cssi/SciSciGPT-SciSciNet huggingface dataset:
Prospects for applying genotypic selection of somatic oncomutation to chemical risk assessment

Genotypic selection methods detect rare sequence changes in populations of DNA molecules. These methods have been used to investigate the chemical induction of mutation and for the detection and diagnosis of cancer. The possible use of genotypic selection for improving current risk assessment practices is based on the premise that the frequency of somatic mutation is of critical importance in understanding and modeling carcinogenesis. If genotypic selection can measure the induction of specific mutations that disrupt normal cell/tissue homeostasis, then it could provide key mechanistic information for cancer risk assessment. For example, genotypic selection data might support a particular low-dose extrapolation method or characterize the relationship between rodent and human cancer risk. Strategies for evaluating the use of genotypic selection in cancer risk assessment include the concept of developing a battery of targets that detect a range of agent-specific effects. Ideal targets to examine by genotypic selection are the oncogene and tumor suppressor gene mutations frequently detected in human tumors because these are thought to represent tumor-initiating events. The most commonly occurring basepair (bp) substitutions within the ras and p53 genes are identified. Also, the battery of genotypic selection methods is defined in terms of the most important mutational specificities to include. In theory, the major basepair substitution mutations induced by 29 of 31 chemical carcinogens could be detected by analyzing three different mutations: G:C-->T:A, G:C-->A:T, and A:T-->T:A. Genotypic selection will have the greatest impact on risk assessment if measurement of spontaneous mutation is possible. Data from phenotypic selection assays suggest this corresponds to detection of mutant fractions of approximately 10(-7), and this would necessitate examining DNA samples containing >10(7) target molecules. Despite its apparent potential, considerable development and validation is needed before genotypic selection data can be applied to cancer risk assessment.
BINGE ALCOHOL CONSUMPTION IN ADOLESCENT AND ADULT MICE DIFFERENTIALLY REMODELS THE BRAIN TRANSCRIPTOME

Alcohol abuse in pre-teens and teenagers continues to be a considerable problem in the United States. Not only can brain injury result, but also several studies have now cemented the role of underage drinking in an approximate 5-fold increased risk for development of alcoholism. The mechanism by which the change in susceptibility occurs is not understood. Therefore, a mouse model of high alcohol consumption was utilized to further include the ability to test the consequences of differential drinking between adolescent and adult animals. Using genetically defined C57BL/6J x FVB/NJ F1 hybrid mice and a “Drinking in the Dark” (DID) protocol, we determined that young mice will drink more than their adult counterparts. Gene expression analysis by cDNA microarray hybridization of brain revealed significant differences in pathway regulation and an age-apparent left shift of overall transcription by alcohol. Over-represented transcription factor binding site usage following alcohol exposure was readily apparent in adult, but not adolescent brain. Epigenetic consequences were also uncovered. Chromatin immunoprecipitation (ChIP) analysis showed that alcohol changed the gene expression of Scn4b, a sodium channel beta subunit that modulates the kinetics of firing, through a mechanism involving the acetylation of histone H4. These findings indicate a clear age-related difference in brain transcriptome plasticity following binge alcohol drinking.
Panel methods for airfoils in turbulent flow

This paper describes how panel methods can be used to calculate the unsteady loading and radiated noise from airfoils in incompressible turbulent flow, while completely accounting for the mean flow distortion of the turbulence in the vicinity of the blade. Formulations based on the velocity and on the stagnation enthalpy are discussed. In three-dimensional flows, care must be taken with the velocity-based formulation to avoid singular behavior associated with vortex stretching by the mean flow. The velocity-based method is implemented in two dimensions to illustrate application of these methods, and is validated against Amiet's theory. Calculations showing the effect of blade thickness and angle of attack on the unsteady loading spectra are given. It is concluded that airfoil angle of attack has only a small effect on the unsteady loading, but that blade thickness reduces the spectral levels at high frequencies.
Improving Power Transfer Efficiency of a Short-Range Telemetry System Using Compact Metamaterials

Wireless power transfer using resonant inductive coupling has been employed in a number of applications, including wireless charging of electronic devices and powering of implanted biomedical devices. In these applications, power is transferred over short distances, which are much smaller (~ λ/100) than the wavelength of operation. In such systems, the power transfer efficiency of the link is inversely related to the range of operation. The power transfer efficiency is principally a function of the Q's of the individual coils and the coupling between them. In this paper, we demonstrate improvements in power transfer efficiencies using negative permeability metamaterials by increasing the mutual coupling between coils. A metamaterial slab is designed for operation at 27 MHz and is compact in size. The power transfer efficiency of the telemetry system in free space is compared to that in the presence of the metamaterial placed near one of the coils. The efficiency of the system increased in the presence of the metamaterial even as the free-space separation was held constant. This shows that compact negative permeability metamaterials can be used to increase power transfer efficiency of short-range telemetry systems used in various applications.
Teaming Up with Girl Scouts for Online Nutrition Information

