cssi/SciSciGPT-SciSciNet huggingface dataset:
Children and computers: new technology--old concerns.

Computer technology has ushered in a new era of mass media, bringing with it great promise and great concerns about the effect on children’s development and wellbeing. Although we tend to see these issues as being new, similar promises and concerns have accompanied each new wave of media technology throughout the past century: films in the early 1900s, radio in the 1920s, and television in the 1940s. With the introduction of each of these technologies, proponents touted the educational benefits for children, while opponents voiced fears about exposure to inappropriate commercial, sexual, and violent content. This article places current studies on children and computers in a historical context, noting the recurrent themes and patterns in media research during the twentieth century. Initial research concerning each innovation has tended to focus on issues of access and the amount of time children were spending with the new medium. As use of the technology became more prevalent, research shifted to issues related to content and its effects on children. Current research on children’s use of computers is again following this pattern. But the increased level of interactivity now possible with computer games and with the communication features of the Internet has heightened both the promise of greatly enriched learning and the concerns related to increased risk of harm. As a result, research on the effects of exposure to various types of content has taken on a new sense of urgency. The authors conclude that to help inform and sustain the creation of more quality content for children, further research is needed on the effects of media on children, and new partnerships must be forged between industry, academia, and advocacy groups.
Measurements and modeling of SiCl4 combustion in a low-pressure H2/O2 flame

Abstract Laser-induced fluorescence (LIF) was used to measure temperature and OH concentration profiles as a function of distance from a McKenna-style burner in premixed one-dimensional low-pressure H2/O2/Ar SiCl4-doped flames. The addition of SiCl4 was shown to affect the flame temperature and OH concentration profiles. A gas-phase chemical kinetics mechanism for the combustion of SiCl4 in an H2/O2/Ar flame was proposed, and experimental results were compared with predictions for a premixed one-dimensional laminar flame model based on CHEMKIN. The low-pressure flame data are sensitive to the overall kinetics of the mechanism. In order to obtain the best fit to the observed data for all flame configurations, we had to modify six different rates from our original estimates. None of the modified rates are well known for the temperature regime of our flame. Particle formation and surface chemistry were not taken into account.
Equity Theory: Directions for Future Research*

A review and critique of currently existing theories of equity or distributive justice lead to the conclusion that future theoretical development would be aided by a more complete analysis of the structural determinants of the activation of equity concerns as well as the conditions which lead to particular reactions to inequity. Explicit consideration is given to such determinants as the nature of the stratification system, the type of injustice involved, the existence of an ideology and sense of community, and the source of the inequity. Research specifying the impact of these conditions upon the emergence of equity concerns in social systems and subsequent collective or individual reactions to injustice should facilitate the reformulation and extension of equity theory.
Strabismus in Pediatric Pseudophakia

Objective To evaluate strabismus associated with pediatric pseudophakia. Design Retrospective case series. Participants Charts of 94 pediatric patients who underwent cataract extraction with primary intraocular lens implantation from 1990 to 2003 at Indiana University School of Medicine were reviewed. Only those patients who had pre–cataract extraction and post–cataract extraction alignment measurements were included. Methods Data were collected on gender, race, age at presentation, age at time of cataract surgery, and type of cataract. Pre–cataract extraction and post–cataract extraction data on visual acuity (VA), alignment, and amblyopia were recorded. Results of strabismus surgery were also evaluated. Main Outcome Measures Frequency, type and amount of strabismus, and results of strabismus surgery. Results Ninety-four pediatric pseudophakia patients were identified, and 37 (39%) had strabismus. Exotropia (46%) was more common than esotropia (41%). Factors not associated with the development of strabismus included age at presentation, interval between diagnosis and cataract extraction, race, and type of cataract. Factors statistically associated with the development of strabismus include pre–cataract extraction and post–cataract extraction VA, type of strabismus, and post–cataract extraction amblyopia. The mean pre–cataract extraction deviation of the group that had strabismus surgery was 22 prism diopters, and 75% were aligned at the last examination (mean follow up, 24 months). Conclusion Strabismus occurs more frequently in pseudophakic pediatric patients than in the general pediatric population. Pseudophakic children should be monitored carefully for the development of strabismus, which in many cases can be successfully treated.
Double-stranded DNA binding characteristics and subcellular distribution of a minor groove binding diphenyl ether bisbenzimidazole.

