cssi/SciSciGPT-SciSciNet huggingface dataset:
Interdependence of neural network dysfunction and microglial alterations in Alzheimer's disease-related models

Nonconvulsive epileptiform activity and microglial alterations have been detected in people with Alzheimer's disease (AD) and related mouse models. However, the relationship between these abnormalities remains to be elucidated. We suppressed epileptiform activity by treatment with the antiepileptic drug levetiracetam or by genetic ablation of tau and found that these interventions reversed or prevented aberrant microglial gene expression in brain tissues of aged human amyloid precursor protein transgenic mice, which simulate several key aspects of AD. The most robustly modulated genes included multiple factors previously implicated in AD pathogenesis, including TREM2, the hypofunction of which increases disease risk. Genetic reduction of TREM2 exacerbated epileptiform activity after mice were injected with kainate. We conclude that AD-related epileptiform activity markedly changes the molecular profile of microglia, inducing both maladaptive and adaptive alterations in their activities. Increased expression of TREM2 seems to support microglial activities that counteract this type of network dysfunction.
Implications for Child Abuse and Neglect Interventions from Early Educational Interventions

Family impoverishment as evidenced by low income, low educational levels, and unemployment is the strongest predictor of poor developmental outcomes for children. Two domains in particular, school failure and abuse and neglect, are highly associated with poverty and have been at the center of many prevention and intervention efforts during the past three decades. Separate groups and organizations, however, have worked independently to address these two concerns about children. Predictably, most of the attention to reducing school failure originated in the fields of education and child development, where the goals are to enhance children’s cognitive development and school performance. By contrast, the attention to reducing abuse and neglect derived from social services and health organizations, and aims to protect the child from further abuse and neglect, provide treatment and, more recently, develop prevention strategies. In addition to being influenced by different professions and different objectives for the child, these two areas of concern have also been characterized by different intervention procedures.
Gender Differences in Academic Achievement: Is Writing an Exception to the Gender Similarities Hypothesis?

ABSTRACTThe gender similarities hypothesis by J. S. Hyde (2005), based on large-scale reviews of studies, concludes that boys and girls are more alike than different on most psychological variables, including academic skills such as reading and math (J. S. Hyde, 2005). Writing is an academic skill that may be an exception. The authors investigated gender differences in academic achievement using a large, nationally stratified sample of children and adolescents ranging from ages 7–19 years (N = 2,027). Achievement data were from the conormed sample for the Kaufman intelligence and achievement tests. Multiple-indicator, multiple-cause, and multigroup mean and covariance structure models were used to test for mean differences. Girls had higher latent reading ability and higher scores on a test of math computation, but the effect sizes were consistent with the gender similarities hypothesis. Conversely, girls scored higher on spelling and written expression, with effect sizes inconsistent with the gender simi...
Defend against topological attacks in sensor networks

Sensor networks are vulnerable to many active attacks due to the defects of the network protocols that are not designed carefully to involve security defenses at the beginning. Most of the attacks try to cause topological distortion by spoofing or replaying routing information. This paper proposes to use a location-based naming (LBN) mechanism for sensor nodes, in which location information is embedded into node identifier and acts as an inherent node characteristic to provide authentication service in local access control. When LBN is enforced, the impacts of many attacks to sensor network topology can be limited in a small area. A link layer authentication (LLA) scheme is also proposed to further decrease the impacts of those attacks. Our LBN and LLA can be combined and act as an efficient solution against a wide range of topological attacks in sensor networks
Zapato: Automatic Theorem Proving for Predicate Abstraction Refinement

Counterexample-driven abstraction refinement is an automatic process that produces abstract models of finite and infinite-state systems. When this process is applied to software, an automatic theorem prover for quantifier-free first-order logic helps to determine the feasibility of program paths and to refine the abstraction. In this paper we report on a fast, lightweight, and automatic theorem prover called Zapato which we have built specifically to solve the queries produced during the abstraction refinement process.
Osmotic response of individual cells during freezing. II. Membrane permeability analysis.

Abstract An analytical model is presented to simulate the freezing of individual yeast cells. In addition the model is solved numerically on a digital computer to obtain values for cell volume as a function of temperature, based on the thermal protocol during freezing, and the transport parameters of the cell membrane. The numerical procedure was modified to enable values for the membrane hydraulic permeability reference coefficient, L pg , and activation energy, E L p , to be deduced by nonlinear analysis of complementary experimental data (10). It was observed that the apparent values of both L pg and E L p increase with cooling rate, from L pg = 0.0116 μm 3 μm −2 atm −1 min −1 and E L p = 19.4 kJ mol −1 for 9 °K/min to L pg = 2.11 μm 3 μm −2 atm −1 min −1 and E L p = 101 kJ mol −1 for 35 °K/min. The deduced permeabilities fall within the range of values determined in a prior study by Levin (6). Analysis with the model also indicates that the turgor pressure exerts a negligible effect on yeast exposed to freezing stress.
Children as victims of parental conflict.

