cssi/SciSciGPT-SciSciNet huggingface dataset:
TH-D-BRB-02: Improving the Accuracy of Monte Carlo Spread-Out Bragg Peak Treatment Head Models Using Beam Current Modulation Optimization

Purpose: For challenging clinical cases Monte Carlo methods can help to verify the accuracy of proton beam planning results based on the pencil beam algorithm. However the use of Monte Carlo methods as a verification tool requires an accurate model of the proton fields generated in the treatment head. This paper presents a novel approach to improve upon the achievable accuracy of Monte Carlo models of proton beam treatment heads. We will also demonstrate the usefulness of this approach by presenting commissioning results of two treatment head models at our facility. Methods and Materials: The achievable accuracy of our treatment head model was examined by quantifying the impact of uncertainties in material and beam parameters on SOPB dose distributions. A novel approach to improve this accuracy was developed by optimizing the beam current modulation function defined in our Monte Carlo model to produce clinically acceptable SOBP dose distributions. Finally this method was utilized for the commissioning two models of SOBP proton beam treatment heads at our facility. Results: Uncertainty in material density led to the largest impact on the SOBP dose distributions (less than 4%). The impact of mean ionization potential uncertainties was smaller (less than 2%). We did not detect a statistically significant influence of clinically relevant beam energy spreads and spot sizes on the SOBP dose distribution. The optimization of our beam current modulation functions allowed us to fully commission two treatment head models at our facility. Conclusion: Several proton beam therapy centers are now operational or being planned and constructed which promises the future need for Monte Carlo modeling of proton beam therapy treatment heads. The methodology and results presented in this paper will help accommodate the commissioning of new Monte Carlo simulated treatment heads.
Sore throat after sore throat after sore throat: Are you asking the critical questions?

In this discussion of recurrent group A streptococcal tonsillopharyngitis, the author notes that even at the peak of the streptococcal infection season, not more than 30% to 40% of children with sore throats actually have group A streptococci as the cause. Thus, it is vital to confirm clinical diagnosis of group A streptococcal tonsillopharyngitis with laboratory tests. When patients have recurrent infections with group A streptococci, possible causes include noncompliance, bacterial resistance, repeated exposure, alteration of the throat's microbial ecology, suppression of antibody response due to previous antibiotic therapy, and treatment failure. When noncompliance is an issue, an injection of penicillin G benzathine may be appropriate. In other circumstances, pharmacologic options for treatment of recurrent group A streptococcal tonsillopharyngitis include macrolides, clindamycin hydrochloride, rifampin (in combination with a second agent), and oral cephalosporins. If a patient has six or seven recurrences over 1 or 2 years despite antibiotic treatment, tonsillectomy should be considered.
Fully Resolved Numerical Simulations of Fused Deposition Modeling

Fully resolved numerical simulations of the deposition of a filament of hot, viscous liquid, and its solidification, are presented. The computations are done using a front tracking/finite volume code designed for direct numerical simulations of multiphase flows, but here we add a volume source that follows a prescribed trajectory to inject the melt. The cooling of the melt is simulated and once it is cool enough the melt is solidified. The result suggest that the deposition is fully captured and that remelting of already solidified material results in a compaction of the deposited filaments.Copyright © 2014 by ASME
The Early Growth Response Gene Egr2 (Alias Krox20) Is a Novel Transcriptional Target of Transforming Growth Factor-β that Is Up-Regulated in Systemic Sclerosis and Mediates Profibrotic Responses

Although the early growth response-2 (Egr-2, alias Krox20) protein shows structural and functional similarities to Egr-1, these two related early-immediate transcription factors are nonredundant. Egr-2 plays essential roles in peripheral nerve myelination, adipogenesis, and immune tolerance; however, its regulation and role in tissue repair and fibrosis remain poorly understood. We show herein that transforming growth factor (TGF)-β induced a Smad3-dependent sustained stimulation of Egr2 gene expression in normal fibroblasts. Overexpression of Egr-2 was sufficient to stimulate collagen gene expression and myofibroblast differentiation, whereas these profibrotic TGF-β responses were attenuated in Egr-2–depleted fibroblasts. Genomewide transcriptional profiling revealed that multiple genes associated with tissue remodeling and wound healing were up-regulated by Egr-2, but the Egr-2–regulated gene expression profile overlapped only partially with the Egr-1–regulated gene profile. Levels of Egr-2 were elevated in lesional tissue from mice with bleomycin-induced scleroderma. Moreover, elevated Egr-2 was noted in biopsy specimens of skin and lung from patients with systemic sclerosis. These results provide the first evidence that Egr-2 is a functionally distinct transcription factor that is both necessary and sufficient for TGF-β–induced profibrotic responses and is aberrantly expressed in lesional tissue in systemic sclerosis and in a murine model of scleroderma. Together, these findings suggest that Egr-2 plays an important nonredundant role in the pathogenesis of fibrosis. Targeting Egr-2 might represent a novel therapeutic strategy to control fibrosis.
"Divided We Stand, United We Fall: Internal Coupling Structure and Business Group Failure"

