cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancers of hypermutation.

Hypermutation at the immunoglobulin (Ig) loci increases the mutation rate more than 105-fold over the normal, spontaneous rate. We studied two kinds of cis-acting elements – 3′ enhancers and promoters – in a system in which a gene encoding the μ heavy (H) chain (Igm) is transfected in vitro into a cell line with an active Ig mutator. A construct containing a rearranged Igm gene requires the 3′H enhancer for hypermutation at a rate comparable with the one at the endogenous gene segment encoding the H chain variable region (V). Without the 3′ enhancer, the basal mutational activity is much lower, but still higher than the normal, spontaneous mutation rate. Replacement of the 3′H enhancer by atopic elements of similar function also supports full hypermutation. Even though these 3′ elements are defined as transcriptional enhancers, they do not seem to increase hypermutation via an increase in the rate of transcription. Replacement of the endogenous promoter by the tk promoter slightly increases hypermutability of the construct; thus, no specific sequences in the Ig promoter are likely to target hypermutation.
Randomized trial of parent management training in children with tic disorders and disruptive behavior.

Oppositional, defiant, and disruptive behaviors are common in clinical samples of children with tic disorders. In this study, we sought to evaluate the short-term efficacy of a structured parent tr...
Piecewise linear models of processor utilization

Abstract This paper is part of a larger research effort to characterize the performance of parallel programs on distributed memory multiprocessors. We consider modeling processor utilization data by continuous piecewise linear approximations. We describe interactive tools for the identification of underlying trends and for the suppression of superfluous detail in processor utilization graphs.
Seasonal patterns of sea-surface temperature and ocean color around the Galápagos: regional and local influences ☆

Abstract Monthly climatologies of satellite-derived sea-surface temperature (SST, from AVHRR) and ocean color (from Ocean Color and Temperature Scanner and Sea-viewing Wide-Field-of-view Sensor) around the Galapagos Archipelago are used to estimate the mean seasonal cycle of these properties and their relationship to the equatorial circulation in this oceanographically complex region. Harmonic analysis of the climatological time series indicates a best fit with annual and semi-annual constituents. The annual amplitude is the dominant signal in SST, corresponding to the basin-wide seasonal cycle of warming and cooling associated with the north–south migration of the intertropical convergence zone. Influx of upwelled water from the Panama Bight into the northeastern part of the study area is also consistent with the annual signal. An empirical orthogonal function decomposition identifies two main spatial patterns with amplitude time series representing out-of-phase annual cycles. The dominant mode corresponds to the strengthening of the Equatorial Front and the South Equatorial Current during the second part of the year. This mode explains 92.2% of the SST variance and 82.9% of the ocean-color variance. The second mode is consistent with the topographically induced upwelling of the Equatorial Undercurrent on the western side of the archipelago, and with influx of upwelled Panama Bight water on the eastern side, both reaching their peak during the first part of the year. This mode accounts for 6% of the SST variance and 7.7% of the ocean-color variance. The seasonal evolution of water-column temperature and nitrate (from World Ocean Atlas 1998 climatologies) is consistent with the satellite-derived patterns. A slight tilt aligned with the east–west axis of the Galapagos Platform (outlined by the 2000-m isobath) is evident in all property fields, suggesting that the presence of the archipelago introduces a small but noticeable perturbation to the large-scale currents and property gradients of the eastern equatorial Pacific.
Effect of Ration on Freezing Point of Milk and Blood Serum of the Dairy Cow

Abstract This investigation consisted of two parts: 1) A stall-feeding experiment conducted during the winter, to determine the effect of a low-protein, high-saturated-fat ration on the freezing points of blood serum and milk in the dairy cow, and 2) a pasture experiment conducted during the summer, to determine the effect of restricted roughage intake on the freezing point of milk. Sudden or radical changes in the ration appeared to have an effect on the freezing point of milk, the Jerseys being affected to a greater extent than the Holsteins. Jersey milk also had a lower freezing point than the Holstein milk when the animals were fed normal rations, although the difference was not statistically significant. Changes in ration had less effect on freezing point of blood serum than on freezing point of milk. There was no significant correlation between freezing points of milk and blood serum. The experimental feeding regime had no significant effect on the total solids, milk fat, or solids-not-fat content of the milk.
NEUTRALIZATION OF ANTIMICROBIAL PROPERTIES OF LAURICIDIN BY TWEENS