Three librarians at LSU Health Shreveport partnered with staff members at the Shreveport service center of the Girl Scouts of Louisiana–Pines to the Gulf to teach girls about nutrition. The librarians provided instruction to the staff on healthelinks, MedlinePlus, and the other National Library of Medicine databases. They worked with the staff to incorporate these online resources into the nutrition curriculum for the Girl Scout leaders to use with their troops. They also provided two laptop computers, promotional items, and teaching aids. The program was repeated in the summer for week-long day camps designed to introduce girls to Scouting. The librarians had the opportunity to work directly with more than 100 girls at these camps to introduce them to authoritative, age-appropriate web sites on nutrition.
Regulation of mucin gene expression in human tracheobronchial epithelial cells by thyroid hormone.

We reported previously that the expression of the gene encoding MUC5AC mucin in human airway epithelial cells is controlled by retinoic acid via the retinoic acid receptor (RAR)-alpha and that 3,3',5-tri-iodothyronine (T(3)) inhibits the expression of MUC5AC. The purpose of the present study was to identify mechanisms mediating the effect of T(3). T(3) has been shown to inhibit gene expression via several mechanisms, either by enhancing or repressing the transcription of target genes or by the regulation of post-transcriptional events. Results showed that T(3) strongly inhibited MUC5AC-driven luciferase activity in normal human tracheobronchial epithelial cells that had been transiently transfected with a MUC5AC-luciferase reporter construct; however, it did not affect MUC5AC mRNA stability. These results indicate that T(3) suppresses MUC5AC expression at the transcriptional level. An analysis of deletion constructs showed that deletion of the region downstream of 3 kb resulted in markedly decreased levels of MUC5AC transcription in the absence of T(3) (i.e. under control conditions) as well as a loss of responsiveness to the inhibitory effects of T(3). This suggests that this region might contain elements important for the activation as well as the repression of MUC5AC transcription. To determine whether T(3) modulates retinoic-acid-dependent MUC5AC transcription via an alteration in the abundance of retinoid receptor proteins, we examined the type and abundance of these receptors in nuclear extracts of airway epithelial cells grown in the presence or absence of T(3). Western blots showed that T(3) markedly decreased several types of retinoid receptor while not affecting T(3) receptor proteins. Consistent with this finding were gel-shift assays revealing a decrease in RAR-retinoic acid response element complexes obtained from T(3)-treated cells. We propose that T(3) might inhibit retinoid-dependent MUC5AC expression by decreasing retinoid receptor levels and thereby decreasing the transcriptional activation of this gene for mucins.
Perforant Path Transection Induces Complement C9 Deposition in Hippocampus

The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells in affected brain regions during Alzheimer disease (AD) provided a basis for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs during AD. Immunostaining for C9, a key terminal component of the complement cascade membrane attack complex (MAC), showed extracellular C9 deposition in parenchyma around the EC wound and in hippocampus as early as 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, apoptotic EC layer II neurons were not immunostained by anti-rat C9 antibody, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was localized to the dentate gyrus middle molecular layer, a region of synaptic loss, dendritic degeneration, and early synaptogenesis. In addition, intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the MAC that is up-regulated in AD, was also detected in the wound area (extracellular), the dentate gyrus middle molecular layer (extracellular), and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participates in responses to brain injury, as well as in AD.
Sufficient and necessary conditions for routine deployment of user-centred design

The greatest challenge facing the HCI community is not the solution of any particular problem in the domain of human-computer interaction. Rather, it is the introduction of HCI practice into routine design of software products. Approaches to fostering the uptake of HCI solutions and, particularly, user-centred approaches to the design of software products have included education of designers and product managers, integration of user-centred design processes into software development processes and placement of HCI practitioners into development organisations. In practice, none of these approaches has proven successful. Software systems continue to be designed with little regard to their usage requirements and, consequently fail to meet their users' expectations. This paper exposes some of the problems associated with HCI-centric approaches to the deployment of user-centred design. It contrasts these with the approaches to deployment applied when the product of user-centred design, that is, ease of use of software products, is adopted as a business objective. These include not only the demand for a user-centred approach to design, but also the creation of organisations specifically structured to facilitate the uptake of user-centred design processes by product owners. (4 pages)
Discrimination of Bird and Insect Radar Echoes in Clear Air Using High-Resolution Radars