The interactions of Hoechst 33377 (H1) with 20 different oligomeric duplexes have been investigated via spectrofluorometric titrations and/or thermal denaturation experiments. H1 is shown to form 2:1 complexes with dsDNA binding sites of at least four contiguous A/T base pairs. H1 is also shown to possess the rare ability to meaningfully distinguish between different A.T rich sequences. For example, the combined equilibrium constants for complexation of the oligomeric duplex 5'-GCAATTGC-3' (15) by H1 are found to be 110-fold greater than for the duplex 5'-GCTTAAGC-3' (16). It is believed that the 5'-TpA-3' dinucleotide step in 16 disrupts the rigid "A-tract" conformation of 15 and discourages minor groove binding by agents capable of recognizing longer dsDNA sequences. Molecular models are presented which elucidate the structure of the (H1)(2)-dsDNA minor groove complex. The two H1 molecules bind to an A/T rich sequence of 6 bp in a slightly staggered, side-by-side, and antiparallel arrangement. Evidence suggests that the piperazine rings of the H1 side-by-side complex are capable of resting in the minor groove of G/C base pairs. Fluorescence microscopy studies using NIH3T3 cells indicate that H1 is capable of traversing the cytoplasmic membrane and selectively localizing to nuclear DNA. H1 also demonstrated the ability to inhibit endogenous transcription of the c-fos gene in NIH3T3 cells at micromolar concentrations. Cytotoxicity studies employing the same cell type show H1 to possess an LD(50) of 3.5 microM.
Zonal Method to Model Radiative Transport in an Optical Fiber Drawing Furnace

Precise modeling of radiative heat exchange between the furnace and the glass preform is a very important part of the modeling of the fiber drawing process in a high temperature furnace. Most earlier studies on this process have used the optically thick approximation, i.e., the radiative heat exchange is assumed to depend only on the preform surface temperature while the transmission, emission, and absorption within the preform are approximated as a diffusion process. The validity of this approximation in the modeling of the fiber drawing process is dubious since the diameter of the preform undergoes a drastic reduction during the drawing process. The objectives of this research are to use a more accurate approach-the zonal method-to replace the optically thick approximation for computing the radiative heat exchange between the furnace and the preform, and to determine if the optically thick approximation is valid for this process. In applying the zonal method, the preform surface is assumed to be diffuse to both transmission and reflection. An enclosure analysis is performed for the radiative exchange between the furnace and the outer surface of the preform and the zonal method is employed to consider the radiative exchange within the glass preform.
On the Welfare Effects of Eliminating Business Cycles

Abstract We investigate the welfare effects of eliminating business cycles in a model with substantial consumer heterogeneity. The heterogeneity arises from uninsurable and idiosyncratic uncertainty in preferences and employment, where, regarding employment, we distinguish among employment and short- and long-term unemployment. We calibrate the model to match the distribution of wealth in U.S. data and features of transitions between employment and unemployment. Unlike previous studies, we study how business cycles affect different groups of consumers. We conclude that the cost of cycles is small for almost all groups and, indeed, is negative for some. Journal of Economic Literature Classification Numbers: C68, D31, D61, E32.
Financial Management Grades for the States: A Prospective Use

This research examines whether financial management grades awarded to the states by the Government Performance Project (GPP) can provide some prospective gauge of fiscal performance in proximate years, particularly on the downside of the business cycle. Our findings confirm the weaker fiscal condition in both 2002 and 2003 of states that received lower financial management grades from the GPP in 2001, suggesting that these grades have the potential to be prospective as well as retrospective. These results, however, are tempered by several concerns that inform our suggestions for additional research to further assess the prospective potential of financial management performance grades.
Patterns of cytochrome oxidase inhibition by polycations.

1. The inhibition of cytochromec oxidase activity by three types of polycation (PL-3, PL-150 or 195, and salmine) § is described for three kinds of oxidase system: dispersed by Tween-80, detergent-free “soluble” oxidase, and particulate oxidase (submitochondrial particles). 2. Salmine acts as a competitive inhibitor towards cytochromec in all three systems, with aKi between 1 and 4μM. PL-3 (low M.W. polylysine) acts as a non-competitive inhibitor of oxidation in all three systems, with aKi of between 10 μM (submitochondrial particles) and 100 μM (detergrent-free oxidase). 3. PL-150 and PL-195, the high M.W. polylysines, act in three distinct ways, depending on the nature of the oxidase preparation: (a) as reversible competitive inhibitors, withKi of about 70 nM (with oxidase dispersed in Tween-80), (b) as stoichiometric inhibitors displaying pseudononcompetivie kinetics (with Keilin-Hartree submitochondrial particles), and (c) as “superstoichiometric” inhibitors, blocking up to 100 equivalents of oxidase, cytochromeaa3 (with detergent-free oxidase or with cholate-treated submitochondial particles). 4. PL-195 also inhibits NADH and succinate oxidase activities in intact butc-deficient submitochondrial particles; sigmoidal inhibition curves can be observed in such systems. The rate of PL-195 binding was of the order of 106M−1 sec−1 and the true binding constant between 0.1 and 0.01 nM for the systems showing high affinity. 5. High molecular weight polylysines may be useful in investigations of the topology and distribution of cytochromec binding sites on the mitochondrial membrane and in submitochondrial fragments and solubilized preparations. More than one oxidase molecule may be inhibited by one polymer molecule; submitochondrial fragments “opened” by cholate treatment may bind one polymer molecule to several surface sites; Keilin-Hartree particles, with a more “closed” configuration, sesm to bind one polymer molecule to a single site, suggesting a “ecrevice” structure.
Nontarget detectability and interference with parafoveal target identification.