The antimicrobial activities of Lauricidin (glycerol monolaurate) and its formulations Lauricidin Plus F, and Lauricidin 812 were neutralized by Tweens 20 and 80. The quantitative relationship depended on the formulation of Lauricidin, the test organism and the concentration of the Tweens. In general Tween 20 and Tween 80 were similar in their abilities to neutralize the antimicrobial properties of Lauricidin. In most cases, (74% of the observations) 3.0% Tweens completely neutralized Lauricidin and its formulations. The effects of the Tweens on Lauricidin and Lauricidin Plus F were also studied quantitatively. In the presence of Lauricidin and Tweens, no inhibition was noticed and in most cases, the viable count was similar to the control. Lauricidin Plus F was much more potent than Lauricidin in inhibiting the organisms tested and the restoration of growth in the presence of the Tweens was not complete. The viable counts in the presence of Lauricidin Plus F and the Tweens were about two or more log cycles lower than the control.
A Case of Late Kidney Allograft Failure: A Clinical Pathological Conference from American Society of Nephrology Kidney Week 2011

With the advent of more potent immunosuppression, early outcomes after kidney transplantation have been excellent. However, long-term graft survival has improved at a slower pace and does not reflect the substantial gains made in the early post-transplant period ([1][1]). Identification of the
Gender Bias in Leader Evaluations Merging Implicit Theories and Role Congruity Perspectives

This research extends our understanding of gender bias in leader evaluations by merging role congruity and implicit theory perspectives. We tested and found support for the prediction that the link between people's attitudes regarding women in authority and their subsequent gender-biased leader evaluations is significantly stronger for entity theorists (those who believe attributes are fixed) relative to incremental theorists (those who believe attributes are malleable). In Study 1, 147 participants evaluated male and female gubernatorial candidates. Results supported predictions, demonstrating that traditional attitudes toward women in authority significantly predicted a pro-male gender bias in leader evaluations (and progressive attitudes predicted a pro-female gender bias) with an especially strong effect for those with more entity-oriented, relative to incrementally oriented person theories. Study 2 (119 participants) replicated these findings and demonstrated the mediating role of these attitudes in linking gender stereotypes and leader role expectations to biased evaluations.
Evaluation of developmental toxicity of propylthiouracil and methimazole.

BACKGROUND Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs. METHODS We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20. RESULTS In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed. CONCLUSION We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy
Neuromyopharmacology as Related to Anticholinesterase Action

INTRODUCTION Skeletal neuromyal (NM) junction is one of the primary targets of either acute or chronic action of anticholinesterases (antiChE's) generally and of organophosphorus (OP) ChE inhibitors specifically (Karczmar, 1967a). In fact one of the first (Holmstedt, 1963; Karczmar, 1970) observations with respect to OP, acute or chronic administration, concerned the resulting muscle weakness. In the historical 1946 issue of the Journal of Pharmacology and Experimental Therapeutics where some of the results .obtained wi th OP agents at the US Army Chemical Center, Edgewood, MD, were published for the first time in open literatur~e, the neuromyal weakness was described as an overt symptom of systemic administration of OP antiChE's; also, it was emphasized that when it was attenuated wi th time in non-fatal cases upon discontinuation of the OP administration, the NM block reappeared, accompanied by fasciculations, upon stimulation of the.animal (Modell et aL, 1946; Modell and Krop, 1946; Koelle and Gilman, 1949). After the init iat ion of studies of isolated NM preparations this effect was related to non-substenance of tetanus or .to tetanic fade (Karczmar, 1967a; Hobbiger, 1976; Bowrn'an, 1979). As it wi l l be stressed here it appears today that still another factor may be involved in the antiChE induced muscle weakness, namely receptor desensitization. On the other hand, block of response to single indirect stimulation required very large in the neighborhood of 104M in the in vitro experiments concentrations of OP or non-OP antiChE's (Barstad and Lil leheil, 1968; Meer and Meeter, 1956; Fleisher et aL, 1960; Hobbiger, 1976). These as wel l as more recent data (Wills, 1970; Grob, 1963; Drachman, 1981 ) emphasize the significance of the NM junction in OP and, generally, antiChE poisoning. This presentation wi l l shift the focus of the NM action of antiChE's from its toxic to its basic aspects, as their synaptic effect on the NM transmission is of a particularly heuristic character. Some of the aspects of this action wi l l be reviewed as wi l l be the effect of antiChE's on desensitization and their interaction with drugs capable of antagonizing desensitization.
A smooth robust nonlinear controller for robot manipulators with joint stick-slip friction