Abstract The source of clear-air reflectivity from operational and research meteorological radars has been a subject of much debate and study over the entire history of radar meteorology. Recent studies have suggested that bird migrations routinely contaminate wind profiles obtained at night, while historical studies have suggested insects as the main source of such nocturnal clear-air echoes. This study analyzes two cases of nocturnal clear-air return using data from operational Weather Surveillance Radar-1988 Doppler (WSR-88D) and X- and W-band research radars. The research radars have sufficient resolution to resolve the echo as point targets in some cases. By examining the radar cross section of the resolved point targets, and by determining the target density, it is found for both cases of nocturnal clear-air echoes that the targets are almost certainly insects. The analysis of the dependence of the echo strength on radar wavelength also supports this conclusion.
Rat bites: Fifty cases

A prospective study of 50 patients with uninfected rat bite wounds was undertaken to determine the natural incidence of wound infection without prophylactic antibiotics. All open wounds were cultured; bacterial isolates were cultured from 30% of wounds. Of bacterial isolates, 43% were Staphylococcus epidermidis and the remainder were Bacillus subtillus, diphtheroids, and alpha hemolytic Streptococcus. Only one patient (2%) developed an infection. Seventy-two percent of the bites occurred while the patient was sleeping, probably accounting for the fact that 84% of the wounds were on the exposed areas of the upper extremities and face. Treatment recommendations include good surgical management and avoidance of prophylactic antibiotics due to a low natural infection rate. If the wounds become infected, then a cephalosporin or penicillinase-resistant penicillin should be sufficient for treatment with appropriate surgical care of the wounds. Rabies prophylaxis usually is not required, but we suggest that tetanus prophylaxis is mandatory because most of our patients were deficient in this regard.
The surgical anatomy of the colorectal intramural blood supply

An experimental angiology study of 12 surgical colorectal specimens resected from 12 patients with colorectal malignancies in a prefixed state (panoramic view) and after fixation (cross-sectional views taken at 5 different segmental levels) was conducted in Newmarket General Hospital over a 6 month period. The angiology films were analysed quantitatively in order to study the surgical anatomy of the intramural blood supply with the aim of determining whether the arteriolar anastomotic pattern was variable, possibly making one part more suitable for anastomosis than others.The results revealed no difference in intramural vasculature at different lev els and the selection of any segment for colorectal anastomosis should be gov erned, so far as the blood supply is concerned, by the adequacy of the extramural circulation.
Association between physician volume and in-hospital mortality in patients with systemic lupus erythematosus.

Objective Systemic lupus erythematosus (SLE) is an uncommon, clinically complex disease for which prior experience treating similar patients may be particularly important. This study was undertaken to determine if physician volume is associated with the outcome of hospitalization of patients with SLE. Methods Data on in-hospital mortality in a population-based sample of 15,509 patients with SLE ages 18 years or older who were hospitalized in 2000, 2001, or 2002 in New York or Pennsylvania were obtained from state health planning agencies. Risks of in-hospital mortality were examined in relation to the average annual number of patients with SLE hospitalized by the admitting physician. Results Physician volume was inversely associated with mortality. Mortality was 4.1% among patients of physicians who treated 3 patients per year. After adjustment for demographic characteristics, severity of illness, and hospital characteristics, the mortality risk was 20% lower among patients in the middle category of physician volume (odds ratio 0.80, 95% confidence interval 0.66–0.96, P =0.02), and 42% lower among patients in the highest category of physician volume (odds ratio 0.58, 95% confidence interval 0.42–0.82, P = 0.002), compared with patients in the lowest category. The association was stronger among patients with nephritis (n = 2,673), for whom the adjusted odds of mortality were ∼60% lower among those in the highest category of physician volume. Conclusion Our findings indicate that higher disease-specific physician volume is associated with lower risks of in-hospital mortality in patients with SLE.
Cascade of the parametric decay instability in ionospheric heating experiments