Abstract A target and a flanking nontarget which shared no primary feature were exposed simultaneously in the parafoveal region of the left or right visual field. The presentation terminated with one of two metacontrast masks, one of which masked the nontarget significantly better than the other. One group of 8 subjects received nontargets which were detected better with one of the metacontrast masks, while another group of 8 subjects received nontargets which were detected better with the other mask. Target identification was significantly better when the nontarget appeared on its foveal side rather than on its peripheral side, and this superiority was independent of accuracy in detecting the nontarget. The lack of consistency of this result with models explaining the parafoveal identification asymmetry in terms of feature perturbations is emphasized. Asymmetric lateral inhibition is suggested as an explanation.
Chronic mechanical circulatory support: Rehabilitation, low morbidity, and superior survival

Abstract Because of donor scarcity, 12 (39%) of a series of 31 Novacor left ventricular assist system recipients required mechanical circulatory support for an average of 125 days before transplantation (range, 61 to 303 days). Ten received a heart transplant and all survived to discharge. Two died of infection before transplantation after 93 and 303 days of support. Significant reductions were noted from preimplantation values of right and left cardiac filling pressures. Right ventricular ejection fraction and cardiac index increased. The 4-month actuarial freedom from infection during support was 75%. Three patients benefited from chronic outpatient housing for 5, 18, and 131 days, respectively, with improvements in quality of life measures. Ten chronically supported patients participated in an intensive rehabilitative exercise program resulting in an improvement of New York Heart Association class from IV to I in 9 patients. Mean oxygen consumption, which was 10 mL · kg −1 · min −1 30 days after implantation (mean exercise time, 10 minutes) had risen to 15 mL · kg −1 · min −1 before transplantation (mean exercise time, 16 minutes). This series suggests that long-term circulatory support is compatible with low morbidity, significant physical and hemodynamic rehabilitation, and an outpatient setting.
Analgesia during at-home use of misoprostol as part of a medical abortion regimen

The objective of this study was to identify predictors of narcotic analgesic use during medical abortion. Two-thousand-seven-hundredforty-seven women with pregnancies of 63 days gestational age or less received 200 mg mifepristone followed by at-home use of 800 mg vaginal misoprostol in two consecutive clinical trials in the United States, and also reported their use of analgesics. Overall, 79% of these subjects used narcotic analgesics. Women in the 2nd of the two studies were randomized to use misoprostol 24, 48, or 72 h after mifepristone. Those who were randomized to 24 h were more likely to use narcotic analgesics than those who were randomized to 48 or 72 h. In both studies, the use of narcotic analgesia during medical abortion was less prevalent among parous women and Asian women, and among those with a gestational age of 56 days or less. The clinic providing care for the patient was the most important determinant of narcotic analgesia use, even though the analgesia was used at home. Use of narcotic analgesics in these women undergoing medical abortion at home was more prevalent than use reported in previous studies where women underwent medical abortion in a clinical setting. © 2001 Elsevier Science Inc. All rights reserved.
1019-29 Resection vs PTFE Chordal Replacement for Repair of Mitral Valve Insufficiency

Traditional management of prolapsing leaflets involves leaflet resection ± native chordal repair. Uncertainty exists as to the role of chordal replacement with PTFE sutures. We compared the outcome of repair in 108 pts, 56 (52%) with #5 PTFE chordae (C) and 52 (48%) with resection (R). Both C a R had Puig-Massana ring annuloplasties. Mean age was 61 ± 16 yrs, 53 were male (49%) and 79% of pts were NYHA III or IV. Sinus rhythm was present in 75 (69%) pts, atrial fibrillation in 25 (23%). Etiology was myxomatous: 68 (63%). rheumatic: 13 (12%) ischemic: 12 pts (11%). Other valve replacement ± CAB were performed in C 16 (29%) pts, R 27 (52%) (p = 0.0132). Clamp time was 56 ± 23 min. for C, 61 ± 28 min for R (p = NS). bypass time 78 ± 30 and 84 ± 30 min (p = NS). Mortality (30 day) was CR 1/56 (1.8%), R 3/52 (5.8%) (p = NS). Post-op, mitral regurgitation was absent/mild in 104 (96%) pts, for CR 53 (95%), R 51 (98%) (p = NS). Predischarge mitral valve gradient was for CR, 2.45 ± 1.78 mm and RT 2.73 ± 2.45 mm (p = NS). At follow-up of up to 5 years, 96% of pts were NYHA I or II. Reoperation was required in C 1/56 (2%) R 4/52 (8%). p = NS. Thus use of C produced results similar to R. C repair can be used in all pts with mobile leaflets and mitral regurgitation, especially when both anterior and posterior leaflets are involved.
Molecular and functional mapping of EED motifs required for PRC2-dependent histone methylation