The role of internal coupling structure in business groups is a central concern in the business group literature; yet, most empirical studies focus on the performance of affiliated firms. This study investigates how the extent of coupling among firms in a group affects group-level performance. Coupling creates interdependence among group firms and compounds risk within groups. Moreover, coupling buffers group firms from environmental selection so that coupled groups sustain weak firms that would have failed otherwise, consequently reducing the survival chances of the whole group. Based on this logic, I propose that the greater the coupling of group firms, the higher the group failure rate, especially in resource-scarce environments. A longitudinal analysis of 5,850 Korean business groups over a 20-year period, 1988-2007, supports my predictions. Tight coupling among affiliated firms in a group through corporate governance and internal transactions increases the failure rate of business groups, especially ...
The planar to cellular transition during the directional solidification of alloys

The planar to cellular interface transition during the directional solidification of a binary alloy has been studied in the succinonitrile-acetone system. The interface velocity at which the planar interface becomes unstable and the wave numbers of the initially unstable interface have been precisely determined and compared with the linear stability analysis. Critical experiments have been carried out to show that the planar to cellular bifurcation is subcritical so that a finite amplitude perturbation below the critical velocity can also give rise to planar interface instability.
A polymorphic PstI site in intron 2 of the human apolipoprotein C-II gene detected by polymerase chain reaction.

A previously unrecorded polymorphism of the human apolipoprotein C-II gene, with results in the loss of a PstI site is described.
THE USE OF FORMALDEHYDE-TREATED 131I-ALBUMIN IN THE STUDY OF DIGESTIVE VACUOLES AND SOME PROPERTIES OF THESE PARTICLES FROM MOUSE LIVER

The trichloroacetic acid-soluble radioactivity released during incubation of mouse liver particles containing intravenously injected formaldehyde-treated 131I-albumin consisted almost entirely of 131I-iodotyrosine. The material was shown to be excreted into the medium and was not due to disruption of the particles by acid. Triton X-100 or the absence of sucrose in the medium inhibited hydrolysis of the particle-associated labeled protein. This inhibition was due to disruption of the digestive vacuoles and dilution of the protein and cathepsins in the suspending medium. These results and other experimental evidence strongly suggest that the 131I-albumin-containing liver particles are digestive vacuoles. The results also establish that 131I-albumin may be used to study these vacuoles. High concentrations of sucrose (1 M) inhibited degradation of intraparticulate protein. However, 1 M salts inhibited only the rate of the digestion. Sucrose had an inhibitory effect on a crude cathepsin preparation, and salts stimulated the activity when 131I-albumin was used as substrate. The effect of high sucrose concentrations as an inhibitor of protein hydrolysis within digestive vacuoles was, therefore, most likely due principally to an inhibition of cathepsin activity within the vacuoles. The effect of salt was probably caused by a stimulation of both intra- and extra-particulate cathepsin activities, although 0.5–1.0 M KCl appeared to protect the particles.
Direct heat and mass transfer in structured packings

Abstract Direct heat transfer is an important method in the exchange of heat between two countercurrent process streams within a column. The process can be simulated using either the theoretical stage or the rate based concept. With both concepts, a reliable heat transfer coefficient is needed. Additionally, the rate of the heat transfer coefficient is influenced by the simultaneous mass transfer. A number of application-dependent methods to estimate the heat transfer coefficient have been developed, mainly for random packings. It is the purpose of this paper to extend this work to structured packings. A number of experiments with air/water have been performed in a column of 300 mm inner diameter with Mellapak 250.Y, 250.X and 125.X at ambient conditions. A second group of measurements were done using an oil/air system where only sensible heat was transferred. Based on these experimental results a method was developed to predict the heat transfer coefficient for structured packings. The method is applied to examples of industrial importance, like a gas quench, a gas saturator and a pump-around zone in an atmospheric tower.
UNRAVELING RELIGIOUS WORLDVIEWS : The Relationship between Images of God and Political Ideology in a Cross-Cultural Analysis

Not only do few studies address the issue of how religious belief relates to political ideology, but little attempt has also been made to analyze this relationship from a comparative perspective. Using data from the International Social Survey Program, we examine how images of God, as measured by God's perceived level of engagement and authority, relate to political ideology in seven Western industrial and postindustrial societies. We find that variation in images of God has no effect on whether individuals are politically liberal or conservative in five of seven countries. Nonetheless, beliefs about God are strongly related to abortion and sexual morality attitudes in every country, but only sporadically related to ideas about social and economic justice. In the end, we argue that theological beliefs tend to be unrelated to a general measure of political ideology, not because religious beliefs are politically unimportant in these societies, but rather because religious perspectives are rarely fully liberal or conservative in their political orientation. In addition, we find that Americans hold unique views of God in comparison to other countries in our sample and that the American tendency to view God as more active and authoritative affects policy attitudes in ways contrary to the effects of church attendance.
Synthesis and antiviral activity of 5-substituted cytidine analogues: identification of a potent inhibitor of viral RNA-dependent RNA polymerases.