A cascade of Langmuir waves excited by the O-mode radio waves in ionospheric heating experiments via the parametric decay instability (PDI) is studied. The threshold powers for each resonant and nonresonant cascade step are determined. The nonresonant cascade of mother Langmuir waves proceeds at the same location. However, each step of the resonant cascade occurs at a slightly different location so that the daughter wave can satisfy the local dispersion relation. In the resonance case the threshold power remains the same in each cascade. However, the mother Langmuir wave has to propagate downward to the resonant location of the daughter Langmuir wave for the next resonant cascade step. To compensate the propagation loss of the mother Langmuir wave, a large power ratio (∼10 dB) between two consecutive cascade lines in the observed HF wave enhanced plasma lines is required. The threshold powers for the nonresonant cascade steps are found to increase progressively as the cascade process proceeds. It is shown that the dependence of the threshold power on the step number N of the cascade for the nonresonant case is governed by ve/vi, where ve and vi, are the electron collision frequency and ion Landau damping rate, respectively. The threshold power has a N2 dependence for ve ≫ 2Nvi and a √N dependence for ve ≪ 2Nvi. It explains why the second cascade line hardly generates a third in early Tromso heating experiments and why more cascade steps can occur in Arecibo's heating experiments.
Two Xyloglucan Xylosyltransferases Catalyze the Addition of Multiple Xylosyl Residues to Cellohexaose

Xyloglucan (XyG) is the principal hemicellulose found in the primary cell walls of most plants. XyG is composed of a beta-(1,4)-glucan backbone that is substituted in a regular pattern with xylosyl residues, which are added by at least one and likely two or three xylosyltransferase (XT) enzymes. Previous work identified seven Arabidopsis thaliana candidate genes, one of which (AtXT1) was shown to encode a protein with XT activity (Faik, A., Price, N. J., Raikhel, N. V., and Keegstra, K. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7797-7802). We expressed both AtXT1 and a second closely related gene, now called AtXT2, in insect cells and demonstrated that both have XT activity for cellopentaose and cellohexaose acceptor substrates. Moreover, we showed that cellohexaose was a significantly better acceptor substrate than cellopentaose. Product structural characterization showed that AtXT1 and AtXT2 preferentially added the first xylosyl residue to the fourth glucosyl residue from the reducing end of both acceptors. Furthermore, when the ratio of UDP-xylose to cellohexaose and the reaction time were increased, both AtXT1 and AtXT2 added a second xylosyl residue adjacent to the first, which generated dixylosylated cellohexaose. On the basis of these results, we concluded that AtXT1 and AtXT2 have the same acceptor specificities and generate the same products in vitro. The implications of these results for understanding in vivo XyG biosynthesis are considered.
Characterization of fly ash from Israel with reference to its possible utilization

Abstract The demand for electricity in Israel is growing exponentially and is increasingly based on power generated from coal. Current means of ash disposal are both inadequate and wasteful and have reached their maximum potential, thus future ash disposal presents considerable economic and environmental problems. Two representative samples of coal fly ash from Israeli power plants were examined for their mineralogical, chemical, physical and technical properties. Both samples are good-quality type F fly ashes (ASTM nomenclature) with excellent pozzolanic characteristics. On the basis of strength index data, the South African fly ash was found to be a better pozzolan than the Colombian. A simple beneficiation process is suggested to produce a high-quality, reproducible and valuable raw material. Some specific uses for fly ash in the Israel context are suggested.
Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

Fluid flow has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load-induced bone remodeling. The objective of this study was to investigate the characteristics of flow-activated pathways. Previously we reported that fluid flow stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts. Here we demonstrate that flow-induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of flow stimulated a burst in NO production (8.2 nmol/mg of protein/h), while steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h). Both G-protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G-proteins stimulated dose-dependent NO release in static cultures of both calvarial osteoblasts and UMR-106 osteoblast-like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G-protein and calcium-dependent phase sensitive to flow transients, and a G-protein and calcium-independent pathway stimulated by sustained flow.
A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

Abstract Benign rolandic epilepsy (BRE) and Landau–Kleffner syndrome (LKS) are similar epilepsy syndromes with sleep-accentuated epileptiform activity, sporadic seizures, and language dysfunction. Levetiracetam has been associated with improved language function in LKS and seizure reduction in BRE. We hypothesized levetiracetam would improve language function in children with BRE. A pilot study was performed with six children (aged 6–12) with BRE and evidence of impaired auditory comprehension and verbal memory. Children were transitioned from their current anticonvulsant to 40 mg/kg/day levetiracetam over a 2-week period and retested at 6 months. At 6 months, three of four children with baseline auditory comprehension impairments performed normally (P = 0.06), and five had improved auditory verbal memory (P = 0.08). Seizures improved in five, decreasing from 2.7 to 1.0 seizure per 6 months (P = 0.11). Results from this pilot study suggest that levetiracetam may have a beneficial effect on language in children with BRE.
Experimental study of the production rate of pure enantiomers from racemic mixtures

Abstract Elution band profiles were determined experimentally for the racemic mixture of d - and l -mandelic acid on a bovine serum albumin chemically bonded phase. The results show significantly different profiles for a given amount of either isomer, whether pure or in the racemic mixture. The production rate at 99% purity is more than one order of magnitude higher under overlapping band than under touching band conditions. In the former instance, the recovery yield and production rate are always higher for the less retained enantiomer.
Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase from Lactobacillus gasseri.