To the Editor.— The article by Nelson1 included particularly vivid examples of the manner in which children may become victims of parental conflict. In the experience of University of California Davis Medical Center9s Suspected Child Abuse and Neglect Team, similar cases (although less severe) account for approximately 2% of the physical abuse cases reviewed. Social services agencies tend to view such occurrences as "accidents," and are reticent to provide services to such families. Physicians must take an active role in advocating that the families and children receive appropriate services.
Analysis of Variance

The analysis of variance unites seemingly unrelated inferential methods into one exact procedure whose results can be reported in a single compact table. The analysis consists of partitioning the overall variability present in the data into parts reflecting the variability accounted for by explanatory factors and variability due to chance. If the amount of variability accounted for by an explanatory factor is enough larger than we would expect it to be simply due to the vagaries of random sampling, we conclude that there is a nonzero effect in the population due to the factor under examination. The analysis of variance allows a researcher to employ this logic while limiting the rate at which erroneous conclusions are drawn. Keywords: analysis of variance; test of means; F test; hypothesis testing
Supportive Care in Hematology

Patients with hematological malignancies such as leukemias and lymphomas are predisposed to a wide spectrum of infections that need special attention. These patients are immunosuppressed not only as a result of the immune defects associated with the underlying disease, but also because of the treatment regimens that generally further decrease the patient’s resistance to infections. An intensive transfusion support with platelets, red cell concentrates, immunoglobulins, cytokines, and other drugs is necessary. Many patients also need antiemetic agents, nutritional support, pain medication, and, very often, venous catheters. All of these measures are considered supportive care and apply in a similar fashion to the high-dose treatment of solid tumors. Supportive care measures, along with the treatment and prophylaxis of infections, are discussed in this chapter. Transfusion support is discussed in Chapter 22.
The capacity of conophthorin to enhance the attraction of two Xylosandrus species (Coleoptera: Curculionidae: Scolytinae) to ethanol and the efficacy of verbenone as a deterrent

Exotic invasive ambrosia beetles are among the most economically important pests of nursery stock and forest systems in the U.S.A. 2 Conophthorin, a common bark volatile of deciduous trees, acts as an attractant for the exotic black stem borer, Xylosandrus germanus (Coleoptera: Curculionidae: Scolytinae). Nevertheless, the extent to which a congener, Xylosandrus crassiusculus and other ambrosia beetles are attracted to conophthorin remains unclear. It is also unknown whether conophthorin enhances the attraction of these Xylosandrus beetles to traps baited with ethanol. 3 In the present study, we evaluated the extent to which conophthorin enhances the attraction of X. crassiusculus and X. germanus to ethanol-baited traps. We also tested the capacity of verbenone, an anti-aggregation pheromone component of several coniferophagous bark beetles, to deter both species. 4M oreX. crassiusculus were captured in traps baited with both conophthorin and ethanol than in those containing either compound alone, suggesting that conophthorin enhances the response of X. crassiusculus to ethanol. This combination was also attractive to the checkered beetles Madoniella dislocatus and Pyticeroides laticornis (Coleoptera: Cleridae). 5 Verbenone deterred both X. germanus and X. crassiusculus, suggesting that the use of conophthorin and ethanol as an attractant and verbenone as a deterrent can be incorporated into an effective integrated pest management programme.
k-space based regularization of a new pulse-echo image reconstruction operator

A novel regularization approach for reconstructive ultrasound pulse-echo imaging is introduced. This approach is based on weighted minimum-norm least-squares (WMNLS) solution derived from a discretized model of wave propagation in the region of interest (ROI). In previous work, regularization based on model rank reduction or single-parameter WMNLS were used. Even though they provided initial proof of concept, these approaches lacked physical intuition and often resulted in a artifacts in the point spread function (psf) that were hard to control. We introduce a new WMNLS that explicitly utilizes the k-space frequency components of the coded wavefront in the regularization process. The weighting matrix in the WMNLS is derived based on "desired" k-space representation of the imaging operator. This approach directly controls the lateral and axial frequency characteristics of the imaging operator and, therefore, the spatial and contrast resolution of the overall imaging system.
Prosodically-conditioned vowel shortening in Chindali

In Chindali [Bantu M21, northern Malawi and southern Tanzania], the augment vowel of noun classes 1 a, Sa, 9 and 10 exhibits allomorphic variation in length. In other noun classes, the vowel of the noun class prefix varies in length before NC initial stems. The author demonstrates that, in both cases, potentially long vowels become shortened, except that they do so under different conditions: mora-count of the noun stem in the first case, lack of high tone (accent) on the prefix in the second.
Involvement of the Prelimbic–Infralimbic Areas of the Rodent Prefrontal Cortex in Behavioral Flexibility for Place and Response Learning

