the pattern of bands arising from urinary rHuEPO is different from that of endogenous urinary EPO. Both the two-band ratio and the visual technique detected rHuEPO in all 14 epoetin alfa-treated individuals 3 days after the last dose. On the 7th day after the last dose, both techniques detected rHuEPO in approximately one-half of the participants. rHuEPO was not detected in the placebo-treated individuals. Conclusions: The isoelectric focusing method detects rHuEPO in most urine samples collected 3 days after nine doses of epoetin alfa. The numerical two-band ratio was equivalent to a visual method for detecting rHuEPO in urine.
IS THE “NATURAL ORDER” AN ARTIFACT OF THE BILINGUAL SYNTAX MEASURE?

In a recent study, Porter (1977) reported that the rank order for grammatical morphemes in obligatory contexts between child first language acquirers using the BSM was “moderately dissimilar” to that found for child second language acquirers using the BSM. Also, correlations between the L1 BSM order and child L1 orders obtained from spontaneous speech are “highly dissimilar”. He suggests that the order obtained with the BSM could be “an artifact of the testing situation” and should be validated using spontaneous speech of second language performers. This paper makes three points about these conclusions. (1) Spontaneous speech data has been provided since Porter's paper was written, and there appears to be clear agreement between BSM and spontaneous speech (and writing) morpheme orders. (2) The BSM L1 order found by Porter is not “highly dissimilar” to child L1 order obtained using spontaneous speech, as the rank order correlation (rho =.67, n = 7) is quite close to statistical significance. (3) The degree of similarity between Porter's L1 order and BSM L2 orders is not inconsistent with previous findings. This suggests that the “natural order” found using the BSM for second language acquirers is not an artifact of the test.
REPLICATION OF THE FACTOR STRUCTURE OF THE COMREY PERSONALITY SCALES

The factor structure of the Comrey Personality Scales was replicated using a sample of suburban Denver residents (N = 377). Correlations are reported between the Comrey scales and age, socioeconomic status, sex, body type, a short locus of control scale, the Raven Progressive Matrices Test, and the Neuroticism and Extraversion scales from the Eysenck Personality Questionnaire. Correlations with self-reported leisure time activities and nervous habits provide a partial validation of the Comrey Activity, Stability, and Extraversion scales.
Ventilatory Pattern Variability in Mammals

The mammalian ventilatory control system consists of coordinated actions of the central and peripheral nervous systems and muscles of breathing to effect dynamic expansions and contractions of the lungs. Mechanical and chemical feedbacks report on the status of the process in order to keep blood gas tensions of oxygen and carbon dioxide within homeostatic ranges. As a result of the nonlinear interactions of numerous variables, differential phasic delays between efferent and afferent signals, and the presence of noise and environmental perturbations, variables of breathing (tidal volume, cycle durations, etc.) normally exhibit fluctuations over many different time scales. Loss of dynamic flexibility because of central nervous system (CNS) damage or cardiovascular compromise can lead to abnormal and ominous breathing patterns incompatible with life. Mathematical models of ventilatory control instruct on how the breathing system is regulated in health and disease. Keywords: respiratory patterns; nonlinear dynamics; nonstationary signals; models of breathing
Zinc‐dependent dimerization of the folding catalyst, protein disulfide isomerase

Protein disulfide isomerase (PDI), an essential folding catalyst and chaperone of the endoplasmic reticulum (ER), has four structural domains (a-b-b′-a′-) of approximately equal size. Each domain has sequence or structural homology with thioredoxin. Sedimentation equilibrium and velocity experiments show that PDI is an elongated monomer (axial ratio 5.7), suggesting that the four thioredoxin domains are extended. In the presence of physiological levels ( 600 kDa). Because of a very high concentration of PDI in the ER, its interaction with divalent ions could play a role in regulating the effective concentration of these metal ions, protecting against metal toxicity, or affecting the activity of other (ER) proteins that use Zn2+ as a cofactor.
The CAT-CAM socket and quadrilateral socket: A comparison of energy cost during ambulation

Twenty unilateral trans-femoral amputees fitted with either the Contoured Adducted Trochanteric-Controlled Alignment Method (CAT-CAM) socket (n=10) or the quadrilateral (QUAD) socket (n=10), and a ...
Experimental validation of FINDSITE comb virtual ligand screening results for eight proteins yields novel nanomolar and micromolar binders

