cssi/SciSciGPT-SciSciNet huggingface dataset:
Serum harvested from heifers one month post-zeranol implantation stimulates MCF-7 breast cancer cell growth

Breast cancer is a serious disease in the US. Numerous risk factors have been linked to this disease. The safety of using growth promoters, such as zeranol, remains under debate due to the lack of sufficient in vitro and in vivo evidence. Using CellTiter 96(™) Aqueous Non-Radioactive Cell Proliferation assay, real-time PCR and Western blot analysis, we evaluated the effects of sera harvested from experimental and control heifers before and after one month of zeranol implantation on the growth of human breast cancer cell line MCF-7 as well as the involved mechanisms. We found that sera harvested from the heifers following one month of zeranol implantation were more mitogenically potent in stimulating the proliferation of MCF-7 cells when compared to sera harvested from the same heifers before zeranol implantation and the control heifers. Further investigation found that dextran-coated charcoal suppressed the stimulating effect of the sera on MCF-7 cell growth. The mechanisms involved in the MCF-7 cell proliferation stimulated by zeranol-containing sera may include up-regulation of cyclin D1 and down-regulation of p53 and p21 expression at the mRNA and protein levels in the cells. The results suggest that the consumption of beef products containing biologically active residues of zeranol or its metabolites is a risk linked to breast cancer development. Further investigation is required in order to clarify this critical issue.
In vitro antitumor activity of 9-nitro-camptothecin as a single agent and in combination with other antitumor drugs.

Preclinical studies at Roswell Park Cancer Institute by Minderman, Cao, and Rustum (unpublished results) showed that a combination of SN-38 and 5-FU against HCT-8 human colon carcinoma cells in vitro was synergistic, with the best interaction occurring when the drugs were added sequentially, SN-38 first. Their in vivo studies using HCT-8 tumor xenografts implanted s.c. in nude athymic mice demonstrated superior efficacy for a sequential i.v. administration of CPT-11, 24 hr before 5-FU. On the basis of these studies, our group has begun to evaluate effects of RFS2000 (9-nitro-20(S)-camptothecin) (9-NC) in combination with a series of other antitumor agents. Using a panel of human tumor cell lines including A121 ovarian cancer, HCT-8 colon cancer, H-460 NSCLC, HT-1080 fibrosarcoma, and MCF7 mammary cancer, we found that a 2-hr exposure to 9-NC resulted in ID50 values of < 1.0 microM, whereas continuous exposure to drug resulted in ID50 values of < 1.0 nM. Tumor growth inhibitory activities of 5-FU, gemcitabine, and paclitaxel were determined for comparison. Combinations of these agents were evaluated with 9-NC using the human HCT-8 colon tumor cell line. Concurrent and sequential combinations of 9-NC with 5-FU had some regions of the concentration-effect surface with local synergy and some with local antagonism. However, sequential combination of 9NC or SN-38 followed by 5-FU, 24 hr later appeared to be highly synergistic at high dose-effect levels (i.e., ID90), suggesting that sequential drug administration may be more efficacious at high effect level and that the order of drug addition is very important. Overall, our results were similar to that found earlier by Rustum's group with CPT11 (or SN-38) and 5-FU, suggesting that sequential combination of 9-NC (or other camptothecin analogues) followed by 5-FU has potential for the treatment of cancer in man.
High-Frequency Oscillations Are Not Necessary for Simple Olfactory Discriminations in Young Rats