The present experiments investigated the role of the prelimbic–infralimbic areas in behavioral flexibility using a place–response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic–infralimbic areas. To examine the role of the prelimbic–infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic–infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic–infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic–infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic–infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic–infralimbic areas are important for behavioral flexibility involving cross-modal but not intramodal shifts.
Soil Organic Carbon and Nitrogen Storage in Two Southern California Salt Marshes: The Role of Pre-Restoration Vegetation

Abstract Soil organic carbon and nitrogen storage represent important ecosystem services provided by salt marshes. To test the importance of vegetation on soil properties, we measured organic carbon, total nitrogen, and belowground biomass in two southern California salt marshes. In both marshes, cores were collected from areas which differed in dominant vegetation cover prior to the restoration of tidal influence. There were no differences in organic carbon or total nitrogen density between vegetation classes at either site; however, a relationship between belowground biomass and soil organic carbon suggests that vegetation may influence soil properties.
The advantage and disadvantage of Europeanism in Ernst Troeltsch: Its relationship to nationalism, Eurocentrism, and universalism

(1996). The advantage and disadvantage of Europeanism in Ernst Troeltsch: Its relationship to nationalism, Eurocentrism, and universalism. The European Legacy: Vol. 1, Fourth International Conference of the International Society for the study of European Ideas, pp. 720-726.
The rate of penetration of a fluid into a porous body initially devoid of adsorbed material (1, 2)

Abstract A generalization of the Washburn equation is given. It is shown that, if a porous body is initially devoid of any absorbed film of the liquid that penetrates it, and if the molecules of the fluid are not transported ahead of the liquid front at a rapid rate by diffusion, then the rate of penetration will be faster than that predicted by the Washburn equation. The maximum rate is given by d(x) 2 dt = K(γω cosθ Y +π e -π 0 ) γ where πe is the equilibrium spreading pressure and π0 is the spreading pressure at zero time, K is the tortuosity factor, γω the liquid surface tension, and θY the equilibrium contact angle. The actual rate will depend on the transport processes by which molecules can reach the film ahead of the liquid, and on the state of the adsorbed film. The conditions are discussed, under which the above equation will apply, and when the original Washburn equation will be valid.
Public perceptions of interpersonal violence

Abstract The United States is projected in both academic and popular literature as a nation with a high tolerance for violence and high incidence of violence. The study reported here measured community acceptance of crime and willingness to report acts of interpersonal violence to the police in 1986–1987 and 1991–1992. The results indicate that people have a relatively low level of acceptance of interpersonal violence and that this pattern is stable over time.
Stability and control of nuclear rocket propulsion

A systems treatment of the dynamic behavior of nuclear rocket propulsion systems is presented. This simplified analysis does represent the basic ideas of more detailed computer studies. Nuclear reactor systems for space propulsion are much faster than conventional reactor systems which complicates the controls problem. (The dynamics of chemical systems have been simpler in nature due to their speed of response.) One attractive solution, which uses the propellant reactivity, is discussed.
Effective Static Dissipation of Bilayer Thermoplastic Nanocomposites at Low Nanofiber Loadings

A bilayer-structured PEI/CNF composite fabricated by a facile solution casting method is described, showing dramatically improved static dissipation properties at a rather low loading level. Compared to the conventional monolayer nanocomposite with high static dissipation rate, the bilayer-structured composite exhibited a 91.4 wt.-% reduction in CNF loading, while it is volumetric and surface static dissipation rates were ca. 1000 and 20 times higher, respectively. The interface region in the bilayer structure accounts for such a remarkable improvement. It is believed that this design could significantly benefit the applications requiring high antistatic capability of polymeric materials.
Film and the digital in visual studies: film studies in the era of convergence

This article examines how the convergence of various media impacts upon the relations between film studies and visual studies. The questions raised are: How did visual studies emerge as a discipline with film studies in its purview? How does the digital, an aspect of late 20th-century visual culture which emerged roughly simultaneously with visual studies, figure into the field? What happens when film studies is embedded in or combined with visual studies? In acknowledging that visual studies is an outcome of and a response to the conditions of media convergence, this article ends by offering a sense of how questions around optical virtuality and medical imaging can make sense of the effects that media convergence is having on the conditions of experience and subjectivity within modernity.
Synthesis of tetrose nucleosides. I. Adenine nucleosides of erythrose and threose.

D- and L -Erythrose and D - and L -threose were individually converted to their triacetates which were condensed with chloromercuri-6-benzamidopurine in the presence of titanium tetrachloride. After deacylation, the four crude mixtures of anomeric nucleosides were each resolved on a strong anion exchange resin, leading to the isolation of all eight possible 9-tetrafuranosyladenines. The anomeric configurational assignments were made by consideration of the mechanism of nucleoside condensation (Baker's trans rule) and by Hudson's rules of isorotation. Preliminary results of tests for biological activity with Streptococcus faecalis 8043 and with adenosine deaminase are reported.
Antecedents and outcomes of contingent workers' attitudes toward their temporary help services firm: A unit level longitudinal investigation