Polycomb group proteins represent a conserved family of developmental regulators that mediate heritable transcriptional silencing by modifying chromatin states. One Polycomb group complex, the PRC2 complex, is composed of several proteins, including the histone H3 lysine 27 (H3K27) methyltransferase enhancer of zeste homolog 2 and the WD-repeat protein embryonic ectoderm development (EED). Histone H3K27 can be monomethylated (H3K27me1), dimethylated (H3K27me2), or trimethylated (H3K27me3). However, it remains unclear what regulates the number of methyl groups added to H3K27 in a particular nucleosome. In mammalian cells, EED is present as four distinct isoforms, which are believed to be produced by utilizing four distinct, in-frame translation start sites in a common Eed mRNA. A mutation that disables all four EED isoforms produces defects in H3K27 methylation [Montgomery, N.D., Yee, D., Chen, A., Kalantry, S., Chamberlain, S.J., Otte, A.P. & Magnuson, T. (2005). The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation. Curr. Biol., 15, 942-947]. To assess the roles of individual EED isoforms in H3K27 methylation, we first characterized three of the four EED isoform start sites and then demonstrated that individual isoforms are not necessary for H3K27me1, H3K27me2, or H3K27me3. Instead, we show that the core WD-40 motifs and the histone-binding region of EED alone are sufficient for the generation of all three marks, demonstrating that EED isoforms do not control the number of methyl groups added to H3K27.
Cardiovascular effects of doxacurium chloride in isoflurane-anaesthetised dogs

SUMMARY The cardiovascular effects of doxacurium were studied in 6 isoflurane-anaesthetised dogs. Each dog was anaesthetised twice, receiving doxacurium (0.008 mg/kg bwt) or placebo iv. Dogs were ventilated to normocapnia. Heart rate, cardiac index, systolic, diastolic, and mean arterial blood pressures, stroke volume, pulmonary vascular resistance, pulmonary artery wedge pressure, systemic vascular resistance, and pulmonary arterial pressure were determined. Neuromuscular blockade was assessed using the train-of-four technique. After recording baseline values, dogs randomly received either doxacurium or placebo iv, and data were recorded at 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 min. At 120 min, dogs treated with doxacurium received edrophonium (0.5 mg/kg bwt iv) to antagonise neuromuscular blockade; dogs treated with placebos received saline iv. No statistically significant differences were detected after doxacurium compared to placebo. In both the doxacurium and placebo groups, significant increases in systolic arterial blood pressure, cardiac index, and stroke volume and a significant decrease in systemic vascular resistance occurred with time. Doxacurium depressed twitch tension 100% in all dogs (time to maximal twitch depression, 11 ± 7 min). First twitch tension was less than 10% of baseline values in all dogs at the time (120 min) of edrophonium administration. Additional edrophonium (1.0 ± 0.4 mg/kg iv) was required to obtain a fourth twitch to first twitch ratio of greater than 0.70. In conclusion, doxacurium is a long-acting neuromuscular blocking agent with no significant cardiovascular effects in isoflurane-anesthetised dogs. In dogs, doxacurium is indicated primarily for long surgical procedures requiring neuromuscular blockade and cardiovascular stability.
The Relative Efficacy of Six Selective Media in Isolating Coagulase Positive Staphylococci from Meats

Summary Coagulase positive staphylococci were found in 30% of 236 meats when egg yolk agar was used, in 22% of 45 meats when mannitol-sorbic acid broth was used, in 16% of 70 meats when mannitol-salt agar was used, in 21% of 146 meats when tellurite-glycine agar was used, in 8% of 75 meats when polymyxin agar was used and in 7% of 54 meats when Vogel and Johnson agar was used. Of a total of 855 suspect colonies tested from the five solid media, 245 (29%) were coagulase positive. All of the media showed higher percentages of recovery from meats that contained relatively large numbers of staphylococci in proportion to the total number of cocci. The simultaneous use of egg yolk agar and mannitol-sorbic acid medium gave the best results.
The green ribbon: Multiscale physical control of phytoplankton productivity and community structure over a narrow continental shelf

Chlorophyll concentration, phytoplankton biomass, and total and nitrate-fueled primary productivity increase toward the coast over the 12-km-wide continental shelf of the southern portion of the Southern California Bight. These gradients are accompanied by changes in phytoplankton community composition: the outer shelf is characterized by offshore assemblages including pelagophytes and oligotrophic Synechococcus ecotypes while the inner shelf is dominated by diatoms, coastal Synechococcus ecotypes, and the picoeukaryote Ostreococcus. Across the small horizontal scale of the shelf, large changes in the vertical distribution and flux of nitrate maintain elevated productivity, driving variability in the vertical distribution of biomass and the integrated biomass and productivity of the entire shelf. Temporal variability from hours to days in chlorophyll fluorescence as measured by an autonomous profiling vehicle demonstrates that phytoplankton respond vigorously and rapidly to physical variability. The interaction of physical processes at different temporal and spatial scales is responsible for the observed biological gradients. These dynamics include: (1) vertical shear in the alongshore currents, (2) local wind forcing, (3) the internal tide, and (4) remote, large-scale variability. Individually, these mechanisms rarely or never explain the phytoplankton community composition and metabolic rate gradients. These results and a reanalysis of historical data suggest that monitoring thermal stratification at the shelf break and the tilt of the thermocline across the shelf will augment our ability to predict phytoplankton productivity, community composition, and biomass, thereby improving our understanding of fisheries dynamics and carbon cycling in the coastal ocean.
Gene Therapy in the Treatment of Heart Failure