Abstract Enolases are highly conserved metalloenzymes ubiquitous to cellular metabolism. While these enzymes share a large degree of sequence and structural similarity, they have been shown to possess a wide range of moonlighting functions. Recent studies showed that an enolase from Lactobacillus gasseri impedes the ability of Neisseria gonorrhoeae to adhere to epithelial cells. We present the crystal structure of this enolase, the first from Lactobacillus, with one of its Mg2+ cofactors. Determined using molecular replacement to 2.08 A, the structure has a flexible and surface exposed catalytic loop containing lysines, and may play a role in the inhibitory function.
Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α2-δ Protein

As part of a program aimed at generating compounds with affinity for the α2-δ subunit of voltage-gated calcium channels, several novel β-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the α2-δ subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood−brain barrier.
Estimating the probability that a simulated system will be the best

Consider a stochastic simulation experiment consisting of v independent vector replications consisting of an observation from each of k independent systems. Typical system comparisons are based on mean (long-run) performance. However, the probability that a system will actually be the best is sometimes more relevant, and can provide a very different perspective than the systems' means. Empirically, we select one system as the best performer (i.e., it wins) on each replication. Each system has an unknown constant probability of winning on any replication and the numbers of wins for the individual systems follow a multinomial distribution. Procedures exist for selecting the system with the largest probability of being the best. This paper addresses the companion problem of estimating the probability that each system will be the best. The maximum likelihood estimators (MLEs) of the multinomial cell probabilities for a set of v vector replications across k systems are well known. We use these same v vector replications to form vk unique vectors (termed pseudo-replications) that contain one observation from each system and develop estimators based on AVC (All Vector Comparisons). In other words, we compare every observation from each system with every combination of observations from the remaining systems and note the best performer in each pseudo-replication. AVC provides lower variance estimators of the probability that each system will be the best than the MLEs. We also derive confidence intervals for the AVC point estimators, present a portion of an extensive empirical evaluation and provide a realistic example. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 341–358, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10019
The importance of examining cohort uniqueness in the formulation of human investment policies

Abstract It is shown in this paper that the same single-period structure in relationships among schooling, experience, and earnings can have sharply contrasting meanings for life-cycle patterns. One of the observations may refer to a static economy in which expanding education at the higher levels brings diminishing marginal effects on national income, declining internal rates of return to investments in schooling and little learning in the post-school years. Yet exactly the same single-year age crosssection structure could reflect quite the opposite situation, with rising marginal social returns over successive cohorts, rising internal rates of return to the investments in higher education, and rising contributions of experience to productivity. This is the scenario of a dynamic economy in which investments in post-school human resource formation and in other inputs complementary with the services of well-educated people keep pace with the expansion in schooling. The contrast is not one of poor versus rich societies but of static versus dynamic ones. Policy implications in the two situations would be very different despite their identity in a conventional benefit-cost accounting.
Light propagation in moderately dense particle systems: a reexamination of the Kubelka-Munk theory.

A numerical method (NM) is developed to characterize radiative transfer in a moderately dense particle population, i.e., a suspension of concentration of <1–10% by volume. It assumes that the particles scatter in accord with the Mie equations, that the propagation of light over short distances is in accord with the exponential transmission law, and that the light flows in many (thirty-six) directions. For representative systems, predictions of the Kubelka-Munk theory (KMT) are compared with those of the NM; partial agreement is found. While this theory can be a useful tool, radiative transport in representative samples is found not to obey strictly either the assumptions for writing the basic differential equations of the KMT or those for solving them. The movement of diffuse light through an attenuating system is found to often collimate it, not to make it more diffuse as expected. This effect causes errors in absolute KMT predictions. New transport equations, like Schuster’s, with four parameters instead of two are written and solved to obtain some new KMT equations. Their predictions are compared with those of the NM.
A Single Unpaired and Transcriptionally Silenced X Chromosome Locally Precludes Checkpoint Signaling in the Caenorhabditis elegans Germ Line