This study explored the unit-level antecedents and outcomes of contingent workers' attitudes toward their temporary help services (THS) firm. It was proposed that (a) client-orientation levels of the THS firm's full-time staff would influence the level of support received by contingent workers, (b) staff supportiveness would be reciprocated by these workers in the form of favorable firm-directed attitudes, and (c) contingent workers' attitudes toward the THS firm would influence two unit-level outcomes—client reported service failure, and voluntary turnover rates of THS staff. Support was found for all the hypothesized relationships in a longitudinal study utilizing survey data gathered from 1324 full-time employees, 570 contingent workers, and 1951 clients; and archival data on staff turnover from 46 strategic business units (SBUs) of a THS firm. These results are discussed within the context of employee–organization relationship (EOR), contingent workforce, and service management literatures. Copyright © 2010 John Wiley & Sons, Ltd.
The E1 helicase of human papillomavirus type 11 binds to the origin of replication with low sequence specificity.

Expression of the human papillomavirus type 11 E1 and E2 genes is necessary and sufficient to support viral DNA replication. The full-length E2 protein is a transcriptional modulator that also interacts with the E1 helicase to form an E1/E2 complex at the viral origin of replication. Previous studies indicated that efficient binding of this complex to the replication origin is site-specific and that the E2 homodimer was required for efficient E1 binding. Human papillomavirus type 11 E2 and E1 proteins have been purified and their cooperative binding to the HPV type 11 viral replication origin has been characterized. Low-affinity E1 binding to the HPV type 11 replication origin was demonstrated and found to be largely nonspecific. DNA binding by E1 does not require complex formation with E2 and appears to be independent of ATP binding or hydrolysis. E1 binding quantitatively increased with the addition of increasing amounts of E2 and mutations in the E2 binding site demonstrated that the E2BS site is required for E1 and E2 to specifically bind as a high-affinity complex at the replication origin. Analysis of the A/T-rich E1 binding site via mutation showed that it was nonessential for high-affinity E1/E2 complex formation. Thus, although the replication functions between the animal and the human papillomaviruses are well conserved, there are subtle differences in the DNA binding requirements for E1, which may portend mechanistic differences among the DNA replication systems of various papillomavirus types.
Epistemology of Modeling and Simulation: Variations on a Theme

The three papers that follow formed part of a 3-day conference in the Epistemology of Modeling and Simulation at the University of Pittsburgh, 1st through 3rd April 2011 (www.modelingepistemology.pitt.edu). They reflect variations on a theme that emerged in the course of the conference both in more traditional paper sessions and in breakout workshops on specific computational models: the Long House Valley Anasazi model, the CCSM3 climate change model, and the Epstein smallpox model. The papers collected here concentrate on issues of modeling and simulation, experimentation, and materiality. Tarja Knuuttilla and Andrea Loettger’s “Modeling and Experimenting: The Combinatorial Modeling Strategy of Synthetic Biology” explores a triangulation strategy between model organisms, synthetic experimentation, and mathematical models and associated simulations. The authors argue that each of these fulfills a specific epistemic role, with an analysis of cases that adds significant nuance to older debates regarding simulation, experimentation, and materiality. The central modeling goal of simplification is the focus of Gerhard Konig’s “Simulation and the Problem of Simplification: Between Scylla and Charybdis?” Konig’s piece is particularly valuable in that it is not content to emphasize the dangers Philos. Technol. (2013) 26:73–74 DOI 10.1007/s13347-012-0080-9
Orthogonal decompositions for wavelets

Decompositions of Hilbert spaces in terms of reducing subspaces for wavelets operators, as well decompositions of these operators themselves, are investigated. In particular, it is shown on which reducing subspaces these operators act as bilateral shifts of multiplicity 1. We also exhibit the unitary transformation that performs the unitary equivalence between restrictions of them to appropriate reducing subspaces.
AC Electrokinetics for Biosensors

We develop here tools for speeding up binding in a biosensor device through augmenting diffusive transport, applicable to immunoassays as well as DNA hybridization, and to a variety of formats, from microfluidic to microarray. AC electric fields generate the fluid motion through the well documented but unexploited phenomenon, Electrothermal Flow, where the circulating flow redirects or stirs the fluid, providing more binding opportunities between suspended and wall-immobilized molecules. Numerical simulations predict a factor of up to 8 increase in binding rate for an immunoassay under reasonable conditions. Preliminary experiments show qualitatively higher binding after 15 minutes. In certain applications, dielectrophoretic capture of passing molecules, when combined with electrothermal flow, can increase local analyte concentration and further enhance binding.Copyright © 2004 by ASME
An Investigation of the Flow Physics of Vane Clocking Using Unsteady Flow Measurements