Heart failure is a major cause of morbidity and mortality in contemporary societies. Although progress in conventional treatment modalities is making steady and incremental gains to reduce this disease burden, there remains a need to explore new and potentially therapeutic approaches. Gene therapy, for example, was initially envisioned as a treatment strategy for inherited monogenic disorders. It is now apparent that gene therapy has broader potential that also includes acquired polygenic diseases, such as heart failure. Advances in the understanding of the molecular basis of conditions such as these, together with the evolution of increasingly efficient gene transfer technology, has placed congestive heart failure within reach of gene-based therapy.
Stochastic Modeling of TCP/IP over Random Loss Channels

An analytical framework for modeling the performance of a single TCP session in the presence of random packet loss is presented that is based on a semi-Markov model for the window size evolution. The model predicts the throughput for LANs/WANs (low and high bandwidth-delay products) with good accuracy, as compared against simulation results with ns simulator. Generally, higher speed channels are found to be more vulnerable to random loss than slower channels, especially for moderate to high loss rates.
Pneumocystis carinii karyotypes.

Pulsed-field gel electrophoresis techniques were used to examine the chromosomes of Pneumocystis carinii isolated from laboratory rats and two human subjects. P. carinii organisms isolated from each of four rat colonies and from two patients each produced a distinct band pattern, but in all cases the bands ranged in size from 300 to 700 kilobase pairs. P. carinii from three rat colonies produced patterns containing 15 prominent bands. Of these 15 bands, 2 stained more intensely than would be expected of bands of their size, suggesting that the P. carinii haploid genome contains 17 to 19 chromosomes. Summing the molecular sizes of the bands and accounting for staining intensities suggested that the haploid genome of rat-derived P. carinii contains on the order of 10(7) base pairs. Human-derived P. carinii produced patterns containing 10 to 12 bands which appeared to be similar to the 15-band patterns seen in rat-derived P. carinii with respect to the size range of the bands. P. carinii from the fourth rat colony produced a more complex band pattern containing approximately 22 bands, most of which appeared to comigrate with the bands present in one of the 15-band P. carinii patterns, suggesting that these animals were simultaneously infected by two different varieties of P. carinii. Hybridization experiments using oligonucleotide probes specific for the P. carinii 18S rRNA gene supported this possibility. The band pattern of P. carinii derived from a given rat colony was generally stable over time. P. carinii band patterns were not strictly rat strain specific and appeared to be transferrable between animals housed in the same room. Images
Molecular Genetics of Nephronophthisis and Medullary Cystic Kidney Disease

Nephronophthisis (NPH) and medullary cystic kidney disease (MCKD) constitute a group of renal cystic diseases that share the macroscopic feature of cyst development at the corticomedullary border of the kidneys. The disease variants also have in common a characteristic renal histologic triad of tubular basement membrane disintegration, tubular atrophy with cyst development, and interstitial cell infiltration with fibrosis. NPH and, in most instances, MCKD lead to chronic renal failure with an onset in the first two decades of life for recessive NPH and onset in adult life for autosomal dominant MCKD. There is extensive genetic heterogeneity with at least three different loci for NPH (NPHP1, NPHP2, and NPHP3) and two different loci for MCKD (MCKD1 and MCKD2). Juvenile nephronophthisis, in addition, can be associated with extrarenal organ involvement. As a first step toward understanding the pathogenesis of this disease group, the gene (NPH1) for juvenile nephronophthisis (NPH1) has been identified by positional cloning. Its gene product, nephrocystin, is a novel protein of unknown function that contains a src-homology 3 domain. It is hypothesized that the pathogenesis of NPH might be related to signaling processes at focal adhesions (the contact points between cells and extracellular matrix) and/or adherens junctions (the contact points between cells). This hypothesis is based on the fact that most src-homology 3-containing proteins are part of focal adhesion signaling complexes, on animal models that exhibit an NPH-like phenotype, and on the recent finding that nephrocystin binds to the protein p130(cas), a major mediator of focal adhesion signaling.
Prevalence of Testicular Size Discrepancy in Infertile Men With and Without Varicoceles