In many organisms, female and male meiosis display extensive sexual dimorphism in the temporal meiotic program, the number and location of recombination events, sex chromosome segregation, and checkpoint function. We show here that both meiotic prophase timing and germ-line apoptosis, one output of checkpoint signaling, are dictated by the sex of the germ line (oogenesis vs. spermatogenesis) in Caenorhabditis elegans. During oogenesis in feminized animals (fem-3), a single pair of asynapsed autosomes elicits a checkpoint response, yet an unpaired X chromosome fails to induce checkpoint activation. The single X in males and fem-3 worms is a substrate for the meiotic recombination machinery and repair of the resulting double strand breaks appears to be delayed compared with worms carrying paired X chromosomes. Synaptonemal complex axial HORMA domain proteins, implicated in repair of meiotic double strand breaks (DSBs) and checkpoint function, are assembled and disassembled on the single X similarly to paired chromosomes, but the central region component, SYP-1, is not loaded on the X chromosome in males. In fem-3 worms some X chromosomes achieve nonhomologous self-synapsis; however, germ cells with SYP-1-positive X chromosomes are not preferentially protected from apoptosis. Analyses of chromatin and X-linked gene expression indicate that a single X, unlike asynapsed X chromosomes or autosomes, maintains repressive chromatin marks and remains transcriptionally silenced and suggests that this state locally precludes checkpoint signaling.
Hole pattern formation in unfired ceramic sheets by pulsed Nd:YAG laser

Single shot pulses from a Nd:YAG laser have been used to generate different sized holes and patterns in unfired ceramic sheets for electronic packaging applications. The single shot laser pulses were targeted using a computer controlled deflection system and a programmed pattern. With changes in pulse energy level and profile, the laser beam was also used to sinter line patterns in deposited thin and thick films. The surface radial temperature profile resulting from the laser pulse interaction was also directly mapped using a lacquer thermocoat. Effects of the laser pulse energy and beam spot size on laser/ceramic interactions, morphology, and structure of the drilled holes before and after sintering were examined by SEM. High quality hole patterns (of ∼100 μm hole size) were produced in unfired 100 μm thick ceramic sheets up to 100 μm thick using single shot of laser irradiation with 8 mJ pulse energy and 18 nsec pulse duration.
The dentition of the Indian Knoll skeletal population: Odontometrics and cusp number

Data on the permanent dentition of 153 individuals from the well known Indian Knoll skeletal population are presented. Mesiodistal and buccolingual measurements were taken with a Helios dial caliper. Cusp number of maxillary and mandibular molars was recorded. The Indian Knoll dentition is larger than many modern groups but smaller than Australoid or Mesolithic groups. With the exception of maxillary 12, males have larger teeth than females in both dimensions. The lower canine is the most dimorphic tooth. Through rank order correlation, an association was shown between the sexual dimorphism of the mesiodistal and buccolingual dimensions. Compared to modern groups, the Indian Knoll population displays a moderate degree of sexual dimorphism in tooth size. In general, the coefficients of variation were greater for the more distal teeth within morphological classes. Amounts of size variability did not differ significantly between the sexes; moreover, rank order correlations indicated that patterns of variability in both dimensions were similar for males and females. The predominant cusp number pattern for upper molars is 4-3-3 and for lowers, 5-5(4)-5. No sex differences were shown for cusp occurrence or bilateral asymmetry in cusp number.
Haploinsufficiency for Adrenomedullin Reduces Pinopodes and Diminishes Uterine Receptivity in Mice

Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein-coupled receptor when the receptor, called calcitonin receptor-like receptor (CL), is associated with a receptor activity-modifying protein 2 (RAMP2). We demonstrated previously that haploinsufficieny for each of these genes led to reduced maternal fertility, and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation, and fetal growth. Here, we further demonstrate that Adm(+/-) female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation, or fertilization. The poor fertility of Adm(+/-) female mice could not be rescued by transfer of wild-type blastocysts, which suggested an underlying defect in uterine receptivity. In fact, we found that Adm, Calcrl, and Ramp2 gene expressions are tightly and spatiotemporally regulated in the luminal epithelial cells of the uterus during the estrus cycle and the peri-implantation period. RAMP3, which also generates an AM receptor when associated with CL, had a diametrically opposite expression pattern than that of Adm, Calcrl, and Ramp2 and was most robustly induced in the stroma of the uterus. Finally, we discovered that Adm(+/-) female mice have a substantially reduced number of pinopodes on the uterine luminal epithelial surface, which is indicative and possibly causative of the poor uterine receptivity. Taken together, our studies identify a new class of pharmacologically tractable proteins that are involved in establishing uterine receptivity through the regulation of pinopode formation.
Mural propagation of descending vasa recta responses to mechanical stimulation.