Individual olfactory bulb mitral/tufted cells respond preferentially to groups of molecularly similar odorants. Bulbar interneurons such as periglomerular and granule cells are thought to influence mitral/tufted odorant receptive fields through mechanisms such as lateral inhibition. The mitralgranule cell circuit is also important in the generation of the odor-evoked fast oscillations seen in the olfactory bulb local field potentials and hypothesized to be an important indicator of odor quality coding. Infant rats, however, lack a majority of these inhibitory interneurons until the second week of life. It is unclear if these developmental differences affect olfactory bulb odor coding or behavioral odor discrimination. The following experiments are aimed at better understanding odor coding and behavioral odor discrimination in the developing olfactory system. Single-unit recordings from mitral/tufted cells and local field-potential recordings from both the olfactory bulb and anterior piriform cortex were performed in freely breathing urethane-anesthetized rats (postnatal day 7 to adult). Age-dependent behavioral odor discrimination to a homologous series of ethyl esters was also examined using a cross-habituation paradigm. Odorants were equated in all experiments for concentration (150 ppm) using a flow dilution olfactometer. In concordance with the reduced interneuron population, local field potentials in neonates lacked detectable odor-evoked γ-frequency oscillations that were observed in mature animals. However, mitral/tufted cell odorant receptive fields and behavioral odor discrimination did not significantly change, despite known substantial changes in local circuitry and neuronal populations, over the age range examined. The results suggest that high-frequency local field-potential oscillations do not reflect processes critical for simple odor discrimination.
Multi-state component importance analysis using multi-state multi-valued decision diagrams

Component importance analysis helps identify the vulnerabilities within a system and quantify the criticality of the system components. Multi-state component importance analysis poses unique challenges to the existing methods that are primarily based on binary-state applications. This paper presents a multi-state multi-valued decision diagram-based analytical method for multi-state component importance analysis. The advantages of the proposed method are illustrated through the comparison to a Monte Carlo simulation-based method and the detailed analysis of a case study.
FireCracker: A Framework for Inferring Firewall Policies using Smart Probing

A firewall policy that is correct and complete is crucial to the safety of a computer network. An adversary will benefit a lot from knowing the policy or its semantics. In this paper, we propose a framework that could be used to blindly discover a firewall policy remotely as a black box and without prior knowledge about the network configuration. We show how an attacker can reconstruct a firewall's policy by probing the firewall with tailored packets into a network and forming an idea of what the policy looks like. The proposed methodology shows how to discover a policy that is semantically equivalent to the original one used in the deployed firewall. Three techniques are proposed for reconstructing the policy as well as to intelligently choose the probing packets adaptively based on the firewall response. We show the possibility of obtaining the deployed policy in a feasible time with acceptable accuracy.
CXXV. A restricted quantum statistical proof of the third law of thermodynamics

Abstract A restricted proof is given of the third law of thermodynamics. The restriction resides in the fact that the proof applies only in the limit of an infinitely large system (the ‘limit L ’). An additional restriction is that it applies only to non-interacting and structureless quantum mechanical particles whose quantum states satisfy certain requirements (the ‘class 0’ of systems). The essence of the proof depends on showing that the free energy of the system, as averaged over a grand canonical ensemble and expressed per unit volume of the system, is of the form a-bTd (b>0) near the absolute zero.
Amino -derivatives of the sesquiterpene lactone class of natural products as prodrugs

The sesquiterpene lactone class of natural products displays a diverse array of biological activities due to the presence of the α-methylene-γ-lactone motif. However, clinical translation of this class has been hampered by poor aqueous solubility and non-selective binding as a Michael acceptor at undesired targets. A prodrug approach has been developed to overcome these problems in which an amine is added into the α-methylene-γ-lactone to mask this group from nucleophiles and increase solubility. The medicinal chemistry of amino-derivatives of the sesquiterpene lactones is described, beginning with synthetic development, moving into pharmacological applications, and finishing with clinical translation.
Effect of Design and Kinetic Parameters on the Control of Cooled Tubular Reactor Systems