Objectives To compare the frequency of testicular size discrepancy between infertile men with and without varicoceles. Methods The records of adult patients presenting for male infertility evaluations were examined. The testicular volumes and presence or absence of varicocele and varicocele grade were recorded. Testicular size discrepancy was defined as a testicular size difference of at least 4 mL. Results Of the 3927 men presenting for male infertility evaluation, 3202 met the inclusion criteria of the study. A total of 705 patients (22%) had testicular size discrepancy and 1105 presented with a varicocele (34%). Testicular size discrepancy was found to be more common in patients with any varicocele than in patients with no varicocele (32% vs 17%; P P Conclusions Testicular size discrepancy is approximately 2 times more common in infertile men with varicoceles than in men without varicoceles. Testicular size discrepancy with a smaller left testicle is more common than size discrepancy with a smaller right testicle, regardless of the side of the varicocele.
Economic Education Research: Part I, Issues and Questions

Becker, the Journal's new editor for research, summarizes where the profession stands in its quest to understand how students learn economics and emphasizes the need for more adequate models to use in measurement and research. This is the first of several short articles on this topic.
French Constitutionalism and the Administrative State: A Comparative Textual Study

This article examines the relationships between constitutionalism and public administration through a comparative textual analysis of the constitutions of the Fifth French Republic and the United States. Particular emphasis is placed on the exceptional powers of the presidents of the two countries, the influence of the executive power on the respective legislative processes, and the practical significance of the divided executive power in France compared to the formally unified American executive. These diverse comparisons are brought together by the theme of how the constitutional traditions in the two countries both promote and inhibit the capacity for action of the administrative state.
Colon and Endometrial Cancers With Mismatch Repair Deficiency Can Arise From Somatic, Rather Than Germline, Mutations

Background & Aims Patients with Lynch syndrome carry germline mutations in single alleles of genes encoding the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2; when the second allele becomes mutated, cancer can develop. Increased screening for Lynch syndrome has identified patients with tumors that have deficiency in MMR, but no germline mutations in genes encoding MMR proteins. We investigated whether tumors with deficient MMR had acquired somatic mutations in patients without germline mutations in MMR genes using next-generation sequencing. Methods We analyzed blood and tumor samples from 32 patients with colorectal or endometrial cancer who participated in Lynch syndrome screening studies in Ohio and were found to have tumors with MMR deficiency (based on microsatellite instability and/or absence of MMR proteins in immunohistochemical analysis, without hypermethylation of MLH1 ), but no germline mutations in MMR genes. Tumor DNA was sequenced for MLH1 , MSH2 , MSH6 , PMS2 , EPCAM , POLE, and POLD1 with ColoSeq and mutation frequencies were established. Results Twenty-two of 32 patients (69%) were found to have 2 somatic (tumor) mutations in MMR genes encoding proteins that were lost from tumor samples, based on immunohistochemistry. Of the 10 remaining tumors 3 had one somatic mutation in a MMR gene, with possible loss of heterozygosity that could lead to MMR deficiency, 6 were found to be false-positive results (19%), and 1 had only one mutation in a MMR gene and remained unexplained. All of the tumors found to have somatic MMR mutations were of the hypermutated phenotype (>12 mutations/megabase); 6 had mutation frequencies >200/megabase, and 5 of these had somatic mutations in POLE , which encodes a DNA polymerase. Conclusions Some patients are found to have tumors with MMR defects during screening for Lynch syndrome, yet have no identifiable germline mutations in MMR genes. We found that almost 70% of these patients acquire somatic mutations in MMR genes, leading to a hypermutated phenotype of tumor cells. Patients with colon or endometrial cancers with MMR deficiency not explained by germline mutations might undergo analysis for tumor mutations in MMR genes to guide future surveillance guidelines.
Digital processing of affective signals

Affective signal processing algorithms were developed to allow a digital computer to recognize the affective state of a user who is intentionally expressing that state. This paper describes the method used for collecting the training data, the feature extraction algorithms used and the results of pattern recognition using a Fisher linear discriminant and the leave one out test method. Four physiological signals, skin conductivity, blood volume pressure, respiration and an electromyogram (EMG) on the masseter muscle were analyzed. It was found that anger was well differentiated from peaceful emotions (90%-100%), that high and low arousal states were distinguished (80%-88%), but positive and negative valence states were difficult to distinguish (50%-82%). Subsets of three emotion states could be well separated (75%-87%) and characteristic patterns for single emotions were found.
Dementia Care Management in an Underserved Community The Comparative Effectiveness of Two Different Approaches

Objectives: To compare the effectiveness and costs of telephone-only approach to in-person plus telephone for delivering an evidence-based, coordinated care management program for dementia. Methods: We randomized 151 patient–caregiver dyads from an underserved predominantly Latino community to two arms that shared a care management protocol but implemented in different formats: in-person visits at home and/or in the community plus telephone and mail, versus telephone and mail only. We compared between-arm caregiver burden and care-recipient problem behaviors (primary outcomes) and patient–caregiver dyad retention, care quality, health care utilization, and costs (secondary outcomes) at 6- and 12-months follow-up. Results: Care quality improved substantially over time in both arms. Caregiver burden, care-recipient problem behaviors, retention, and health care utilization did not differ across arms but the in-person program cost more to deliver. Discussion: Dementia care quality improved regardless of how c...
Training of child and adolescent psychiatry fellows in autism and intellectual disability

Patients with autism spectrum disorders and intellectual disability can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in autism spectrum disorder and intellectual disability, we surveyed training directors of child and adolescent psychiatry fellowship programs. On average, child and adolescent psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum disorder and intellectual disability, respectively. Training directors commonly reported that trainees see 1-5 patients with autism spectrum disorder or intellectual disability per year for outpatient pharmacological management and inpatient treatment. Overall, 43% of directors endorsed the need for additional resources for training in autism spectrum disorder and intellectual disability, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate.
ConservedPrimers 2.0: a high-throughput pipeline for comparative genome referenced intron-flanking PCR primer design and its application in wheat SNP discovery.