Identification of ligand-protein binding interactions is a critical step in drug discovery. Experimental screening of large chemical libraries, in spite of their specific role and importance in drug discovery, suffer from the disadvantages of being random, time-consuming and expensive. To accelerate the process, traditional structure- or ligand-based VLS approaches are combined with experimental high-throughput screening, HTS. Often a single protein or, at most, a protein family is considered. Large scale VLS benchmarking across diverse protein families is rarely done, and the reported success rate is very low. Here, we demonstrate the experimental HTS validation of a novel VLS approach, FINDSITEcomb, across a diverse set of medically-relevant proteins. For eight different proteins belonging to different fold-classes and from diverse organisms, the top 1% of FINDSITEcomb’s VLS predictions were tested, and depending on the protein target, 4%-47% of the predicted ligands were shown to bind with μM or better affinities. In total, 47 small molecule binders were identified. Low nanomolar (nM) binders for dihydrofolate reductase and protein tyrosine phosphatases (PTPs) and micromolar binders for the other proteins were identified. Six novel molecules had cytotoxic activity (<10 μg/ml) against the HCT-116 colon carcinoma cell line and one novel molecule had potent antibacterial activity. We show that FINDSITEcomb is a promising new VLS approach that can assist drug discovery.
The whole heaven a musical scale and a number.

Suggested citation for this article: Potter P. The whole heaven a musical scale and a number. Emerg Infect Dis [serial on the Internet]. 2010 May [date cited]. http://www.cdc.gov/EID/content/16/5/905.htm
Neuroscience nursing interactive patient vignette.

A regular feature of this section will be the presentation of hypothetical cases. The purpose of these case presentations is to inspire discussion about some of the more difficult decisions in neuroscience nursing. Interspersed throughout each case will be set of questions about what the optimal management should be at that point. All of the readers will be invited to vote on those answers using a link to a survey https://www.surveymonkey.com/s/snicases. Please try to answer each question as you go through the case rather than finishing the case before answering the questions. The results of the survey will be presented in the subsequent issue. All readers are encouraged to send comments to the editor regarding the results of the survey and important discussion points arising highlighted in that or later issues. These cases can be used by any of the readers at their own institutions to spark discussions. Nothing in these case presentations is to be taken as a suggestion for patient management as the hypothetical cases may feature both medically appropriate and medically inappropriate decisions. The key is the discussion that follows.
Room-risk management at Sunquest vacations.

This article outlines some of the basic complexities that originate with the acquisition of hotel rooms for a reseller of bundled vacations. A tour operator typically acquires or contracts for serv...
Design, development and teaching of innovative Web-based introductory "Computer Information Systems" course

The state-of-the-art InterLabs Web-lecturing tool has been designed, developed, and tested at the Department of Computer Science and Information Systems and the InterLabs Research Institute, Bradley University, Peoria, Illinois as a part of a National Science Foundation grant. It is based on active utilization of innovative Web-based software engineering, portal, multiagent, streaming multimedia, communication, teaching, learning and information technologies. The introductory "Computer Information Systems" CIS102 course is a required course for all freshman students with major in either engineering, business, science or education areas. As a result, the innovative Web-based CIS102 course was aimed to (1) provide students of various major areas with highest-possible learning convenience, and (2) meet different requirements for CIS102 course of various Bradley departments. The new CIS102 online course was designed and developed by faculty of the Computer Science and Information Systems department in cooperation with faculty from other Bradley colleges. Student formative and summative evaluations and academic performance clearly demonstrate the advantages of the innovative online teaching and learning technologies based on the InterLabs Web-lecturing tool.
The Effects of Psychosocial Factors on Quality of Life Among Individuals With Chronic Pain

This study investigated the psychosocial factors affecting the quality of life (QOL) of 171 individuals with chronic pain. Participants completed a battery of self-rated inventories measuring three...
Prolongation of skin allograft survival is associated with reduced Th1 cytokine responses in the WKY-->F344 rat model.

BACKGROUND We have reported previously that F344 rats develop a spontaneous tolerance to WKY lung allografts and show long-term retention of donor-specific skin grafts placed 35 days after lung transplantation. In this study, we investigated the immunologic mechanisms that may be responsible for the prolonged skin graft survival in animals tolerized with lung allografts. METHODS In the rejection group, WKY skin grafts were placed on normal F344 rats, whereas, in the tolerance group, the skin grafts were placed on F344 rats that had received a WKY lung transplant 35 days before skin grafting. Th1 (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and Th2 (IL-4 and IL-10) cytokine as well as transforming growth factor-beta1 mRNA expression in skin grafts and in draining lymph nodes were determined by reverse transcription-polymerase chain reaction. Macrophage and lymphocyte infiltration in skin grafts and the number of Langerhans cells in epidermal sheets of the grafts were examined by immunohistochemistry. RESULTS IL-2 and IFN-gamma mRNA expression was significantly decreased in both the skin grafts and the draining lymph nodes of the tolerance group, compared to the rejection group, whereas IL-10 and transforming growth factor-beta1 mRNA expression was similar in both groups and IL-4 mRNA was rarely detected. Decreased and delayed CD8+, macrophage, and natural killer cell infiltration in the skin grafts from the tolerance group was also detected. Similar reduction in the number of Langerhans cells in the epidermis of the grafts from both groups was seen on day 1 after skin grafting, and thereafter the number remained stable in both groups. CONCLUSIONS Reduced expression of Th1 cytokines and decreased infiltration of CD8+ cells, macrophages, and natural killer cells in the skin grafts may be responsible for prolongation of skin graft survival in the tolerance group.
Marked increase in L-selectin-negative T cells in neonatal pertussis. The lymphocytosis explained?