The steady-state design of cooled tubular reactor systems involves tradeoffs between reactor costs and compression costs, which are both affected by kinetic parameters and by tube geometry (diameter, length, and number). Peak temperatures occur in cooled reactors, which makes temperature control more challenging and which might necessitate the use of multiple temperature measurements along the length of the reactor. This paper considers the impact of these parameters on the dynamic controllability of the system. The exothermic, irreversible, gas-phase reaction A + B → C occurs inside the tubes of a packed tubular reactor. Steam is generated on the shell side to remove heat. The process consists of a feed−effluent heat exchanger, furnace, reactor, partial condenser, separator, and recycle compressor. Cases are explored that have different kinetic parameters (specific reaction rates and activation energies), different design parameters (tube diameters and reactant concentrations), and different control stru...
Dipole moments, property contribution tensors and effective conductivity of anisotropic particulate composites

The paper addresses the homogenization problem for a particulate composite with anisotropic constituents. Its specific goal is to bridge the gap between two different approaches to the problem of homogenization focusing on the anisotropic materials and to identify and discuss the key microstructural parameters affecting overall conductivity of heterogeneous materials. The basic concepts of the homogenization theory including a consistent way of introducing the macroscopic field parameters are discussed and clarified. The exact explicit relations have been obtained between the dipole moments, property contribution tensors and effective conductivity of composite with phase anisotropy of the general type. A detailed comparison of the analytical expressions for the dipole moments obtained by the multipole expansion method and the independently derived expressions for the conductivity contribution tensors has been made between and their equivalence is shown for the matrix type composites with transversely isotropic constituents and spheroidal inhomogeneities. The numerical examples illustrate effect on the overall conductivity of particulate composite of the properties of constituents, shape, volume content, spatial arrangement and orientation of particles.
Liquid Filters for UV Resonance Raman Spectroscopy

Solutions of organic compounds are proposed as viable high-pass, Rayleigh rejection filters for ultraviolet resonance Raman spectroscopy. The steep transmittance curves of these solutions effectively reject elastically scattered light in this region while passing Raman-shifted frequencies. The materials used in the filters are readily available and inexpensive, and the solutions are easily prepared. Filters for four lines in the range of 288 nm to 342 nm from a Raman-shifted 3rd and 4th harmonic of a Nd:YAG laser are presented, although the principle of preparing similar liquid filters can be applied to virtually any near-UV wavelength. The use of these filter solutions in conjunction with a single monochromator was found to significantly reduce levels of elastically scattered light without sacrifice of optical throughput; Raman scattering at frequency shifts within 200 cm-1 of the Rayleigh line could be observed, and the transmittance at shifts >1000 cm-1 was ≥80%. The Rayleigh-line rejection efficiencies for the filters in this study are modest (102-103) compared with those for filters employed in the visible region; but they can be easily boosted by increasing the chromophore concentration or filter pathlength with a trade-off of throughput for Raman scattering at small wavenumber shifts.
Attitudes Toward Counseling and Alternative Support Among Muslims in Toledo, Ohio

This descriptive cross-sectional study is designed to describe subgroup variation in attitudes toward help-seeking, and to determine perceived need for and actual use of professional counseling among Muslims in Toledo, Ohio. The study hypothesized that there are meaningful and statistical relationships between socio-demographic variables and attitudes, perceived need and reported use and that there will be differences in these relationships between African American, Arab, and South Asian Muslims. 459 Muslims (44 African Americans, 240 Arabs, 119 South Asians and 56 Others) participated in the study. Participants completed self-report questionnaires including a demographic data sheet and a shortened form of Fischer and Turner's Attitudes Toward Seeking Professional Psychological Help Scale (Fischer and Farina, 1995). Analysis indicated that age and sex were significantly associated with attitudes toward help-seeking. Sex was also associated with the need for counseling. Age, attitude and need for counselin...
The Human Amygdala and the Induction and Experience of Fear