The design of a smooth robust nonlinear controller for the regulation of an n-degree-of-freedom rigid robot with internal joint stick-slip friction is presented. It is shown that not only positioning accuracy, but also smoothness of motion is improved through nonlinear feedback. The Lyapunov direct method is employed to prove the global stability of the closed-loop system. The desired accuracy can be achieved by adjusting the parameters of the controller. The nonlinear compensator is robust with respect to the character of the slipping torque. Only the maximum static friction torque of the internal joint is required for controller design. The numerical implementation of this controller on a two-link robot is presented. >
The challenges and opportunities of designing pervasive systems for deep-space colonies

Space exploration is at an exciting yet challenging chapter in its history, with plans and preparations for the first human flight to Mars well underway. Our space flight capability has dramatically improved as a result of consistent technological advances coupled with a better understanding of the psychological and physiological effects of prolonged space flight on individuals and groups. Despite these advances, the usefulness and applicability of pervasive technologies (which is a mix of embedded, fixed and mobile networked interactive technologies) to space exploration is still limited, mostly restricted to tracking items onboard spaceships. While this situation is not likely to change in the near future, there still exists much potential for pervasive systems in the context of space exploration by humans. In this paper, we consider how, in the future, pervasive technologies can assist humans in deep-space colonies when space flight becomes commonplace. By considering today’s pervasive technologies in the context of deep space colonisation we make two contributions: (1) identify issues that future research should consider and (2) provide a shift in perspective which challenges the way we think about pervasive systems here on Earth. These two contributions are the challenges and opportunities of designing pervasive systems for deep-space colonies. In this paper, we draw on recent developments in largescale pervasive systems that consider whole cities as systems, and consider how such systems can be developed for and used in deep-space. We highlight these differences by discussing three topics:
PACE: an architectural style for trust management in decentralized applications

Distributed applications that lack a central, trustworthy authority for control and validation are properly termed decentralized. Multiple, independent agencies, or "partners", cooperate to achieve their separate goals. Issues of trust are paramount for designers of such partners. While the research literature has produced a variety of trust technology building blocks, few have attempted to articulate how these various technologies can regularly be composed to meet trust goals. This paper presents a particular, event-based, architectural style, PACE, that shows where and how to incorporate various types of trust-related technologies within a partner, positions the technologies with respect to the rest of the application, allows variation in the underlying network model, and works in a dynamic setting. Initial experiments with variants of two sample decentralized applications developed in the PACE style reveal the virtues of dealing with all aspects of application structure and trust in a comprehensive fashion.
An Evaluation of Path Planners for Guidance With Vision Based Simultaneous Localization and Mapping

This paper discusses implementation and compares results from three dierent path planning methods for guidance through a cluttered environment using vision-based simultaneous localization and mapping (SLAM). The planners are implemented using sequential quadratic programming (SQP), a genetic algorithm, and a rapidly-exploring random tree (RRT). Various planning horizon lengths are explored. The planners are compared for resulting path length from a start to a goal location and back, obstacle avoidance, and computation time. A short planning horizon SQP method resulted in shortest path lengths, a medium horizon genetic algorithm produced the best obstacle avoiding trajectories, and the short horizon SQP planner required the least planning time.
An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity.

Abstract An essential gene, designated HKE1/RAT1, has been isolated from the yeast Saccharomyces cerevisiae and characterized. The gene encodes a protein of 116 kDa (p116) and has significant homology to another yeast gene (XRN1/KEM1) encoding a related protein (p175) with 5'-->3' exonuclease activity as well as activities involving chromosomal DNA pairing and mechanics. Preliminary analysis of an hke1ts mutant reveals a precipitous decline in the translation of mRNA at the nonpermissive temperature. Sporulation of heterozygous HKE1/hke1::URA3 diploids reveals that this gene, unlike the highly related XRN1/KEM1 gene, is essential for cell viability. Overexpression of the homologous gene product, p175, failed to rescue cells lacking a functional p116. In vitro studies demonstrate that p116 is a protein with 5'-->3' exoribonuclease activity, a major activity of the related p175. An immunoreactive RNase activity of 116 kDa is abolished with antiserum against p116. Both the level of this protein and the RNase activity correlate with HKE1 gene dosage. The RNase activity purifies coincidentally with a previously described 116-kDa RNase having 5'-->3' exoribonuclease activity.
Dependence of the correlation of small scale photospheric structures upon resolution.