The detailed immunophenotype of peripheral blood lymphocytes from a neonate with pertussis was determined by flow cytometry and compared with results from cord blood from healthy newborns. Most (72%) of the lymphocytes were CD3+ T cells with a normal CD4/CD8 ratio (2.5). The T cells were largely HLA-DR negative and CD45RA+, consistent with unstimulated naive T cells. Almost all of the CD4+ T cells were Leu8 (L-selectin, CD62L) negative, while almost all of the CD8+ T cells were CD28+. There was no increase in CD7- CD4+ T cells (Th2-like). No relative increase in CD16/56+ NK cells (5%) or CD19/20+ B cells was seen. The most dramatic finding in this case was the remarkable lack of expression of L-selectin by the T cells. L-selectin expression is associated with homing of peripheral blood lymphocytes to lymph nodes. The dramatic reduction in L-selectin expression of the T lymphocytes in pertussis, perhaps induced by pertussis toxin, likely prevents homing of the T cells to peripheral lymphoid tissues and provides a likely explanation for the marked lymphocytosis noted in this disease.
N,N′‐Bis(trimethylsilyl)urea

[18297-67-7] C7H20N2OSi2 (MW 204.42) InChI = 1S/C7H20N2OSi2/c1-11(2,3)8-7(10)9-12(4,5)6/h1-6H3,(H2,8,9,10) InChIKey = MASDFXZJIDNRTR-UHFFFAOYSA-N (large-scale silylating reagent for alcohols and carboxylic acids;1b does not require acid or base catalysis and the urea byproduct is insoluble in CH2Cl2, which aids in the reaction workup) Alternate Name: BSU. Physical Data: mp 232 °C (dec). Form Supplied in: white powder. Handling, Storage, and Precautions: when using, wear protective clothing to prevent contact with eyes and skin. May cause irritation if inhaled, ingested, or comes in contact with skin. Toxicological properties have not been thoroughly investigated. Store in a cool dry place, under an inert atmosphere to prevent hydrolysis.
Glucocorticoid suppression of urinary testosterone excretion in patients with idiopathic hirsutism.

Twelve patients with idiopathic hirsutism were studied. Seven had irregular or absent menses. None had male pattern baldness, clitoral hypertrophy, palpably enlarged ovaries or a major defect in cortisol production. Urinary excretion of 17-ketosteroids (17-KS) was increased in 7 patients and urinary excretion of testosterone glucuronide (testosterone-G) was increased in 11 patients. Small doses of glucocorticoids were administered orally to all patients for 2–16 months. Three randomly assigned schedules of glucocorticoid administration were used. Glucocorticoid therapy caused the urinary excretion of 17-KS and testosterone-G to fall to normal or less than normal in all patients regardless of which schedule of drug administration was used. In 8 patients either menses became normal, hirsutism diminished or both occurred. One month after cessation of therapy most patients continued to excrete normal amounts of urinary 17-KS and testosterone-G. These data suggest that in some patients with idiopathic hirsutis...
Animating to improve learning: a model for studying multimedia effectiveness

This paper presents a model for designing experiments to test the effectiveness of multimedia in education. It is based upon a discussion of an experimental study that examined the impact of one specific multimedia enhancement-animation-on a very specific aspect of learning-the ability to apply knowledge. The prospect of multimedia as a tool that can enrich a learning environment is quite alluring. The potential to actively engage learners through multiple communication channels is, intuitively, very compelling as a means of promoting learning for a larger percentage of students. This enthusiasm must, however, be tempered by two sobering facts. The cost of multimedia production is so very great that, should it not prove effective, our educational system could be seriously impacted. Perhaps more importantly, there is little scientific evidence in support of the value of multimedia as an enhancement to a learning environment. The paucity of substantial evidence supporting the value of multimedia as an educational enhancement can at least partially be attributed to definitional problems within experimental designs. What specifically does "learning", and, for that matter, "multimedia", mean? If these terms are not explicitly defined and intimately incorporated into the experimental controls, there is little hope for creditable results. This study indicates that careful attention to defining these two terms can produce meaningful results.
A cleavable affinity biotinylating agent reveals a retinoid binding role for RPE65.