As part of our studies of lethal viral mutagens, a series of 5-substituted cytidine analogues were synthesized and evaluated for antiviral activity. Among the compounds examined, 5-nitrocytidine was effective against poliovirus (PV) and coxsackievirus B3 (CVB3) and exhibited greater activity than the clinically employed drug ribavirin. Instead of promoting viral mutagenesis, 5-nitrocytidine triphosphate inhibited PV RNA-dependent RNA polymerase (Kd = 1.1 ± 0.1 μM), and this inhibition is sufficient to explain the observed antiviral activity.
LABOUR SUPPLY AND INCOME UNCERTAINTY: THE GEOMETRY OF A SPECIAL CASE

The effect of increased uncertainty on the agent's allocation decision is an intriguing general question and has recently received some systematic attention in the literature. Sandmo has analyzed the effect of savings rate uncertainty on the savings decision and both he and Leland have explored the effect of “income uncertainty” on the same decision. In addition, Leland has investigated the effects of uncertainty on optimal foreign exchange positions and both authors, Leland and Sandmo have begun an exploration of the effects of uncertain demand on the firm's output decision. Finally, Block and Heineke have analyzed the effect of income, savings rate, and wage uncertainty on the agent's labour allocation. However, in all of this work there has not been a geometric treatment of even a restricted case. The purpose of this note is to develop such an analysis for a special, but interesting labour allocation problem, and thereby derive the results of income uncertainty in a transparent fashion.
LKB1 is a Critical Regulator of Early Atrial Growth and Electrophysiological Function

The liver kinase B1 (LKB1)-AMP activated protein kinase (AMPK) pathway regulates cellular metabolism, polarity, and growth. Although previous studies have documented the maladaptive consequences of LKB1 deletion in the progressive development of atrial fibrillation (AF) and cardiac hypertrophy, its role in chamber-specific pathophysiology remains largely unresolved. Therefore we systematically explored LKB1's differential effects on structural and ion channel remodeling in mice with LKB1 deletion in cardiomyocytes. Atrial but not ventricular Nav1.5 and Cx40 expression levels were markedly downregulated in 1d neonates, giving rise to a 2-fold prolongation of the P wave on surface ECG. Detailed ex vivo optical action potential (AP) mapping studies revealed presence of marked inter-atrial conduction abnormalities, loss of bi-atrial electrical coupling, and prolonged AP durations in the atria of mice with LKB1 deletion. In contrast, ventricular changes developed with a much slower time-course that was consistent with previous studies. AMPK α2 inactivated hearts demonstrated modest overlap in ion channel expression, but retained normal ECG characteristics, cardiac structure and function compared to their LKB1 deleted counterparts. LKB1 deletion triggers a primary atrial electrophysiological remodeling program that precedes structural abnormalities and likely underlies the development of AF. LKB1 may be a novel target for the prevention of AF.
Enhanced terahertz emission from impurity compensated GaSb

We report femtosecond optically excited terahertz THz emission from tellurium doped GaSb at room temperature. The influence of the majority and minority carrier type and concentrations on the strength of the THz emission is investigated. Strong enhancement of THz emission in GaSb is observed as a result of compensation of native acceptors by tellurium donors. Surface field acceleration and the photo-Dember effect are identified as THz emission mechanisms in GaSb and modeled in dependence of the majority and minority carrier type and concentrations in our GaSb samples. THz emission from p-type GaSb is dominated by the photo-Dember effect whereas THz emission from n-type GaSb is dominated by surface field acceleration. The doping conditions under which THz emission is maximized are identified.
The Riboflavin Content of Milk as Influenced by Diet

Summary Experiments with cows, involving 460 determinations made over a period of 9 1 2 months, showed clearly that the riboflavin content of milk can be influenced only to a limited extent by the diet. When cows were transferred from pasture to a ration of natural feeds selected to be very low in riboflavin its content in the milk decreased about 25 per cent. Increasing the riboflavin intake 30 to 50 per cent by feeding a molasses-yeast byproduct caused only a temporary increase in the concentration of riboflavin in the milk. A winter ration consisting of good quality hay, acid grass silage and a grain mixture maintained the milk riboflavin at the pasture level. Goats fed a riboflavin-free purified diet continued to secrete large amounts of riboflavin in the milk, indicating this factor is not a dietary essential for lactation in the goat. No consistent difference was observed in the milk yield or the riboflavin concentration when the purified diet was supplemented with a molasses-yeast byproduct supplying riboflavin. Likewise, no advantage in milk secreted was noted between a thiamin-deficient purified diet and one adequate in it and other factors of the B-complex. The data from both cows and goats indicate that there is an inverse relation between the milk yield and the riboflavin concentration of the milk.
Genetic distance as a predictor of heterosis and hybrid performance within and between heterotic groups in sunflower.