To investigate the responses of descending vasa recta (DVR) to deformation of the abluminal surface, we devised an automated method that controls duration and frequency of stimulation by utilizing a stream of buffer from a micropipette. During stimulation at one end of the vessel, fluorescent responses from fluo4 or bis[1,3-dibutylbarbituric acid-(5)] trimethineoxonol [DiBAC4(3)], indicating cytoplasmic calcium ([Ca2+]CYT) or membrane potential, respectively, were recorded from distant cells. Alternately, membrane potential was recorded from DVR pericytes by nystatin whole cell patch-clamp. Mechanical stimulation elicited reversible [Ca2+]CYT responses that increased with frequency. Individual pericyte responses along the vessel were initiated within a fraction of a second of one another. Those responses were inhibited by gap junction blockade with 18 β-glycyrrhetinic acid (100 μM) or phosphoinositide 3 kinase inhibition with 2-morpholin-4-yl-8-phenylchromen-4-one (50 μM). [Ca2+]CYT responses were blocked by removal of extracellular Ca2+ or L-type voltage-gated channel blockade with nifedipine (10 μM). At concentrations selective for the T-type channel blockade, mibefradil (100 nM) was ineffective. During mechanostimulation, pericytes rapidly depolarized, as documented with either DiBAC4(3) fluorescence or patch-clamp recording. Single stimuli yielded depolarizations of 22.5 ± 2.2 mV while repetitive stimuli at 0.1 Hz depolarized pericytes by 44.2 ± 4.0 mV. We conclude that DVR are mechanosensitive and that rapid transmission of signals along the vessel axis requires participation of gap junctions, L-type Ca2+ channels, and pericyte depolarization.
Political Protest and Political Violence: A Nonrecursive Causal Model

This paper presents a nonrecursive causal model of violence at protest demonstrations; it seeks to account for violence by both the police and the protestors. The model is tested using data on 126 protest events in the United States. The results of the analysis suggest strongly that the outbreak of violence at protest demonstrations is the result of a dynamic process resulting from the interaction of police and protestors; exogenous variables are found to have little predictive power when the reciprocal causal link between protestor violence and police violence is included in the model. Political protest and political violence have become more frequent in the United States in the last fifteen years; correspondingly, they have come under increased scrutiny by social scientists during this period. Various theories have been proposed to account for both political protest and political violence, and to draw the links between them (Eisinger; Fogelson; Gurr; Lipsky; Lupsha; Muller; Schneider; Schumaker; Skolnick; Von Eschen et al.; Wilson). In this research note, I will examine empirically one small segment of the related questions of political protest and political violence: What accounts for the outbreak of violence at incidents of political protest?' The causal model described and tested below suggests that the outbreak of violence at protest events is, in part, a dynamic process. The analysis assesses the importance of a number of explanatory variables. Unlike a number of theories that view the outbreak of violence primarily as a psychological process (e.g., Gurr; Sears and McConahay), this model suggests that specific outbreaks of violence in settings of protest are primarily the result of events specific to the settings themselves. (For a similar view in a slightly different context, see McPhail; and Moinat et al.). Before turning to the model to be tested, I must define what is meant, for the purposes of this analysis, by political protest and point out an important distinction in the study of political protest. Political protest refers to "public group activity utilizing confrontation politics to apply stress to specific targets for the purpose of affecting public policy" (Terchek, 133). There are many other ways to define political protest but this is adequate for the analysis here. In looking at political protest, whether one is interested in explaining the impact of protest or what *The collection of data for this analysis was supported by NIMH grant No. 5 ROI MH 17421-02 SP, A. Paul Hare principal investigator. I would like to thank Dean MacCannell for making the data available. George Rabinowitz, Burdett Loomis, James Pierson, Michael Boss and several anonymous reviewers provided helpful comments on earlier drafts. Computer time was provided by Rice University, Indiana University, and the University of North Carolina; typing support was provided by the Departments of Political Science at Rice and Indiana Universities.
Poverty, Inequality, and Youth Violence

Recent school shooting incidents have served to highlight the social problem of lethal violence by young people in the United States. While many factors need to be considered, this article argues that broader social and economic forces such as poverty, inequality, and social exclusion shape most of the problem of youth violence in America. These structural factors tend to foster violence indirectly through their impact on the close-in institutions of the family, school, and community. Using the organizing concepts of social support and informal social controls, the article examines theory and research on the connections between economic inequality and social exclusion, the close-in institutions of family and community, and violent youth crime. It is argued that structural forces reduce the ability of families and communities to provide the social support and informal social control needed to prevent youth violence. Policy implications are briefly discussed.
Work Stress in the Family Life of African Americans