In some genomic applications it is necessary to design large numbers of PCR primers in exons flanking one or several introns on the basis of orthologous gene sequences in related species. The primer pairs designed by this target gene approach are called "intron-flanking primers" or because they are located in exonic sequences which are usually conserved between related species, "conserved primers". They are useful for large-scale single nucleotide polymorphism (SNP) discovery and marker development, especially in species, such as wheat, for which a large number of ESTs are available but for which genome sequences and intron/exon boundaries are not available. To date, no suitable high-throughput tool is available for this purpose. We have developed, the ConservedPrimers 2.0 pipeline, for designing intron-flanking primers for large-scale SNP discovery and marker development, and demonstrated its utility in wheat. This tool uses non-redundant wheat EST sequences, such as wheat contigs and singleton ESTs, and related genomic sequences, such as those of rice, as inputs. It aligns the ESTs to the genomic sequences to identify unique colinear exon blocks and predicts intron lengths. Intron-flanking primers are then designed based on the intron/exon information using the Primer3 core program or BatchPrimer3. Finally, a tab-delimited file containing intron-flanking primer pair sequences and their primer properties is generated for primer ordering and their PCR applications. Using this tool, 1,922 bin-mapped wheat ESTs (31.8% of the 6,045 in total) were found to have unique colinear exon blocks suitable for primer design and 1,821 primer pairs were designed from these single- or low-copy genes for PCR amplification and SNP discovery. With these primers and subsequently designed genome-specific primers, a total of 1,527 loci were found to contain one or more genome-specific SNPs. The ConservedPrimers 2.0 pipeline for designing intron-flanking primers was developed and its utility demonstrated. The tool can be used for SNP discovery, genetic variation assays and marker development for any target genome that has abundant ESTs and a related reference genome that has been fully sequenced. The ConservedPrimers 2.0 pipeline has been implemented as a command-line tool as well as a web application. Both versions are freely available at http://wheat.pw.usda.gov/demos/ConservedPrimers/ .
Design of the virtually integrated database management system and the X.500 directory service for the Human Genome Project

The data generated from the 15-year U.S. Human Genome Project (HGP) are currently stored and maintained in highly decentralized genome databases worldwide. There is no single standard for implementing the genome databases and no centralized access to them. That creates difficulty for users to locate the relevant genome data among those databases. To facilitate the searching and accessing of the relevant genome databases the paper proposes a model of a virtually integrated database system for the HGP. The proposed database system, based on the X.500 directory service and the client/server model, will provide central access to the decentralized databases through a single access protocol. The design of the directory information base (DIB) for the HGP and the functions and basic design of the client/server programs are discussed in detail. >
Perceiving the political landscape: ego biases in cognitive political networks

Recent studies have found that individuals tend to see themselves as more central in a network than they really are. This body of work has generally been done among small groups of <30 actors. Additionally, settings have usually been in a well-bounded social context focusing on friendship or work relations. Other related research has found links between activity and influence in a network and accurate knowledge of the network. This paper brings together these areas of research on bias and accuracy in the study of a moderate sized legislative political network involving legislators, agency heads, lobbyists, industry representatives, and agency and legislative staff. In a setting where accuracy in an understanding of the political landscape has important implications, the study finds variation in cognitive network bias is patterned with respect to social knowledge, centrality, and an actor’s status in the political network. © 2002 Elsevier Science B.V. All rights reserved.
The effect of nitrogen on competitive growth mechanisms of diamond thin films

The correlation between surface morphology and texture (distribution of crystal orientations) has been analyzed to determine how nitrogen provides a competitive growth advantage for the formation of 001 texture in diamond films. The film morphologies were measured using TappingMode@ atomic force microscopy. Corresponding texture studies were performed using X-ray diVraction with a four-circle goniometer to measure (111), (220) and (400) pole figures. Orientation distributions were generated from the pole figures, from which inverse pole figures were made to quantify how texture was aVected by process variables. After 2 h of growth, with and without nitrogen, similar textures were observed. With increasing time, nitrogen stimulates the growth of orientations between 001, 114, and 104. Without nitrogen, the majority orientation is 101 with a secondary component near 113. Examination of fracture surfaces indicates correlations with the observed texture and morphology changes. © 2000 Elsevier Science S.A. All rights reserved.
Stimulus-Dependent Translocation of κ Opioid Receptors to the Plasma Membrane