Heterosis is significant for seed yield and is one of the driving forces behind the hybrid seed industry in cultivated sunflower (Helianthus annuus L). Heterotic groups in sunflower, if any other than the female and male inbred-line groups exist, have not been well studied or described. The primary aims of this study were to assess the utility and validity of a series of proposed heterotic groups and estimate correlations between genetic distance, heterosis, and hybrid performance for seed yield in sunflower. Fortytwo female by male heterotic group (A × R) and 81 female by female heterotic group (A × B) single-cross hybrids were grown in Corvallis, Ore., and Casselton, N.D., in 1996 and 1997. Heterosis was significant for seed yield and plant height but not for seed oil concentration and days to flowering. Genetic distances were significantly correlated with hybrid seed yield when estimated from AFLP fingerprints (GD) (r = 0.63 for A × R and 0.79 for A × B hybrids), but not from coancestries (GC) (r = -0.02 for A × R and 0.54 for A × B hybrids). GD (R2 = 0.4) was a poor predictor of hybrid seed yield. The proposed heterotic groups in sunflower seem to have utility, but do not seem to be as strongly differentiated as those in corn (Zea mays L.). The highest-yielding hybrids were from the BC× RB heterotic pattern; however, several BC× BC hybrids (within-group hybrids) were among the top-yielding hybrids. The outstanding performance of certain BC× BC hybrids casts some doubt on the validity of the BC group. Substantial genetic diversity seems to be present within and between heterotic groups in sunflower.
Morphological Comparisons of Insular and Mainland Populations of Southeastern White-Tailed Deer

External body measurements were compared among 123 mainland deer from both bottomland swamp and adjoining upland habitats in South Carolina, and 46 deer from a Georgia coastal barrier island. Island deer of both sexes were smaller in length and weight but had longer hair than mainland deer. Female deer from the mainland swamp habitat were smaller in length and weight and had shorter flank hair than females from nearby upland habitats. Male deer from the two mainland habitats showed no differences in either length or weight. Analyses of variance indicated that island deer of both sexes had proportionally smaller body circumferences than their mainland counterparts. Males from the two mainland habitats also differed, with those from the swamp having proportionally larger body circumferences and narrower distances between the eyes. Mainland females also had significantly larger proportional hind foot lengths than did island females. Discriminant function analyses indicated broad overlap among male deer from all three locations, whereas island females were clearly separable from females from the two mainland habitats, which broadly overlapped one another. Body circumference in the case of males and hind foot length in the case of females showed the highest correlations with the discriminant functions for differences between localities. Differences in body length and weight and hair length paralleled similar differences shown earlier for feral swine from the same island and mainland habitats. These similarities suggest that the differences observed are probably not the result of random genetic drift or founder effect.
Therapeutic Review: Terbinafine

al, U ard V Terbinafine is a synthetic allylamine antifungal used commonly in both human and veterinary medicine. Terbinafine inhibits squalene epoxidase, a key enzyme in ergosterol biosynthesis,1-4 thereby decreasing ergosterol synthesis and causing toxic levels of squalene to accumulate in the fungal cell. Without ergosterol, the cell wall is weakened; this leads to increased cellular permeability and increased squalene levels that are directly toxic to the cells. Because of these mechanisms of action, terbinafine has both fungistatic and fungicidal properties.1,4 Moreover, through experimental investigations, terbinafine has shown anticancer and antiangiogenic actions in several neoplastic cell lines, and free radical scavenging properties in vitro.5-7 Several preparations of terbinafine are commercially available in the United States, including 250-mg oral tablets (Lamisil; Novartis Consumer Health, Summit, NJ USA; Terbinex; Innocutis Holdins LLC, Charleston, SC USA), 125and 187.5-mg oral granules (Lamisil, Novartis Consumer Health), and several topical creams and gels containing 1% terbinafine hydrochloride (Lamisil AT Cream, Lamisil AT Gel, Lamisil AT spray, Novartis Consumer Health). Other formulations are being developed, most notably a carrier-based liquid spray that delivers 15 mg/mL terbinafine in Transferomes directly to the nail bed (TDT 067; Celtic Pharma Management LP, Hamilton, Bermuda).8 Additional studies are evaluating transdermal iontophoretic delivery of terbinafine.9 Terbinafine is well absorbed via the oral route and its absorption is not dependent on the presence of food.1 Interestingly, in red-tailed hawks (Buteo jamaicensis) and African penguins (Spheniscus demersus), a biphasic absorption pattern is present.10,11 Mean maximum plasma concentrations of terbinafine occur at approximately 2 hours in humans, horses (Equus ferus caballus), and penguins, and 3 to 5 hours after administration in red-tailed hawks.1,10-12 In a scientific study
A cortical substrate for memory-guided orienting in the rat

Anatomical, stimulation, and lesion data have suggested a homology between the rat frontal orienting fields (FOF) (centered at +2 AP, ±1.3 ML mm from Bregma) and primate frontal cortices such as the frontal or supplementary eye fields. We investigated the functional role of the FOF using rats trained to perform a memory-guided orienting task, in which there was a delay period between the end of a sensory stimulus instructing orienting direction and the time of the allowed motor response. Unilateral inactivation of the FOF resulted in impaired contralateral responses. Extracellular recordings of single units revealed that 37% of FOF neurons had delay period firing rates that predicted the direction of the rats' later orienting motion. Our data provide the first electrophysiological and pharmacological evidence supporting the existence in the rat, as in the primate, of a frontal cortical area involved in the preparation and/or planning of orienting responses.
DIRECT PLACEMENTS (Discussion)