Although clinical observations suggest that humans with amygdala damage have abnormal fear reactions and a reduced experience of fear, these impressions have not been systematically investigated. To address this gap, we conducted a new study in a rare human patient, SM, who has focal bilateral amygdala lesions. To provoke fear in SM, we exposed her to live snakes and spiders, took her on a tour of a haunted house, and showed her emotionally evocative films. On no occasion did SM exhibit fear, and she never endorsed feeling more than minimal levels of fear. Likewise, across a large battery of self-report questionnaires, 3 months of real-life experience sampling, and a life history replete with traumatic events, SM repeatedly demonstrated an absence of overt fear manifestations and an overall impoverished experience of fear. Despite her lack of fear, SM is able to exhibit other basic emotions and experience the respective feelings. The findings support the conclusion that the human amygdala plays a pivotal role in triggering a state of fear and that the absence of such a state precludes the experience of fear itself.
Drinking in violent and nonviolent events leading to arrest: Evidence from a survey of arrestees

The minimal requirements for evaluating the relative magnitude of acute and chronic effects of alcohol on violent crimes include: (a) a selection of comparable samples of violent and nonviolent events, and (b) adequate controls for the anticipated positive correlation between drinkers and drinking in feasible samples. Following these requirements, hypotheses about the impact of personal drinking patterns and drinking in events on violent crimes in a random sample of 1,147 arrestees interviewed in a California detection facility in 1989 were tested. Using multiple indicators of drinking in events, and taking into account errors of misclassification and correlations between drinkers and drinking, it was found that arrestees charged with violent crimes showed significantly higher rates of drinking in events related to arrest. On the other hand, the twelve-month drinking pattern of arrestees did not discriminate between violent and nonviolent charges in this sample, given controls for drinking in events.
AGU Career Center attracts hundreds of Fall Meeting attendees

The poster hall of the 2011 AGU Fall Meeting was the venue not only for scientific discussion and exchange of ideas—Fall Meeting attendees also explored new career opportunities and received career advice at AGU's Career Center. For many years, recruiters and hiring managers have found ideal candidates for open positions during the AGU Fall Meeting through the Career Center. Last year was no exception: Recruiters browsed resumes, visited posters, and attended talks to find talented individuals to interview during the week. In addition, hundreds of meeting attendees looking for a new job or a postdoc position visited the Career Center and checked the online AGU Career Center job board to request interviews. Career counselor Alaina Levine of Quantum Success Solutions gave private one-on-one career advice to 47 meeting attendees, making sure that each individual she counseled left the session with clearer career objectives and tactics to bring these objectives to fruition.
DYANA: dynamics analyzer-programmer: part I: description and application

The procedure for writing down the equations of motion of certain classes of dynamic systems is explicit, particularly those to which Kirchoff's laws and/or D'Alembert's principle can be applied. The Dynamics Analyzer-Programmer (DYANA) is a program developed for the International Business Machines Corporation (IBM) 704 EDPM which utilizes such a procedure, and from a physical description of a system develops a mathematical model and a resulting program. The objectives in setting up DYANA were:1. To permit an easy description of dynamic systems to a computer.2. To provide an automatic analysis by a computer to establish the mathematical model of the behavior of the system.3. To prepare a complete computer program to numerically solve the mathematical model.
Molecular shuttles: directed motion of microtubules along nanoscale kinesin tracks

Nature has evolved specialized molecules, motor proteins, to actively transport molecules over long distances. Such molecule-based energy dependent transport processes would be useful in nanotechnology or material sciences, for example to facilitate local assembly or repair processes, or to mediate rapid transport of nonbiological molecules. In an effort to elucidate how to control the movement of biological motors in synthetic environments, we use highly oriented poly(tetrafluoroethylene) films functionalized with the motor protein kinesin and find that they are able to direct the motion of microtubules in straight lines along the films' orientation axes. Potential mechanisms by which guidance occurs are discussed.
FR-4 and CMOS: Enabling Technologies for Consumer Volume Millimeterwave Applications

The past few years has witnessed the emergence of CMOS based circuits operating at millimeter wave frequencies. Integrated on a low cost organic packaging, this is the promise for high volume fabrication, lowering the cost and opening huge commercial markets. As standardization efforts catalyzed the interest and investment of industry and agencies, one can be assured of ubiquitous millimeter-wave technology in the consumer electronic market place in the fairly near future.
Endoscopy: Gastrointestinal endoscopy reporting: time for standardization?