Vane clocking, the circumferential indexing of adjacent vane rows with similar vane counts, has been shown to affect stage efficiency in compressors and turbines. Steady flow measurements acquired in the embedded stage of the Purdue 3-Stage Compressor showed a change in stage efficiency with vane clocking, as discussed in a companion paper. The optimum efficiency condition at design loading occurred when the upstream vane wake impinged on the downstream vane, as had been reported by other vane clocking studies. However, at high loading, the impingement of the upstream vane wake triggered a vane suction side boundary layer separation and resulted in the worst efficiency condition. The objective of this research is to experimentally investigate the maximum and minimum efficiency clocking configurations with unsteady flow measurements to illuminate the flow physics associated with the measured changes in Stage 2 performance. Vane exit unsteady total pressure, velocity, and flow angle measurements were acquired at 50 pitchwise locations spanning one vane passage. Fourier decomposition is used to identify the impact of the upstream rotor wake on the shedding characteristics of the Stator 2 boundary layer and how the placement of the upstream vane wake affects this phenomenon. For the clocking configuration that located the Stator 1 wake at the leading edge of the Stator 2 vane at design loading, it dampened the boundary layer response to the fluctuating incidence associated with rotor wake chopping, leading to a reduction in the size of the structures shed in the Stator 2 vane wake. At the high loading condition, the placement of the Stator 1 wake at the leading edge of Stator 2 triggered a suction side boundary layer separation, resulting in an absence of the upstream rotor blade pass frequency in the spectrum measured in the Stator 2 wake.Copyright © 2008 by ASME
ECONOMICS AND GENERAL SYSTEMS

In my own recollections the Society for General Systems Research, as it later came to be called, originated in a conversation around the lunch table at the Center for Advanced Study in the Behavioral Sciences in Palo Alto, California, in the fall of 1954. The four men sitting around the table who became the founding fathers of the Society were Ludwig von Bertalanffy, Anatol Rapoport, Ralph Gerard, and myself—a biologist, an applied mathematician and philosopher, a physiologist, and an economist. Economics, therefore, can certainly claim to have been in at the beginning of that enterprise, although this may have been largely an accident of my own personal interests. Certainly one cannot claim that the interaction between general systems and economics has been very extensive since that date, though the contributions of each to the other may be more than many people recognize. In the intervening years, however, the social sciences in general systems have been represented more by sociologists, such as Buckley,1 and psychologists, such as the late Kenneth Berrien.2 Almost the only other economist I can think of who has played much of a role in the development of general systems is Alfred Kuhn,3 whose interest, like my own, has been primarily in going beyond economics to developing an integrated social science.
The preoperative assessment clinic: organization and goals

Abstract The current challenge of preoperative evaluation is to perform value based, efficient and effective preoperative assessments which result in maximum operating room efficiency. In an era of diminishing health care resources, efficient organization and utilization of those resources available in the preoperative clinic will result in cost savings via reductions in operating room delays and cancellations. Effective organization can also reduce laboratory testing and the use of outside consultation. Fostering a patient-centered focus in the preoperative clinic can reap the additional benefits of increased patient satisfaction and confidence in the hospital and health care providers.
Heartbeat rate modulation mediated by the ventral nerve cord in the honey bee, Apis mellifera

Using impedance conversion as a recording technique, heartbeat patterns were established for intact adult honey bee workers during rest and during nectar feeding and locomotion, activities that both result in accelerating heartbeat. Heartbeat patterns were then described separately for bees in which assumed neural regulation was disrupted (the ventral nerve cord was transected), and for bees in which assumed neurohormonal regulation was disrupted (blood circulation to the abdomen was blocked). Heartbeat patterns from these latter two groups were compared with the baseline data from the former three groups. Results showed that normal modulatory patterns occurring during feeding and locomotion persisted when the neurohormonal pathway was disrupted, but the same modulation was absent when the neural pathway was disrupted. These results offer clear support for the conclusion that neural mechanisms provide a primary form of regulation of heartbeat in the honey bee.
Oxohexestrol derivatives labeled with fluorine-18. Synthesis, receptor binding and in vivo distribution of two non-steroidal estrogens as potential breast tumor imaging agents

Abstract We have prepared two non-steroidal estrogens in the 2-oxohexestrol series labeled with the positron-emitting radionuclide fluorine-18, 1-fluoro-5-oxohexestrol (4) and 1-fluoro-2-oxohexestrol (5). We anticipated that the polar ketone function at the interior of these ligands would reduce their level of non-specific binding, which might increase the selectivity of their uptake in vivo. The two compounds were prepared by total synthesis: compound 4 was prepared in fluorine-18 labeled form by [18F]fluorine ion displacement on a suitably protected methanesulfonate precursor followed by deprotection under acidic hydrogenolytic conditions; the isomer 5 was prepared from a protected α-keto trifluoromethanesulfonate precursor with deprotection under basic conditions as the final step. The binding affinity of these hexestrol derivatives for the estrogen receptor was determined by competitive radiometric binding assays at 0 and 25 °C, and their lipophilicity (as octanol-water partition coefficients, log P values) and non-specific binding were estimated. The log P values determined by a reversed phase HPLC method were higher, relative to estradiol, than those calculated by the fragment method of Rekker. In tissue distribution studies in immature (50 g) rats, both of these compounds showed selective uptake in estrogen target tissues. At 1 h, activity in the uterus reached the level of 2.5–3.0% of the injected dose per gram tissue, with uterus-to-blood and uterus-to-muscle ratios of 14–20 and 8–14, respectively. The uptake efficiency and selectivity of these fluoro-oxohexestrols in principal estrogen target tissues is less than that of fluorine-18 labeled steroidal estrogens we have prepared previously, but their receptor-mediated uptake in certain secondary target tissues is substantial. The specific and non-specific components of target tissue uptake of these two compounds appear to be directly related to their non-specific binding and their binding selectivity.
Preferential but Not Exclusive T Cell Receptor Vβ Chain Utilization of Myelin Basic Protein and Peptide-Specific T Cell Clones in Mice