MR. CONKLIN'S PAPER builds upon and extends the analyses of direct placement made in the other three leading studies of recent years which are referred to by him: the article by Harold Fraine of the University of Wisconsin, published in the Journal of the American Association of University Teachers of Insurance in March, I949; the paper by Frazer Wilde of the Connecticut General Life Insurance Company, which appears in the I950 Proceedings of the American Life Convention; and the article by Raymond Corey of Harvard University in the November, I950, issue of the Harvard Business Review. I shall comment briefly on only a few of the points dealt with in one or more of these four papers. All four writers agree that the costs of flotation are less iii direct placement than in a public offering. Mr. Conklin has gone farther than the others in attempting to quantify the savings in direct placement and the possible allocation of these savings. On the basis of limited data, he concludes that the reduction in flotation costs can be expressed as a saving in effective interest cost of from three to six yield basis points, with the probable average closer to three than six, especially in the case of large public utility issues. Thus, if a borrower could sell publicly a bond issue at a price that would give it a cost of 3.00 per cent after payment of flotation costs, it could reduce its cost to 2.97 per cent by a direct placement, if it could be sure of obtaining as high a price in a direct placement as in a public sale. There are two elements in this contingency. In the first place, to what extent are the lender's costs greater in a direct placement than in the purchase of an issue from an underwriter and how far, therefore, must the lender lower its bid price to cover these additional costs? Secondly, to what extent will bargaining and alternative sources of funds affect the distribution of the savings of direct placement between borrower and lender? Mr. Conklin has considered the latter of these questions in some detail-; the former he has touched upon only lightly. With respect to the first of these questions, an insurance company might find that it cost enough more to make a direct loan so that it would be required, if it insisted on recovery of its costs, to lower its
Reflectivity studies of Ti- and Ta-dichalcogenides: Phonons

Abstract The i.r.-spectra of the 1T phases of TiS2, TiSe2, TaS2 and TaSe2 reveal features attributed to large free carrier densities and to i.r.-active longwavelength phonons. We find a single phonon in TiS2, TiSe2 and TaS2, but six phonons in TaSe2, The oscillator strengths are significantly higher in the Ti-compounds yielding large values of the infrared effective charge, ∼6e, and electron-phonon coupling constant, 0.4–1.0. The observation of many modes in TaSe2 is attributed to a superlattice distortion driven by a charge density wave.
Engineering Approach for the Evaluation of Mechanical Wear Considering the Experimental Holloman High-Speed Test Track

AbstractThis research is directed toward an understanding of the high-speed interaction effects that two bodies have on each other. The experimental high-speed test track at Holloman AFB has undergone many design innovations over 50 years. One of the problems that remains in the modern era related to improving the speed characteristics of a rocket test sled is the wear that the interconnecting device, called the slipper, undergoes as it slides down the rail and impacts local asperities. The research is separated into two main areas. The first is the metallurgical investigation in which the material change is brought about by the surface friction through surface collision, and characteristics are determined that lead to a numerical model. The second is the development of a finite-element model using the commercial code ABAQUS, which is used in an attempt to capture the physics involved in the overall phenomenon. It became evident that the wear is not uniform, but is dictated by the evolving aerodynamics of...
Activation of Gene Expression by a Ligand-induced Conformational Change of a Protein-DNA Complex

IlvY protein binds cooperatively to tandem operator sites in the divergent, overlapping, promoter-regulatory region of the ilvYC operon of Escherichia coli. IlvY positively regulates the expression of the ilvC gene in an inducer-dependent manner and negatively regulates the transcription of its own divergently transcribed structural gene in an inducer-independent manner. Although binding of IlvY protein to the tandem operators is sufficient to repress ilvYpromoter-specific transcription, it is not sufficient to activate transcription from the ilvC promoter. Activation ofilvC promoter-specific transcription requires the additional binding of a small molecule inducer to the IlvY protein-DNA complex. The binding of inducer to IlvY protein does not affect the affinity of IlvY protein for the tandem operator sites. It does, however, cause a conformational change of the IlvY protein-DNA complex, which is correlated with the partial relief of an IlvY protein-induced bend of the DNA helix in the ilvC promoter region. This structural change in the IlvY protein-DNA complex results in a 100-fold increase in the affinity of RNA polymerase binding at theilvC promoter site. The ability of a protein to regulate gene expression by ligand-responsive modulation of a protein-DNA structure is an emerging theme in gene regulation.
User experiences with clinical social franchising: qualitative insights from providers and clients in Ghana and Kenya

Background Clinical social franchising is a rapidly growing delivery model in private healthcare markets in low- and middle-income countries. Despite this growth, little is known about providers’ perceptions of the benefits and challenges of social franchising or clients’ reasons for choosing franchised facilities over other healthcare options. We examine these questions in the context of three social franchise networks in Ghana and Kenya.
RBP38, a Novel RNA-Binding Protein from Trypanosomatid Mitochondria, Modulates RNA Stability