Correlations between continuum intensity, velocity, and equivalent widths of two Mn i lines as observed with two different entrance apertures tend to deteriorate with improvement in spatial resolution. The KPNO multichannel magnetograph was used to make area scans at the center of the disk with entrance apertures 3.5″×2.5″ arc and 1″×1″ arc. A coherence analysis shows that this effect is caused by marked differences of fluctuations in temperature and temperature gradients as well as in the velocity structure of photospheric elements of various sizes.
Electromagnetic fields from pulsed electron beam experiments in space - Spacelab-2 results

During the Spacelab-2 mission a small satellite carrying various plasma diagnostic instruments was released from the Shuttle to coorbit at distances up to 300 m. During a magnetic conjunction of the Shuttle and the satellite an electron beam modulated at 1.22 kHz was emitted from the Shuttle during a 7 min period. The spatial structure of the electromagnetic fields generated by the beam was observed from the satellite out to a distance of 153 m perpendicular to the beam. The magnetic field amplitude of the strongest harmonics were comparable to the amplitude of simultaneously observed whistlers, while the electric field amplitudes were estimated to 1-10 mV/m.
Couples therapy at end of life.

This study reports on a preliminary uncontrolled study of a treatment for couples in which one partner is diagnosed with a terminal illness. In this study nine couples, in which one partner was diagnosed with a terminal illness and had less than 18 months to live, were offered eight sessions of couples therapy. Follow-up data were available for six couples. Two patients died during treatment and a third patient moved out of the area prior to completing the follow-up assessment. Significant decreases were seen in the patients' distress about dying and the frequency of partners' worry about their partner dying. Improvements were also seen in relationship quality. While the size of the study precludes generalizing these findings to a larger population, this study supports further exploration of couples therapy as a potentially useful adjunct to end of life care. Copyright © 2003 John Wiley & Sons, Ltd.
Income Inequality and Health: A Critical Review of the Literature:

This article critically reviews published literature on the relationship between income inequality and health outcomes. Studies are systematically assessed in terms of design, data quality, measures, health outcomes, and covariates analyzed. At least 33 studies indicate a significant association between income inequality and health outcomes, while at least 12 studies do not find such an association. Inconsistencies include the following: (1) the model of health determinants is different in nearly every study, (2) income inequality measures and data are inconsistent, (3) studies are performed on different combinations of countries and/or states, (4) the time period in which studies are conducted is not consistent, and (5) health outcome measures differ. The relationship between income inequality and health is unclear. Future studies will require a more comprehensive model of health production that includes health system covariates, sufficient sample size, and adjustment for inconsistencies in income inequality data.
Crop Juxtaposition Affects Cotton Fiber Quality in Georgia Farmscapes

ABSTRACT Phytophagous stink bugs (Hemiptera: Pentatomidae), including green stink bug [Acrosternum hilare (Say)], southern green stink bug [Nezara viridula (L.)], and brown stink bug [Euschistus servus (Say)], have become a serious production issue for southeastern U.S. cotton, Gossypium hirsutum L., growers. To investigate how different agronomic crops may affect stink bug damage and fiber quality in neighboring cotton fields, replicated 1.6–2.0-ha trials were planted with corn (Zea mays L.), peanut (Arachis hypogaea L.), and soybean [Glycine max (L.) Merr.] bordering a centrally located cotton plot (each of the four crops composed of ≈0.4–0.5 ha per trial). Three trials were conducted in 2007 and three additional trials were conducted in 2008. Stink bug damage in the cotton plot was sampled weekly during weeks 3 through 6 of bloom at distances of 0.5, 5.3, 9.6, and 18.7 m from the adjacent crop. At the end of the year, representative lint samples at distances of 0.5, 9.6, 18.7, and 31.8 m from each adja...
Efficient in vitro RNA interference and immunofluorescence-based phenotype analysis in a human parasitic nematode, Brugia malayi.

Background: RNA interference (RNAi) is an efficient reverse genetics technique for investigating gene function in eukaryotes. The method has been widely used in model organisms, such as the free-living nematode Caenorhabditis elegans, where it has been deployed in genome-wide high throughput screens to identify genes involved in many cellular and developmental processes. However, RNAi techniques have not translated efficiently to animal parasitic nematodes that afflict humans, livestock and companion animals across the globe, creating a dependency on data tentatively inferred from C. elegans. Results: We report improved and effective in vitro RNAi procedures we have developed using heterogeneous short interfering RNA (hsiRNA) mixtures that when coupled with optimized immunostaining techniques yield detailed analysis of cytological defects in the human parasitic nematode, Brugia malayi. The cellular disorganization observed in B. malayi embryos following RNAi targeting the genes encoding g-tubulin, and the polarity determinant protein, PAR-1, faithfully phenocopy the known defects associated with gene silencing of their C. elegans orthologs. Targeting the B. malayi cell junction protein, AJM-1 gave a similar but more severe phenotype than that observed in C. elegans. Cellular phenotypes induced by our in vitro RNAi procedure can be observed by immunofluorescence in as little as one week. Conclusions: We observed cytological defects following RNAi targeting all seven B. malayi transcripts tested and the phenotypes mirror those documented for orthologous genes in the model organism C. elegans. This highlights the reliability, effectiveness and specificity of our RNAi and immunostaining procedures. We anticipate that these techniques will be widely applicable to other important animal parasitic nematodes, which have hitherto been mostly refractory to such genetic analysis.
Statistical artifacts in diffusion tensor MRI (DT-MRI) caused by background noise.