Abstract The repertoire of T cell receptor (TCR) Vβ chain utilization was investigated in PL/J, CXJ-1, SJL/J and B10.S → SJL/J chimeric mice in response to either myelin basic protein (MBP) or the strain-specific encephalitogenic peptide. Our analysis showed that there was an overlapping predominance in the TCR Vβ gene utilization in the MBP-specific responses, which were independent of the major histocompatibility complex (MHC) class II haplotype present, and the immunodominant peptide region recognized in these different strains. In those mice having the TCR Vβ b haplotype (PL/J, CXJ-1, and the B10.S → SJL chimera) either the TCR Vβ 4, 8, and 13 or the TCR Vβ 4, 6, and 13 predominated. In contrast, in mice with TCR Vβ a haplotype (SJL/J) Vβ 4, 6, and 17a were found. However, the quantitative distribution of these preferentially utilized TCR Vβ chains in each strain was defined by the MHC class II haplotype and the immunodominant peptide recognized. The expression of the Vβ8 gene product in the peripheral TCR repertoire did not always correlate with predominant Vβ8 utilization in the MBP-specific response.
Use of antipsychotics and psychostimulants for challenging behaviors in the intellectually disabled

Challenging behavior is a term often used in the field of the intellectually disabled (ID) to define a range of disruptive and dangerous actions. Behaviors often referenced in this category include aggression, hyperactivity, impulsivity, self-injury, property destruction, and occasionally obsessive-compulsive behaviors. These behaviors not only burden the individual but also increase strain on caregivers and impair social interactions. The incidence of disruptive behaviors and/or self-injury has been cited as occurring in 10-62% of individuals with ID, regardless of age, residing in institutions as well as in community settings. For children and adolescents with ID, the reported rate of impulsivity and aggression is about 20%. It should be noted both impulsivity and aggression often manifests earlier in individuals with ID than typically developing individuals. Psychotropics are used more frequently in the institutional settings, and adults are often prescribed psychotropic medications more often and at higher doses. Because of the persistent and prevalent nature of challenging behaviors, polypharmacy often becomes a factor during treatment; however, behavioral therapies should not be ignored. Due to longer periods of treatment, higher doses, and polypharmacy, individuals with ID may be predisposed to be the most overmedicated patient population.
A new estimate of volatile outgassing on Mars

The presence of 28% argon on Mars, as calculated by Levine and Riegler (1974) and indirectly inferred from Soviet Mars-6 lander data, has important implications for the outgassing history of H2O, CO2, and N2 on Mars. Even if the terrestrial volatile outgassing ratio is only approximately valid for Mars, then large quantities of H2O (of the order of 100,000 g/sq cm), about 10,000 g/sq cm of CO2 (about 1000 times more CO2 than found at present in the Martian atmosphere), and some 450 g/sq cm of N2 may have outgassed over the history of Mars.
Development of a novel clinical biomarker assay to detect and quantify aggrecanase-generated aggrecan fragments in human synovial fluid, serum and urine

Summary Objective Proteolytic degradation of aggrecan in articular cartilage is a hallmark feature of osteoarthritis (OA). The present study was aimed at developing a sensitive enzyme linked immunosorbent assay (ELISA) for the detection of aggrecanase-cleaved fragments of aggrecan in human serum and urine to facilitate the clinical development of aggrecanase inhibitors for OA. Methods The BC3 monoclonal antibody that detects the ARGS neoepitope sequence in aggrecanase-cleaved aggrecan was engineered and optimized using complementarity determining region (CDR)-saturation mutagenesis to improve its binding affinity to the neoepitope. A sandwich ELISA (BC3-C2 ELISA) was developed using the optimized α-ARGS antibody (BC3-C2) as capture antibody and a commercially available antibody directed against the hyaluronic-acid binding region (HABR) of aggrecan as detection antibody. Aggrecanase-cleaved fragments of aggrecan present in in vitro digests, human cartilage explant culture supernatants and in human synovial fluid, serum and urine were detected and quantified using this ELISA. Results The optimized antibody had a 4-log improvement in affinity for the ARGS containing peptide compared to the parental BC3 antibody, while maintaining the ability to not cross-react with a spanning peptide. The BC3-C2 ELISA demonstrated the ability to detect aggrecanase-cleaved aggrecan fragments in the native state, without the need for deglycosylation. This ELISA was able to measure aggrecanase-generated ARGS containing aggrecan fragments in human articular cartilage (HAC) explant cultures in the basal state (without cytokine stimulation). Treatment with an aggrecanase inhibitor resulted in a dose-dependent inhibition of ARGS neoepitope released into the culture supernatant. The ELISA assay also enabled the detection of ARGS containing fragments in human synovial fluid, serum and urine, suggesting its potential utility as a biomarker of aggrecanase activity. Conclusions We have developed a novel ELISA using an optimized ARGS antibody and have demonstrated for the first time, an ELISA-based measurement of aggrecan degradation products in human serum and urine. This assay has the potential to serve as a mechanistic drug activity biomarker in the clinic and is expected to significantly impact/accelerate the clinical development of aggrecanase inhibitors and other disease modifying drugs for OA.
Preface to the special issue