We describe here the isolation and characterization of a novel RNA-binding protein, RBP38, from Leishmania tarentolae mitochondria. This protein does not contain any known RNA-binding motifs and is highly conserved among the trypanosomatids, but no homologues were found in other organisms. Recombinant LtRBP38 binds single and double-stranded (ds) RNA substrates with dissociation constants in the 100 nM range, as determined by fluorescence polarization analysis. Downregulation of expression of the homologous gene, TbRBP38, in procyclic Trypanosoma brucei by using conditional dsRNA interference resulted in 80% reduction of steady-state levels of RNAs transcribed from both maxicircle and minicircle DNA. In organello pulse-chase labeling experiments were used to determine the stability of RNAs in mitochondria that were depleted of TbRBP38. The half-life of metabolically labeled RNA decreased from ∼160 to ∼60 min after depletion. In contrast, there was no change in transcriptional activity. These observations suggest a role of RBP38 in stabilizing mitochondrial RNA.
High counting rate resistive-plate chamber

Parallel-plate avalanche chambers (PPAC) are widely used in physics experiments because they are fast (<1 ns) and have very simple construction: just two parallel metallic plates or mesh electrodes. Depending on the applied voltage they may work either in spark mode or avalanche mode. The advantage of the spark mode of operation is a large signal amplitude from the chamber, the disadvantage is that there is a large dead time (msec) for the entire chamber after an event. The main advantage of the avalanche mode is high rate capability 10{sup 5} counts/mm{sup 2}. A resistive-plate chamber (RPC) is similar to the PPAC in construction except that one or both of the electrodes are made from high resistivity ({ge}10{sup 10} {Omega}{center_dot}cm) materials. In practice RPCs are usually used in the spark mode. Resistive electrodes are charged by sparks, locally reducing the actual electric field in the gap. The size of the charged surface is about 10 mm{sup 2}, leaving the rest of the detector unaffected. Therefore, the rate capability of such detectors in the spark mode is considerably higher than conventional spark counters. Among the different glasses tested the best results were obtained with electron type conductive glasses, which obey Ohm`smore » law. Most of the work with such glasses was done with high pressure parallel-plate chambers (10 atm) for time-of-flight measurements. Resistive glasses have been expensive and produced only in small quantities. Now resistive glasses are commercially available, although they are still expensive in small scale production. From the positive experience of different groups working with the resistive glasses, it was decided to review the old idea to use this glass for the RPC. This work has investigated the possibility of using the RPC at 1 atm and in the avalanche mode. This has several advantages: simplicity of construction, high rate capability, low voltage operation, and the ability to work with non-flammable gases.« less
Metabolic Resource Allocation in Individual Microbes Determines Ecosystem Interactions and Spatial Dynamics

SUMMARY The interspecies exchange of metabolites plays a key role in the spatiotemporal dynamics of microbial communities. This raises the question of whether ecosystem-level behavior of structured communities can be predicted using genome-scale metabolic models for multiple organisms. We developed a modeling framework that integrates dynamic flux balance analysis with diffusion on a lattice and applied it to engineered communities. First, we predicted and experimentally confirmed the species ratio to which a two-species mutualistic consortium converges and the equilibrium composition of a newly engineered three-member community. We next identified a specific spatial arrangement of colonies, which gives rise to what we term the ‘‘eclipse dilemma’’: does a competitor placed between a colony and its cross-feeding partner benefit or hurt growth of the original colony? Our experimentally validated finding that the net outcome is beneficial highlights the complex nature of metabolic interactions in microbial communities while at the same time demonstrating their predictability.
CD4+ T Cells Are Required for the Development of Cytotoxic CD8+ T Cells During Mycobacterium tuberculosis Infection

The control of acute and chronic Mycobacterium tuberculosis infection is dependent on CD4(+) T cells. In a variety of systems CD8(+) T cell effector responses are dependent on CD4(+) T cell help. The development of CD8(+) T cell-mediated immune responses in the absence of CD4(+) T cells was investigated in a murine model of acute tuberculosis. In vitro and in vivo, priming of mycobacteria-specific CD8(+) T cells was unaffected by the absence of CD4(+) T cells. Infiltration of CD8(+) T cells into infected lungs of CD4(-/-) or wild-type mice was similar. IFN-gamma production by lung CD8(+) T cells in CD4(-/-) and wild-type mice was also comparable, suggesting that emergence of IFN-gamma-producing mycobacteria-specific CD8(+) T cells in the lungs was independent of CD4(+) T cell help. In contrast, cytotoxic activity of CD8(+) T cells from lungs of M. tuberculosis-infected mice was impaired in CD4(-/-) mice. Expression of mRNA for IL-2 and IL-15, cytokines critical for the development of cytotoxic effector cells, was diminished in the lungs of M. tuberculosis-infected CD4(-/-) mice. As tuberculosis is frequently associated with HIV infection and a subsequent loss of CD4(+) T cells, understanding the interaction between CD4(+) and CD8(+) T cell subsets during the immune response to M. tuberculosis is imperative for the design of successful vaccination strategies.
Issue Voting and Crime in Gubernatorial Elections