This work helps elucidate how background noise introduces statistical artifacts in the distribution of the sorted eigenvalues and eigenvectors in diffusion tensor MRI (DT-MRI) data. Although it was known that sorting eigenvalues (principal diffusivities) by magnitude introduces a bias in their sample mean within a homogeneous region of interest (ROI), here it is shown that magnitude sorting also introduces a significant bias in the variance of the sample mean eigenvalues. New methods are presented to calculate the mean and variance of the eigenvectors of the diffusion tensor, based on a dyadic tensor representation of eigenvalue‐ eigenvector pairs. Based on their use it is shown that sorting eigenvalues by magnitude also introduces a bias in the mean and the variance of the sample eigenvectors (principal directions). This required the development of new methods to calculate the mean and variance of the eigenvectors of the diffusion tensor, based on a dyadic tensor representation of eigenvalue‐ eigenvector pairs. Moreover, a new approach is proposed to order these pairs within an ROI. To do this, a correspondence between each principal axis of the diffusion ellipsoid, an eigenvalue‐ eigenvector pair, and a dyadic tensor constructed from it is exploited. A measure of overlap between principal axes of diffusion ellipsoids in different voxels is defined that employs projections between these dyadic tensors. The optimal eigenvalue assignment within an ROI maximizes this overlap. Bias in the estimate of the mean and of the variance of the eigenvalues and of their corresponding eigenvectors is reduced in DT-MRI experiments and in Monte Carlo simulations of such experiments. Improvement is most significant in isotropic regions, but some is also observed in anisotropic regions. This statistical framework should enhance our ability to characterize microstructure and architecture of healthy tissue, and help to assess its changes in development, disease, and degeneration. Mitigating these artifacts should also improve the characterization of diffusion anisotropy and the elucidation of fiber-tract trajectories in the brain and in other fibrous tissues. Magn Reson Med 44:41‐50, 2000. Published 2000 Wiley-Liss, Inc.†
Anti-gene padlocks eliminate Escherichia coli based on their genotype

Methods: The strategy employs an oligonucleotide with a double hairpin structure where both strands of the AGP are complementary to both strands of a target gene. We tested AGPs for in vitro binding and inhibition of DNA polymerization. AGPs were electroporated into bacterial cells with and without gene targets along with an ampicillin resistance plasmid, and cell survival was measured. Results: In vitro, AGPs bound the DNA target in a sequence-dependent fashion and inhibited DNA synthesis. When transformed into bacterial cells containing 10, 20 or 30 bp lacZ or 20 bp proA DNA targets in their genomes, AGPs selectively killed or otherwise inhibited growth of these cells, while those lacking the target demonstrated little, if any, toxicity. A single transformation resulted in 30% to 40% loss of target-bearing cells. Structure–function experiments were performed to define essential AGP requirements. Conclusions: These results suggest that AGPs may be a useful tool to eliminate specific cell populations.
Orthogonal Components of the Kruskal-Wallis and Related K-sample Linear Rank Statistics

It is shown that the KRUSKAL-WALLIS statistic may be decomposed into components designed to detect trends in the underlying distributions. Extensions to other K sample linear rank statistics and to nonparametric regression statistics are noted.
Diversity and specificity of Caribbean sponge-zoanthid symbioses: a foundation for understanding the adaptive significance of symbioses and generating hypotheses about higher-order systematics