Why are there fewer women in careers related to math, science, and technology? Why does this phenomenon appear robust across a number of countries? Why, despite a concentration of research into this question over the last 25 years, and numerous policy documents and educational efforts, do we still see gendered representation in these careers in the 21st century? Although women have been making gains in entering traditionally male-dominated professions, and in entering the workforce in general, gender differences persist. Females are both less likely to choose careers in those fields, and also to leave them if they do enter them (American Association of University Women, 1993; National Center for Education Statistics, 1997; National Science Foundation, 1999). A resurgence of interest into the question has been prompted in part by a general shortage of people entering so-called ‘‘STEM’’ careers (in Science, Technology, Engineering, and Math). At the same time, researchers concerned with gender equity have continued to question the reasons for women’s lower representation in STEM. Ever since Lucy Sells voiced social concerns about lower female participation in math courses in her identification of math as the ‘‘critical filter’’ limiting access to many high-status high-income careers (Sells, 1980), others have also argued that many females prematurely restrict their educational and career options by discontinuing their mathematical training in high school or soon after (Bridgeman & Wendler, 1991; Heller & Parsons, 1981; Lips, 1992; Meece, Wigfield, & Eccles, 1990). A major impetus for our Special Issue was to draw together researchers who are each utilizing multi-wave longitudinal data to address this central issue from a variety of perspectives. A unique feature of this Special Issue is our inclusion of studies that represent multiple waves of longitudinal data. Rather than speculating about how processes may unfold over time to produce certain outcomes, longitudinal studies allow us to draw strong conclusions regarding those processes, and to tease apart and test out a range of theoretical models. Empirical bases are large-scale longitudinal
Etiology of valvular heart disease

The incidence of congenital valvular heart disease has not significantly altered in recent decades. Major factors contributing to altered profiles of acquired valvular heart disease in the past few decades include an increased elderly segment of the population and increasing recognition of nonrheumatic forms of valvular heart disease. Mitral valve prolapse, and similar involvement of other valves, together with senile calcific aortic stenosis have emerged as the most common forms of valvular heart disease in developed countries. Body leanness and hypertension are additional etiological factors for senile calcific aortic stenosis. Severe calcification of a congenital bicuspid aortic valve continues to be an important cause of aortic stenosis in the elderly. Idiopathic degeneration of the aortic and mitral valves, apparently a different condition than mitral valve prolapse, has also become recognized. Despite a recent increase in the incidence of acute rheumatic fever in North America, rheumatic heart disease remains an infrequent cause of valvular heart disease in developed nations. Its incidence has diminished in the Middle East, but it is still frequent in underdeveloped countries. Intravenous drug abuse is increasing in importance as a cause of valvular heart disease in urban centers in the United States. Syphilitic heart disease is very rare.
Analysis of a Repeat‐Containing Family of Giardia lamblia Variant‐Specific Surface Protein Genes: Diversity Through Gene Duplication and Divergence

Giardia lamblia trophozoites express on their surfaces one of a set of cysteine-rich antigenically variant proteins, called variant-specific surface proteins, which comprise the majority of proteins detected by surface labeling. While these VSP proteins may be immunodominant proteins important in the host immune response to G. lamblia, the ability to switch expression from one VSP to another may provide a means for the trophozoites to avoid the host immune response. The first VSP characterized, VSPA6 (from the A6 clone of the WB isolate, originally termed CRP170), contains 18-23 copies of a 65 amino acid repeat. We have now used the repeat as a probe to isolate from a WBA6 genomic library two genes related to vspA6 (called vspA6-S1, vspA6-S2). Sequence analysis of the vspA6-S1 gene revealed nearly two complete copies of the 195 bp repeat and substantial nucleotide and translated amino acid similarity in the coding regions 5' and 3' to the repeats. The vspA6-S2 gene, while still related, showed greater divergence from vspA6 than vspA6-S1 in the nonrepeat coding region and contained nearly four copies of a 201 bp repeat that was 75% identical to the 195 bp vspA6 repeat. These results suggest that gene duplication followed by divergence has played a key role in the generation of the vsp gene repertoire.
Geographic variation in the diet of hypsodont herbivores from the Rancholabrean of Florida