Objective. Research on gubernatorial elections has focused extensively on the impact of the economy, ignoring other noneconomic issues that voters may consider when casting their ballots. This article examines the impact of one such noneconomic issue, crime, to determine whether voters hold governors accountable for crime rates and, if so, whether they incorporate national- or state-level conditions. In addition, I investigate whether more educated segments of the electorate are likely to engage in issue voting. Methods. I empirically analyze these propositions using aggregate-level data on gubernatorial elections from 1986–2004. Results. The data analysis reveals that crime significantly influences gubernatorial races, voters consider state- rather than national-level conditions, and that crime rates have a larger impact in states with a more educated population. Conclusion. Future inquiries should explore other noneconomic issues at the national and subnational levels to determine the breadth of issues that impact elections.
New Directions in Counseling Women

A revolution in counseling women is one logical outcome of recent changes in the social, political, and economic movements that have predisposed individuals to modify their life-styles and value systems. This article discusses four facets of that revolution and concludes that new counselor training programs are required to meet the needs of emerging client populations. The conclusions are supported by research that indicates (a) new sources of knowledge about the development and functioning of women clients; (b) new groups of client populations whose needs are not being met by traditional counseling strategies; (c) innovative procedures specifically tailored to the unique characteristics of these client groups; and (d) revised standards of ethical practice to ensure competent and appropriate services for all client populations. Training programs are outlined that provide guidelines for sex-fair education for all counselors and more intensively focused training for counselors who select the counseling of women clients as a career specialty.
Association of Fibrinogen With Quantity of Coronary Artery Calcification Measured by Electron Beam Computed Tomography

Abstract —Increased plasma fibrinogen concentration is an independent risk factor for cardiovascular disease. Fibrinogen is the main coagulation protein in plasma, a determinant of blood viscosity, and can act as a cofactor for platelet aggregation. In this study of middle-aged men and women, we examined the association between plasma fibrinogen concentration and coronary artery calcification (CAC), a marker of preclinical coronary atherosclerosis. Two hundred twenty-eight participants were selected from the community-based Epidemiology of Coronary Artery Calcification Study, in which CAC was measured noninvasively by electron beam computed tomography. One hundred fourteen participants (57 men) were selected because they had high quantities of CAC; the remaining 114 participants (57 men) were selected because they had no detectable CAC. Logistic regression models were used to investigate the association between plasma fibrinogen concentration and high quantity of CAC. In men, an increase of 1 standard deviation in fibrinogen concentration was associated with a statistically significant odds ratio of 1.6 (95% CI 1.1 to 2.5) for a high quantity of CAC. In women, the corresponding odds ratio was 2.5 (95% CI 1.6 to 4.1). Inferences from sex-specific bivariate logistic models for odds ratios adjusted individually for each coronary risk factor and C-reactive protein were similar to those from the univariate models. In women, there was also a significant interaction between fibrinogen concentration and age. According to the models, younger women with high plasma fibrinogen were more likely to have high quantities of CAC than were younger women with low plasma fibrinogen. The strength of this association was diminished in older women.
Constitutive Activation of the Aromatic Hydrocarbon Receptor

The ligand-activated aromatic hydrocarbon receptor (AHR) dimerizes with the AHR nuclear translocator (ARNT) to form a functional complex that transactivates expression of the cytochrome P-450 CYP1A1 gene and other genes in the dioxin-inducible [Ah] gene battery. Previous work from this laboratory has shown that the activity of the CYP1A1 enzyme negatively regulates this process. To study the relationship between CYP1A1 activity and Ah receptor activation we used CYP1A1-deficient mouse hepatoma c37 cells and CYP1A1- and AHR-deficient African green monkey kidney CV-1 cells. Using gel mobility shift and luciferase reporter gene expression assays, we found that c37 cells that had not been exposed to exogenous Ah receptor ligands already contained transcriptionally active AHR-ARNT complexes, a finding that we also observed in wild-type Hepa-1 cells treated with Ellipticine, a CYP1A1 inhibitor. In CV-1 cells, transient expression of AHR and ARNT leads to high levels of AHR–ARNT-dependent luciferase gene expression even in the absence of an agonist. Using a green fluorescent protein-tagged AHR, we showed that elevated reporter gene expression correlates with constitutive nuclear localization of the AHR. Transcriptional activation of the luciferase reporter gene observed in CV-1 cells is significantly decreased by (i) expression of a functional CYP1A1 enzyme, (ii) competition with chimeric or truncated AHR proteins containing the AHR ligand-binding domain, and (iii) treatment with the AHR antagonist α-naphthoflavone. These results suggest that a CYP1A1 substrate, which accumulates in cells lacking CYP1A1 enzymatic activity, is an AHR ligand responsible for endogenous activation of the Ah receptor.
Mixed Methods and Credibility of Evidence in Evaluation