Retinal pigment epithelial (RPE) membranes contain the full biochemical apparatus capable of processing all-trans-retinol (vitamin A) into 11-cis-retinal, the visual chromophore. As many of these proteins are integral membrane proteins and resistant to traditional methods of identification, alternate methods of identifying these proteins are sought. The approach described here involves affinity biotinylation with alkali cleavable linkers. A vitamin A containing affinity-labeling haloacetate is described which facilitates the identification of retinoid binding proteins (RBPs). Treatment of crude bovine RPE membranes with (3R)-3-(boc-lys(biotinyl)-O)-all-trans-retinol chloroacetate 1 in the low micromolar range led to the specific labeling of RPE65 and lecithin retinol acyltransferase (LRAT). Only RPE65 is labeled at 5 IM 1 at 4 °C. Labeled RPE65 was readily isolated by binding the labeled protein to avidin-containing beads, followed by cleavage of the protein from the beads at pH 11. Trypsin digestion of RPE65 modified by 1, followed by mass spectrometry, demonstrates that C231 and C448 are alkylated by 1. These studies validate the approach that was used, and furthermore demonstrate that RPE65, a major membrane-associated protein of the RPE, is a RBP.
Managing the risk of terrorism to interdependent infrastructure systems through the dynamic inoperability input–output model

This paper discusses the Dynamic Input–Output Inoperability Model (DIIM), which is an extension to the static Inoperability Input–Output Model (IIM). Based on Wassily Leontief's Input–Output (I–O) model, both the IIM and the DIIM analyze how the system of interdependent sectors can be adversely affected as a result of initial perturbations to other sectors through willful attacks or natural disasters. To model the industry/sector interdependencies, the DIIM uses the national and regional commodity-transaction data from the Bureau of Economic Analysis (BEA) and the Regional Input–Output Multiplier System (RIMS II). In contrast to most traditional dynamic I–O models, the DIIM introduces industry resilience coefficients to measure the efficacy of sectors' risk management options. The DIIM also incorporates the stochastic properties of a recovery through the Brownian motion, representing short-term uncertainties. The paper uses two metrics to assess the consequences to the economic sectors of attacks. The DIIM methodology is demonstrated in detail through a two-by-two economy system. This is followed by an analysis of a terrorist attack scenario, using the DIIM and the BEA/RIMS II commodity-flow data of the 59 sectors in Virginia. © 2006 Wiley Periodicals, Inc. Syst Eng 9: 241–258, 2006. DOI 10.1002/sys.20051(National Science Foundation, University of Virginia Center for Risk Management of Engineering Systems (NSF 0301553: Input-Output Risk Model of Critical Infrastructure Systems, Institute for Information Infrastructure Protection (I3P), Grant 2003-TK-TX-0003 from the Office of Domestic Preparedness of the U.S. Department of Homeland Security.)
Factors involved in a smooth transition to ISDNs

The authors deal with the major issues concerning a smooth transition to integrated services digital networks (ISDNs). It is noted that the goals of technology improvements, cost/performance, effectiveness, user acceptance of ISDN services, conversion of networks' operation to all digital, and standardization are essential for the economic acceptance by the ISDN user. The uses of ISDNs are not completely known at this stage. Therefore, it is not easy to accurately plan for ISDNs. The authors elaborate on these issues, their possible solutions, and their effects on the developments of ISDNs. >
Leader peptides of inducible chloramphenicol resistance genes from gram-positive and gram-negative bacteria bind to yeast and Archaea large subunit rRNA.

catA86 is the second gene in a constitutively transcribed, two-gene operon cloned from Bacillus pumilus . The region that intervenes between the upstream gene, termed the leader, and the catA86 coding sequence contains a pair of inverted repeat sequences which cause sequestration of the catA86 ribosome binding site in mRNA secondary structure. As a consequence, the catA86 coding sequence is untranslatable in the absence of inducer. Translation of the catA86 coding sequence is induced by chloramphenicol in Gram-positives and induction requires a function of the leader coding sequence. The leader-encoded peptide has been proposed to instruct its translating ribosome to pause at leader codon 6, enabling chloramphenicol to stall the ribosome at that site. Ribosome stalling causes destabilization of the RNA secondary structure, exposing the catA86 ribosome binding site, allowing activation of its translation. A comparable mechanism of induction by chloramphenicol has been proposed for the regulated cmlA gene from Gram-negative bacteria. The catA86 and cmlA leader-encoded peptides are in vitro inhibitors of peptidyl transferase, which is thought to be the basis for selection of the site of ribosome stalling. Both leader-encoded peptides have been shown to alter the secondary structure of Escherichia coli 23S rRNA in vitro. All peptide-induced changes in rRNA conformation are within domains IV and V, which contains the peptidyl transferase center. Here we demonstrate that the leader peptides alter the conformation of domains IV and V of large subunit rRNA from yeast and a representative of the Archaea. The rRNA target for binding the leader peptides is therefore conserved across kingdoms.