Classifying the diet of ancient animals is important for understanding biological phenomena such as resource partitioning and the evolution of particular environments. Focusing on Bison, Equus, and Mammuthus from three geographical areas of Florida (north, central, and south) during the Rancholabrean, this study uses values of stable carbon isotope composition of tooth enamel carbonate collected from the literature to determine dietary variability, and whether hypsodonty and comparisons with modern analogs accurately represent the scope of forage taxa could utilize. Carbon isotope values show no significant differences in diet between Bison, Equus, and Mammuthus within any of the three designated geographic areas of Florida. The data do show significant differences in diet for Bison between north Florida and south Florida, for Equus between north Florida and south Florida and between central Florida and south Florida, and for Mammuthus between central Florida and south Florida. These results suggest floral differences among the geographic areas of Florida. Mean d 13 C values for the taxa suggest that each was an intermediate feeder with a strong preference for grasses and sedges. Comparisons of diet in this study with those based on modern analogs and hypsodonty indicate that both techniques may accurately represent a taxon’s average diet. However, the range in d 13 C values observed in individuals extended from strict C4 feeding to strict C3 feeding and suggests a range in diet from grazing to browsing. This wide range in apparent diet indicates that multiple specimens are required to accurately interpret the feeding strategy of taxa and the relevance of the diet of animals as an indicator of environment in which they lived. D 2004 Elsevier B.V. All rights reserved.
The plasma-cathode electron gun

The plasma-cathode electron gun, which is being developed for operation with pulsed and cw e-beam lasers, is described. This device employs a plasma generated within a low-voltage hollow-cathode discharge as the source of electrons (1). Electrons extracted from the plasma pass through a triode-type control grid structure and are accelerated to high energies in a plasma-free region prior to emerging from the gun through a thin foil window. Experimental results obtained with 4×40 cm and 5×125 cm e-guns will be described. These devices have operated under cw conditions at beam energies in excess of 150 keV and beam current densities of 0.1 mA/cm2; earlier experiments have demonstrated the capability for cw and pulsed current densities up to 1 mA/cm2 and 100 mA/cm2, respectively. The plasma cathode electron gun offers an attractive alternative to other e-gun designs for many applications.
Differential distribution of inositol 1,4,5-triphosphate receptors in the rat olfactory bulb.

The inositol 1,4,5-triphosphate receptor (IP3R) regulates the release of calcium from intracellular stores. In the present study, the distribution of IP3R in the rat main olfactory bulb was determined by immunohistochemistry. Immunofluorescence was used to double label for IP3R and for g-aminobutyric acid (GABA) or for projection neurons, which were retrogradely labeled following dextran injection into the lateral olfactory tract (LOT). The expression profile of IP3R changes dramatically during development. In the glomerular layer of adults, many juxtaglomerular neurons are IP3R immunoreactive [IP3R(1)]; the majority of these cells are also GABA immunoreactive [GABA(1)]. Scattered sparsely throughout the external plexiform layer are small numbers of IP3R(1) neurons, a small number of which are LOT-projecting tufted cells. Significant numbers of IP3R(1) neurons are in the granule cell layer; however, most of these cells are GABA(2). The vast majority of mitral cells contain little or no IP3R immunoreactivity. These findings indicate that, in the olfactory bulb of adult rats, IP3R is preferentially localized in specific classes of intrinsic neurons and that it is rarely expressed in projection neurons. In contrast, during the first postnatal week, the receptor is detected almost exclusively in mitral cells. Expression of IP3R in subclasses of intrinsic neurons begins during the second and third weeks, concomitant with a decrease in immunostaining of mitral cells. Adult patterns of IP3R immunostaining are apparent by the fourth postnatal week. These observations raise the possibility that the expression of IP3 Ri n specific classes of neurons during development is activity dependent. J. Comp. Neurol. 389:224‐234, 1997. r 1997 Wiley-Liss, Inc. Indexing terms: IP3R; intracellular calcium stores; signal transduction; mitral cells; glomerulus
Ecosystem modeling of waterhyacinth management in Lake Alice, Florida☆

Abstract A mathematical model was developed for Lake Alice, a small, eutrophic, Kars-topography lake in Gainesville, Florida. The management of the floating aquatic plant, the waterhyacinth ( Eichhornia crassipes ) was considered one of the main objectives of the model. Simulated diversion of the treated sewage inflow reduced waterhyacinths by 50% or more. Dissolved oxygen remained low. Simulated diversion of the diluting effect of a heating plant effluent led to complete hyacinth takeover and much greater seasonal oscillations in the chemical parameters. Simulated hyacinth control caused the greatest dissolved oxygen fluctuations when spraying and periodic harvesting were tested and least with continuous harvesting. It was suggested that the above mentioned diversions were shown to be ecologically unattractive even without considering the economic costs of alternatives to lake disposal.