The diversity and specificity of symbiotic associations may be useful in revealing the underlying ecology of symbioses and evolutionary relationships of symbiotic species. Symbioses between coral reef sponges and zoanthids are widespread and common in the greater Caribbean region, although the diversity and specificity of the species involved have only been explored at a few sites and the adaptive significance has only been examined for three combinations. We identified extensive diversity among sponges that associate with zoanthids by compiling sponge‐zoanthid species associations from field surveys, the literature, and museum collections, and examined the patterns of specificity at multiple levels of sponge and zoanthid taxonomy. The results obtained indicate that facultative sponges are highly specific to the species of their partners whereas obligate zoanthids are not. The patterns of specificity among sponges and zoanthids suggest that many of these associations are not likely to be parasitic. Sponges harbouring photosynthetic endosymbionts associate at a disproportionately high frequency with zoanthids that harbour photosynthetic endosymbionts. Zoanthids embed in the surfaces of sponges to various degrees, resulting in a range of intimacy that negatively correlates with the number of hosts and polyp volume of zoanthids. Dendrograms based on the similarity among associations are largely consistent with current hypotheses of sponge higher-order systematics, but inconsistent with the current hypotheses of zoanthid systematics, and they highlight the potential utility of ecological characters in systematic analyses. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society, 2007, 92, 695‐711. ADDITIONAL KEYWORDS: coral reefs ‐ Demospongia ‐ epibiont ‐ Macrocnemina ‐ mutualism ‐ parasitism ‐ photosynthetic endosymbionts ‐ similarity analysis ‐ symbiont intimacy ‐ symbiont size.
CD of six different conformational rearrangements of poly[(d(A-G)·d(C-T)] induced by low pH

Abstract On the basis of circular dichroism (CD) data, we have now identified six different conformational states (other than the duplex) of poly[d(A-G).d(C-T)] at pH values between 8 and 2.5 (at 0.01M Na+; 20 degrees C). Three of these structural rearrangements were observed as the pH was lowered from 8 to 2.5, and three additional rearrangements were observed as the pH was raised from 2.5 back to neutral pH. The major components of the six conformational states were defined using appropriate combinations of the CD spectra of the duplex, triplex, and denatured forms of this polymer, as well as the CD spectra of the individual single strands and their respective acid-induced self-complexes. Our results show that the acid-induced rearrangements of poly[d(A-G).d(C-T)] include not only the poly[d(C+-T).d(A-G).d(C-T)] triplex, but also include the poly[d(C-T)] loop-out structure and a self-complexed form of the poly[d(A-G)] strand that is pH-dependent.
Reply to Brynedal et al.: Accumulating genetic and functional evidence for a role of CD58 in multiple sclerosis

I am pleased that our recent article (1) has led to further exploration of the role of the CD58 locus in multiple sclerosis (MS) by Brynedal et al. (2).
Combined Néel and Brown rotational Langevin dynamics in magnetic particle imaging, sensing, and therapy

Magnetic nanoparticles have been studied intensely because of their possible uses in biomedical applications. Biosensing using the rotational freedom of particles has been used to detect biomarkers for cancer, hyperthermia therapy has been used to treat tumors, and magnetic particle imaging is a promising new imaging modality that can spatially resolve the concentration of nanoparticles. There are two mechanisms by which the magnetization of a nanoparticle can rotate, a fact that poses a challenge for applications that rely on precisely one mechanism. The challenge is exacerbated by the high sensitivity of the dominant mechanism to applied fields. Here, we demonstrate stochastic Langevin equation simulations for the combined rotation in magnetic nanoparticles exposed to oscillating applied fields typical to these applications to both highlight the existing relevant theory and quantify which mechanism should occur in various parameter ranges.
Sandwich immunoassay for the measurement of murine syndecan-4.

A sensitive and specific immunoassay for mouse syndecan-4 is described. The assay is a non-competitive direct sandwich enzyme-linked immunosorbent assay based on the production of an affinity-purified polyclonal antibody directed against syndecan-4 extracellular domain, used both as a trapping and detecting antibody. The standard curve is constructed with recombinant 6-His-tagged syndecan-4 extracellular domain. The assay allowed quantification of syndecan-4 core protein in the partially purified proteoglycan fraction from adipocyte 3T3-F442A cells, as well as in the cellular whole and clarified lysates. Removal of glycosaminoglycan chains on syndecan-4 core protein is required for maximal epitope exposure. The standard curve ranged between 7 and 70 fmol per well. For the 14 standard curves run on different days, the absorbance at 490 nm for 35.5 fmol of recombinant syndecan-4 was 0.610 ± 0.110 (n = 14) with a corresponding blank absorbance of 0.089 ± 0.030. At low (5.7 fmol) and high (42.8 fmol) levels of whole cell syndecan-4, the intra-assay and inter-assay coefficients of variation were 4.9 and 15.3 percent, and 3.3 and 9.7 percent, respectively. A survey of the syndecan-4 expression in various mouse tissues shows that syndecan-4 is highly expressed in the kidney, brain, testes and liver, but can also be measured in several different adipose tissue sites. —Rioux, R., R. Y. Landry, and A. Bensadoun. Sandwich immunoassay for the measurement of murine syndecan-4. J. Lipid Res. 2002. 43: 167–173.
Valuing the Spoken Word: Public Speaking for Lawyers