With the increased emphasis on quality and standardization in gastrointestinal endoscopy, a need exists for minimum standardized information to be provided in endoscopy reports. A group of international colleagues provide a consensus document of standardized endoscopy reporting, including nomenclature and imaging, which is an important framework for all endoscopists, especially trainees.
Ultrahigh Vacuum Chemical Vapor Deposition of Doped and Intrinsic Si1 − x C x Epitaxy from Disilane, Trimethylsilane, and Phosphine

Epitaxial Si 1―x C x alloys grown in recessed source/drain junctions of n-channel MOSFETs are of interest to induce uniaxial tensile strain in the channel for electron mobility enhancement. In this work, we have studied chemical vapor deposition of intrinsic and heavily phosphorus-doped Si 1―x C x epitaxial layers on silicon using disilane, trimethylsilane, phosphine, and hydrogen as the gaseous precursors. The results show that phosphorus segregation to the growth surface can be fully suppressed by growing the layers at or below 550°C. The best films were obtained at this temperature yielding a growth rate of 4 nm/min. A maximum phosphorus concentration of 1.3 × 10 21 cm ―3 was obtained with a minimum resistivity of 0.67 mΩ cm and a substitutional carbon concentration of 1.0%.
26 PSYCHOSOCIAL ADJUSTMENT OF ADOLESCENT SEXUAL ABUSE VICTIMS

To assess adolescent psychosocial adjustment, 20 female sexual abuse victims completed the Offer Self-Image Questionnaire (OSIQ). The mean age of the victims was 12.9 years (9-15). Alleged assault was intrafamilial in 13 cases lasting several months to 10 years in 7 instances, of unknown length in 5, and was an isolated event in 1 case. All extrafamilial abuse were isolated events, committed by strangers in 5 cases and acquaintances in 2. Intercourse was alleged in 18 of the 20 cases. Results of the OSIQ demonstrated group mean scores in the poorly adjusted range for 3 scales indicating serious problems with sexual attitudes, family relationships and feelings of inability to master the external environment. While the group mean score for the Overall Adjustment Scale was within normal limits, 10 of the 20 girls had scores in the range indicating severe problems in adjustment; 7 of these 10 poorly adjusted individuals were incest victims. When mean sexual abuse OSIQ scores were compared to mean OSIQ scores for adolescent patients from a general adolescent medicine clinic, a significant difference was found only on the Sexual Attitude Scale (p<.05). While adolescent sexual abuse victims experience and report many problems and distressing conflicts that warrant intervention, we can find no evidence to support the previous contention that these victims are uniformally seriously psychologically disturbed or represent a deviant population.
Three-dimensional audio localization using wavelet-domain convolution

This paper describes a new approach for creating compelling virtual acoustic environments by synthesizing and three-dimensionally localizing sounds within the wavelet-domain. A prototype system was developed that combines wavelet-domain convolution for localization with Miner's new method for synthesizing parametrically controlled sounds. Results are presented and discussed, with suggestions as to directions of further interest.
Biliary atresia begins before birth

Although the specific etiology of biliary atresia (BA) is unknown, evidence is accumulating that this disease is a dynamic process that begins before birth. The diagnosis and treatment of BA in a term infant was performed in the first 9 days of life with an excellent outcome. Analysis of λ-glutamyl transpeptidase enzyme levels in amniotic fluid provides further insight into the prenatal temporal onset of BA. These findings suggest that BA involves gradual biliary occlusion that may begin weeks before birth.
Intragroup dynamics of a cooperative breeder: An anlysis of reproductive roles in the acorn woodpecker