We examined the cellular and subcellular distribution of the cloned kappa opioid receptor (KOR1) and its trafficking to the presynaptic plasma membrane in vasopressin magnocellular neurosecretory neurons. We used immunohistochemistry to show that KOR1 immunoreactivity (IR) colocalized with vasopressin-containing cell bodies, axons, and axon terminals within the posterior pituitary. Ultrastructural analysis revealed that a major fraction of KOR1-IR was associated with the membrane of peptide-containing large secretory vesicles. KOR1-IR was rarely associated with the plasma membrane in unstimulated nerve terminals within the posterior pituitary. A physiological stimulus (salt-loading) that elicits vasopressin release also caused KOR1-IR to translocate from these vesicles to the plasma membrane. After stimulation, there was a significant decrease in KOR1-IR associated with peptide-containing vesicles and a significant increase in KOR1-IR associated with the plasma membrane. This stimulus-dependent translocation of receptors to the presynaptic plasma membrane provides a novel mechanism for regulation of transmitter release.
A History of the Dar`a-Haifa Branch of the Hijaz Railroad

A book review of Juni Mansur's Al-Khatt al-Hadidi al-Hijazi: Tarikh wa Tatawwur Qitar Dar`a-Haifa
A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a) that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL). The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month), 91.3 ± 3.1 (2 months), and 89.6 ± 1.6% (3 months). rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month), 78.9 ± 7.4 (2 months), and 81.2 ± 6.2% (3 months) transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month), 2.1 ± 0.8 (2 months), and 2.1 ± 0.7% (3 months)] by vascular delivery. Micro-dystrophin delivered by rAAV8 and rAAV6 through the femoral artery significantly improved tetanic force and protected against eccentric contraction. Mouse studies translated to the hindlimb of cynamologous macaques using a similar vascular delivery paradigm. rAAV8 carrying eGFP in doses proportional to the mouse (5 × 1012 vg/kg in mouse vs 2 × 1012 vg/kg in monkey) demonstrated widespread gene expression [medial gastrocnemius – 63.8 ± 4.9%, lateral gastrocnemius – 66.0 ± 4.5%, EDL – 80.2 ± 3.1%, soleus – 86.4 ± 1.9%, TA – 72.2 ± 4.0%. These studies demonstrate regional vascular gene delivery with AAV serotype(s) in mouse and non-human primate at doses, pressures and volumes applicable for clinical trials in children with DMD.
Exogenous surfactant changes the phenotype of alveolar macrophages in mice.

Alveolar macrophages are essential for the maintenance of surfactant homeostasis. We asked whether surfactant treatment would change alveolar macrophage number and whether the alveolar macrophage p...
Activation of the Glucocorticoid Receptor Is Associated with Poor Prognosis in Estrogen Receptor-Negative Breast Cancer

Estrogen receptor-negative (ER(-)) breast cancers have limited treatment options and are associated with earlier relapses. Because glucocorticoid receptor (GR) signaling initiates antiapoptotic pathways in ER(-) breast cancer cells, we hypothesized that activation of these pathways might be associated with poor prognosis in ER(-) disease. Here we report findings from a genome-wide study of GR transcriptional targets in a premalignant ER(-) cell line model of early breast cancer (MCF10A-Myc) and in primary early-stage ER(-) human tumors. Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) coupled to time-course expression profiling led us to identify epithelial-to-mesenchymal transition (EMT) pathways as an important aspect associated with GR activation. We validated these findings by carrying out a meta-analysis of primary breast tumor gene expression from 1,378 early-stage breast cancer patients with long-term clinical follow-up, confirming that high levels of GR expression significantly correlated with shorter relapse-free survival in ER(-) patients who were treated or untreated with adjuvant chemotherapy. Notably, in ER(+) breast cancer patients, high levels of GR expression in tumors were significantly associated with better outcome relative to low levels of GR expression. Gene expression analysis revealed that ER(-) tumors expressing high GR levels exhibited differential activation of EMT, cell adhesion, and inflammation pathways. Our findings suggest a direct transcriptional role for GR in determining the outcome of poor-prognosis ER(-) breast cancers.
Mega2: data-handling for facilitating genetic linkage and association analyses

Summary: Mega2, the manipulation environment for genetic analysis, transparently allows users to process genetic data for family-based or case/control studies accurately and efficiently. In addition to data validation checks, Mega2 provides analysis setup capabilities for a broad choice of commonly used genetic analysis programs, including SimWalk2, ASPEX, GeneHunter, SLINK, SIMULATE, S.A.G.E., SOLAR, Vitesse, Allegro, PREST, PAP, Loki, Merlin and MENDEL. Availability: http://watson.hgen.pitt.edu/register/ Contact: dweeks@watson.hgen.pitt.edu Supplementary information: http://watson.hgen.pitt.edu/docs/mega2_html/mega2.html