Public speaking - speaking to groups outside the litigation context - is an important part of many lawyers' practice, yet involves skills largely neglected in legal education. This neglect is consistent with the larger trends in public expression, particularly the triumph of formal over conversational language in public discourse and written texts over speech in intellectual discourse. This essay laments the current state of public speaking in legal culture and suggests a remedy by including a course in public speaking as a standard part of the law school curriculum.
Progress in the Discovery of Compounds Inhibiting Orthopoxviruses in Animal Models

Surrogate animal models must be used for testing antiviral agents against variola (smallpox) virus infections. Once developed, these, compounds can be stockpiled for use in the event of a bioterrorist incident involving either variola or monkeypox virus, or used to treat an occasional serious orthopoxvirus infection, such as disseminated vaccinia complication following exposure to the live virus vaccine. Recently, considerable progress has been made in the discovery of novel antiviral agents found active against orthopoxviruses in vivo. This includes the development of new animal models or refinement of existing ones for compound efficacy testing. Current mouse models employ ectromelia, cowpox and vaccinia (WR and IHD strains) viruses with respiratory (lung) or tail lesion infections commonly studied. Rabbitpox and vaccinia (WR strain) viruses are available for rabbit infections. Monkeypox and variola viruses are used for infecting monkeys. This review describes these and other animal models, and covers compounds found active in vivo from 2003 to date. Cidofovir, known to be active against orthopox virus infections prior to 2003, has been studied extensively over recent years. New compounds showing promise are orally active inhibitors of orthopoxvirus infections that include ether lipid prodrugs of cidofovir and (S)-HPMPA, ST-246, N-methanocarbathymidine (N-MCT) and SRI 21950 (a 4'-thio derivative of iododeoxyuridine). Another compound with high activity but requiring parenteral administration is HPMPO-DAPy. Further development of these compounds is warranted.
The first year: A cultural shift towards improving student progress

Student attrition has been a primary focus among higher education institutions for nearly 50 years, yet overall retention and graduation rates continue to be of significant concern. Despite increased attention, ongoing struggles of colleges and universities to effectively address potential barriers to student progress are well-documented. Part of the challenge lies in garnering widespread organizational commitment that establishes student progress as an institutional priority. Along with leadership commitment, broad institutional involvement and adherence to a systematic approach to testing new, innovative solutions are necessary to better position the institution to make clear, evidence-based decisions that improve the student experience. The purpose of this manuscript is to detail one university’s cultural shift towards establishing a clear student progress strategy (with particular focus on the first year), and the methodological approach that laid the foundation for a multi-year study of initiatives that resulted in improved student satisfaction, performance, and retention.
A Large-Eddy-Simulation Study of Combustion Dynamics of Bluff-Body Stabilized Flames

ABSTRACTA comprehensive numerical study is conducted to explore the dynamic behaviors of a flame stabilized by a triangular bluff body in a straight chamber. The formulation accommodates the complete set of conservation equations with turbulence closure achieved by a large eddy simulation (LES) technique. A G-equation-based level-set flamelet approach is employed to model the interactions between premixed combustion and turbulence. Both non-reacting and reacting flows are treated, with special attention given to the effect of inlet boundary conditions on the flame evolution. The flow around the bluff body consists of boundary layers, separated shear layers, a recirculation zone and a wake. Their mutual coupling, as well as interactions with acoustic motion and flame oscillation are analyzed in detail. The physical processes responsible for driving combustion instabilities and the mechanism of energy transfer from chemical reactions in the flame zone to acoustic oscillations in the bulk of the chamber are ...
Rod and Gun Activities

(1960). Rod and Gun Activities. Journal of Health, Physical Education, Recreation: Vol. 31, No. 5, pp. 70-70.
The Other Side of the Story: Knowledge Transfer and Advice-Giving in a Drug Subculture

ABSTRACTWidely used as a framework for understanding drug use initiation, social learning theory has lacked considerations of peer effects from the standpoint of the experienced user and applications to hard drugs. This study aims to extend social learning theory by examining the advice an experienced drug user would give a younger friend or relative expressing desire to experiment with club drugs. Forty qualitative interviews with club drugs users were analyzed. The experienced user’s own initiation, previous experiences, and risk perceptions are important in how advice is constructed. We discovered variations in advice-giving for friends and family members that may be based on considerations of age appropriateness.
Papilledima in Children

The use of oral fluorescein in the diagnosis of early papilledema in 23 children aged 1 mo to 10 yrs is reported from the Dr Rajendra Prasad Centre for Ophthalmic Sciences, All-India Inst of Med Sciences, Ansari Nagar, New Delhi, India.
Adsorption-enhanced hydrolysis of glucan oligomers into glucose over sulfonated three-dimensionally ordered mesoporous carbon catalysts