We argue for a view of credible evidence that is multidimensional in philosophical and methodological terms. We advocate for the importance of deepening the meaning of credible evaluation practice and findings by bringing multiple philosophical and theoretical lenses to the evaluation process as a basis for the use of mixed methods in evaluation, thus providing evaluators with strategies for garnering more complex and diverse perspectives on the creation of credible evidence. ©Wiley Periodicals, Inc., and the American Evaluation Association.
Induction of cellular glutathione and glutathione S-transferase by 3H-1,2-dithiole-3-thione in rat aortic smooth muscle A10 cells: protection against acrolein-induced toxicity

There is increasing evidence that aldehydes, including acrolein generated endogenously during the degradation process of biological molecules or the metabolism of foreign chemicals may be involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis. Because glutathione (GSH) and GSH S-transferase (GST) are a major cellular defense against the toxic effects of reactive aldehydes, in this study we have characterized the inducibility of GSH and GST by the unique chemoprotective agent, 3H-1,2-dithiole-3-thione (D3T) and their protective effects against acrolein-induced toxicity in rat aortic smooth muscle A10 cells. Incubation of rat aortic A10 cells with micromolar concentrations of D3T resulted in a concentration- and time-dependent induction of both GSH and GST. Treatment of A10 cells with D3T also led to induction of gamma-glutamylcysteine synthetase, the key enzyme involved in GSH biosynthesis. Notably, the levels of GSH and GST remained higher than basal levels 72 h after removal of D3T from the culture media. To examine the protective effects of D3T-induced GSH and GST against reactive aldehyde-mediated toxicity, A10 cells were pretreated with D3T and then exposed to acrolein. Pretreatment of A10 cells with D3T resulted in a marked decrease of acrolein-induced toxicity as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction assay and morphological changes. To further demonstrate the involvement of GSH and GST in protecting against acrolein-induced toxicity, buthionine sulfoximine (BSO) and sulfasalazine were used to inhibit cellular GSH biosynthesis and GST activity, respectively. Either depletion of cellular GSH by BSO or inhibition of cellular GST by sulfasalazine led to a marked potentiation of acrolein-induced toxicity in A10 cells. Furthermore, co-treatment of cells with BSO was found to greatly abolish the protective effects of D3T on acrolein-induced toxicity. Taken together, our results demonstrate for the first time that both GSH and GST in aortic smooth muscle cells can be induced by D3T, and that this increased cellular defense affords great protection against reactive aldehyde-induced cardiovascular cell injury.
Recent Advances in Vertex Detection

This talk reviews the recent advances in vertex detectors for high-energy colliders, focussing on CVD diamond as a radiation-hard alternative to silicon, the SLD 307-million-pixel tracking system, and the SVX-II detector in CDF.
Ontogeny of the Host Response to Enteric Microbial Infection

Normal newborn animals, including humans, do not have the discriminatory function of the fully mature form; as a result, they are more likely to have abnormal responses to food and commensal organisms. The development of this important function is intimately associated with changes in the intestinal immune system that occur during ontogeny in response to intrinsic genetic programs, exposure to food antigens, and colonization by a normal commensal flora. This chapter reviews what these changes are, when they take place, what mechanisms drive them, and how they contribute to the function of the mature response to enteric microbes, and also briefly describes the elements of the mature intestinal immune system. In the context of defense against microbial infection, an important function of intestinal epithelial cells is to act as a physical barrier. During gut ontogeny, lymphocyte populations develop in the human fetal intestine from about 11 weeks of gestation onward. The major changes after this period occur in the epithelial and lymphocyte populations. Antibiotic use in the neonatal period and infancy, which has significant effects on the intestinal flora and therefore on the maturation of the intestinal immune system, has also been associated with the subsequent development of allergic disease. Further study of the role of commensal-host interactions in guiding the maturation of intestinal immune function will provide added insight, not only into the responses that protect against enteric infections, but also into more general mechanisms involved in immunoregulation.
Current Use Of The Papanicolaou Smear

The Papanicolaou smear is an extremely useful screening technique for early detection of cervical neoplasia. The recent clarification of cervical intraepithelial neoplasia (CIN) as a continuum of dysplasia has ramifications for management. The modern reporting scheme includes a narrative portion that gives the clinician information beyond the original Class I–V. This is especially helpful in interpretation ofthe atypical smear. The recent findings of invasive disease following an atypical smear and the malignant potential of condylomatous changes have resulted in early use of colposcopy in these clinical situations. This article discusses Papanicolaou smear technique, reporting classifications, and management of the patient who has an abnormal smear.
Carbon tetrachloride injury of the liver; the protective action of certain compounds.

SummarySeveral agents were tested for protective action against carbon tetrachloride injury of the liver in rats. Marked protection was obtained with sodium thioglycollate, appreciable protection with glutathione, moderate protection with sodium thiomalate, and slight protection with cystein—all sulphydryl compounds. Sodium glycollate and sodium malate afforded protection comparable to their sulphydryl homologues. Methionine, and choline plus cystine did not afford protection. Other non-sulphydryl compounds, i.e., sodium thiosulphate, aspartic acid, glutamic acid, choline, and sodium acetate afforded no protection.A protective action against carbon tetrachloride injury of the liver in rats is not as closely related to the presence of -SH in the test agent as previously was observed for the protective action of certain compounds against hepatic injury by chloroform in the dog.