Researchers have documented how work outside of the home has an impact on family life. These effects are both positive and negative. The obvious positive effects are the income and social status it brings. Not as obvious, but still important, is identity. Work provides people with an important sense of identity. It is not uncommon that people invest themselves in their work identity and thus become publicly and privately known by the work they do (see Thoits, 1999, for a further discussion of identity). This helps to give meaning and a sense of coherence to life. The literature that has focused on work outside of the home has been primarily concerned with three aspects: (a) unemployment and economic hard times, (b) home-to-work stress contagion and spillover stress from work to the home, and (c) stressful work experiences in the workplace that are reflective ofjob-related characteristics. This third area is the focus of this article. By job-related stressors, we refer to demands of a particular job. These demands have been conceptualized as consisting of three aspects: physical demands; psychosocial demands; and job decision-making capac-
Adaptive control of multiplexed closed-circuit anesthesia

The design of an adaptive closed-circuit anesthesia controller based on a multiplexed mass spectrometer system is described. The controller deals with measurement deterioration caused by measurement delay and rise time through a long catheter as well as long sampling times due to the multiplexed measurements. Measurement data are extrapolated between sampling periods to increase the estimation convergence rate. A multiple-step-ahead predictive control algorithm is used to calculate intermediate control inputs between sampling intervals. Simulations are used to validate the designed controller. >
Error Estimates for a Finite Volume Element Method for Elliptic PDEs in Nonconvex Polygonal Domains

We consider standard finite volume piecewise linear approximations for second order elliptic boundary value problems on a nonconvex polygonal domain. Based on sharp shift estimates, we derive error estimations in H1-, L2- and L$_\infty$-norms, taking into consideration the regularity of the data. Numerical experiments and counterexamples illustrate the theoretical results.
Prolonged improvement of childhood onset systemic lupus erythematosus following systematic administration of rituximab and cyclophosphamide.

Background Although the combination of cyclophosphamide and rituximab has been utilized in case reports, there are no previous reports of the long term outcome of SLE treated systematically with this regimen. We report a pilot study to evaluate the efficacy of a systematically administered course of rituximab and cyclophosphamide over an eighteen month period to provide sustained improvement in childhood onset systemic lupus erythematosus (SLE).
A PARALLEL NEWTON-KRYLOV METHOD FOR ROTORCRAFT FLOWFIELD CALCULATIONS

This paper explores the use of Krylov subspace iterative methods for implicit solution of rotary-wing flowfields on parallel computers. A Newton-Krylov scheme is proposed which couples conjugate gradient-like iterative methods within the baseline structured-grid Euler/Navier-Stokes flow solver TURNS (Transonic Unsteady Rotor Navier Stokes). Two Krylov methods are studied, Generalized Minimum Residual (GMRES) and Orthogonal s-Step Orthomin (OSOmin). Preconditioning is performed with a parallelized form of the Lower Upper-Symmetric Gauss Seidel (LU-SGS) operator. The scheme is implemented on the IBM SP2 multiprocessor and applied to three-dimensi onal computations of a rotor in forward flight. The main benefit of the Newton-Krylov scheme is found to be a higher level of time-accuracy in implicit timestepping. This increases the allowable timestep for time-accurate unsteady calculations, yielding a reduction in the overall solution time.
Party Government and the United States

The lack of coherent, powerful, stable, responsible leadership in the national government of the United States is a source of mounting concern to serious students of American politics. So sober an analyst as Professor E. E. Schattschneider states "it is reasonable to suppose that the internal difficulties of the government will, sooner or later, if we do not overcome them, involve all of us in disaster." Quotations to a similar effect can be multiplied from observers in all walks of life. It is little short of surprising that a government that has successfully met the seemingly acid tests of the greatest war and the greatest depression in history should be considered so deficient in its very vitals. And yet a powerful case can be made for just this position despite our record of past achievement. That crises have been met and overcome the critic can hardly deny. What he may well maintain is twofold: one, that in our meeting of crises there has been too perilous a dependence on good fortune; and two, that the nature of the world today excludes any safe reliance on the methods of the past. The fate of the Third French Republic with its dependence on a Union SacrJe to produce strong government in time of need is a grim warning to those who still repose their confidence in inspired Presidential dictatorship. Robert Sherwood has recounted the anxious days before Pearl Harbor when even the perennial optimist Roosevelt well-nigh despaired of securing the power to avert the disaster his military staff foresaw. The sorry record of our China policy, set forth in the State Department's White Paper, lends impressive confirmation to Schattschneider's fear that expert knowledge is bootless when leaders lack power and courage to follow it. The spectacle of members of the House of Representatives privately denouncing a Rankin-led pension raid, but in the same breath confessing their inability to vote their convictions on a roll call, fills in the picture of a government dangerously deficient in responsible leadership. The golden age of isolation from world affairs and of an economy whose expansion seemed a gift of nature is gone. And the old easy-going assurance that somehow we will muddle through but measures the