The hydrolysis of cellulose and β(1 → 4) oligosaccharides on carbon catalysts is a promising approach for the selective production of glucose from cellulose and its derivatives. In this study, a structure–property relationship was developed for the hydrolysis of water soluble glucan oligomers over three dimensionally ordered mesoporous (3DOm) carbon with sulfonic acid groups. It was found that the number of sulfonic acid groups on 3DOm carbon catalysts and their adsorption properties need to be optimized to maximize the hydrolysis of water soluble glucan oligomers. The adsorption capacity of glucan oligomers on 3DOm carbon increases with their chain length, which can be attributed to two molecular behaviors: (a) long glucan oligomers adsorbed on the carbon surface exhibit a dense packing structure compared with relatively small glucan oligomers; and (b) a part of a glucan oligomer “dangles” off the carbon surface due to its branched structure. It was found that the adsorption enthalpy and entropy increased with increasing the chain length of the glucan oligomers, which favors the hydrolysis reaction to produce glucose over the carbon catalysts.
Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

Background The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. Objective The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. Methods We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Results Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes ( P P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Conclusion Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart.
Effects of Stream Regulation on Channel Morphology

“The erosion cycle — detachment, transport, deposition — is described by the Second Law of Thermodynamics, which states each system tends to move in the direction of lowest energy. Because of the potential energy of soil (rock) in elevated positions and because of the kinetic energy of flowing water, all soil and water will move, eventually, to the lowest possible level, i.e., the ocean deeps, or to some temporary, intervening basin” (McHenry, 1964, 1969, 1974). The intervening basins, destined to be filled with sediment, include the reservoirs that we have become so dependent upon. We daily enjoy the benefits they provide, not fully realizing that they are continually filling and that, in the not so distant future, many will become useless. It is possible to accelerate or decelerate this process, but the filling is inevitable, given current knowledge. The reservoir’s life is dependent on sediment deposition. The under-standing of, and the ability to predict, both channel and reservoir response processes are extremely important. The rate and magnitude of changes experienced by watersheds and rivers depend on many naturally imposed factors, including floods, changes in the duration of specific flows, droughts, and changes in the water and sediment supply imposed by earthquakes, vertical changes in the earth’s crust, floods, and mass wasting.
Sporadic breast cancer in Chilean population: First array comparative genomic hybridization analysis

1736 In Chile, breast cancer is the second cause of death due to cancer among women and around 90% of all breast cancer cases are sporadic. The etiology and progression of breast cancer are associated with a series of genomic alterations, including genomic deletions and gene amplifications. For this reason we performed array-CGH in sporadic breast cancer biopsies (invasive ductal and in situ carcinoma) to search for regions with gains and losses in genomic DNA. In order to identify these genomic alterations Comparative Genomic Hybridization in microarray analysis was performed in platforms of 46.000 oligonucleotides. Genomic DNA was obtained from microdissected biopsies, and submitted to the analysis. In these biopsies we found as the most frequent genomic losses: 1q24_q25, 7q21.3 11p15, 11q22.3, 16q. The most frequent regions showing amplifications include: 1p13.3, 1q21, 1q43-q44, 8q, 17q. Some of these regions comprise genes previously involved in cancer as VAV 3 oncogene (vav 3 guanine nucleotide exchange factor), IL6R, AKT3 v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma), RNASEL, ST5 (suppression of tumorigenicity 5), ATM, NPAT. This is the first study of sporadic breast cancer in Chilean population using array-CGH. Since cancer is a genetic pathology influenced by environmental conditions, it is very relevant to characterize the pattern of genomic alterations in populations from different ethnic origins in order to compare the profiles and define if it is possible, common molecular markers of prognostic and therapy. Supported by FONDECYT Grants 3070021 and 1040779.
Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines.
Increased Frequency of KRAS Mutations in African Americans Compared with Caucasians in Sporadic Colorectal Cancer.

Increased Frequency of KRAS Mutations in African Americans Compared with Caucasians in Sporadic Colorectal Cancer
The TEMP Microcomputer as an Instrument Controller and Data Logger

The microprocessor is becoming an indispensible laboratory tool. To adapt it to one’s needs requires some basic understanding of its operation. With this understanding and some inexpensive integrated circuits, one can create custom interfaces for one’s own unique requirements.
Ephemeral Histories. Public Art, Politics, and the Struggle for the Streets in Chile, de Camilo Trumper

Ephemeral Histories. Public Art, Politics, and the Struggle for the Streets in Chile, de Camilo Trumper