The acorn woodpecker is a cooperative breeder generally thought to breed promiscuously within groups, but alternative patterns of reproductive investment can be expected and remain to be examined. With this feature of mating system in mind, we studied the reproductive roles of individuals in a single group of this species in central coastal California over a three-year period. Particularly detailed observations were made in 1979, when the group consisted of two potentially breeding sibling males and a single breeding female. One male (298) contributed significantly more than ♂ 297 in virtually all aspects of nest and fledgling care. These include (1) feeding nestlings, (2) nest sanitation, (3) nocturnal incubation and brooding, (4) feeding fledglings, and (5) escorting fledglings. In the few observed and rarely occurring dominance interactions, ♂ 298 prevailed. These results suggest that ♂ 298 had a higher probability of fathering the group's two 1979 offspring than did his brother. Thus, the two males differed substantially in their parental roles within the group, and very likely in reproductive roles, also. At present stage of knowledge, monogamy in groups with one female and more than one potential reproductive male is no less likely than promiscuity. These findings are discussed with respect to the evolution of cooperative breeding in this species.
A New Mouse Model in which the Proximal Tandem Ig Element of Titin is Truncated (IGKO) - Assessment of Diastolic Function

Titin is a giant protein that functions as a molecular spring and contributes to the passive diastolic stiffness of the left ventricle (LV). Titin's spring region consists of three sequence elements: the tandem Ig, the N2B and the PEVK elements. Mouse models exist in which either of the latter two elements (N2B KO, PEVK KO) has been deleted, but considering that these elements are also likely to play roles in signaling, we made a model in which we deleted 2/3 of the proximal tandem Ig element (IGKO), a region that is not known to contain signaling functions. Homozygous KO mice survive to adulthood and are fertile with no change in LV Weight to Body Weight (LVW/BW) ratio (3.67±0.07mg/g WT vs 3.51±0.04mg/g IgKO). A custom titin exon microarray confirmed the deletion of the expected exons with no other changes. Gel electrophoresis showed that the IGKO expresses an 88kDa smaller titin isoform but no other changes in isoform expression. Immuno-electron microscopy indicates that the remaining spring elements extend to a higher degree than in WT myocardium. Mechanical measurements in cardiomyocytes (see also poster by Methawasin) and myofibers show that the deletion increases passive stiffness in titin in a sarcomere length dependence manner, without adaptations in the passive stiffness of the extracellular matrix. Initial isolated intact heart data and in-vivo pressure volume measurement suggest that the IGKO has increased stiffness in-vivo. Further phenotypic characterization is currently underway. In summary, shortening the proximal tandem Ig element of titin produces a diastolic stiffness phenotype.
Successful conservative management of nephrocolic fistula.

We present a case of an inflammatory nephrocolic fistula treated successfully with conservative management.
JUSTIFICATION FOR DIRECT REGULATION OF CONSUMER CREDIT REAPPRAISED (Discussion)

PROFESSOR BARTELS HAS CITED four basic assumptions which he feels underlie the reasoning of those who have supported publicly the regulation of consumer credit. It is the contention of the remarks to follow that three of the assumptions cited are not essential to the case for the selective control of consumer credit as seen by this observer. The other assumption, which must be accepted, is seen as a basic proposition in the study of the economics of consumer credit and one which I do not believe Professor Bartels intends to refute. Although Professor Bartels' compelling analysis may remove the ground from under many of the regulation's adherents, the basic case for restoration of the right to regulate consumer credit, as I see it, remains unimpaired. Since Professor Bartels' method is to illustrate that the facts of consumer credit do not verify these assumptions, it seems pertinent to re-examine these assumptions in order to see whether or not they are necessary. The first assumption listed was "that a consumer's normal purchasing power is increased by his use of credit." Mathematically, I think most of us will agree that I can purchase more, immediately, with credit than without credit. Over a longer period of time some people say that the consumer has less purchasing power since if the consumer saved to purchase goods without credit he would not have to pay interest charges thereby retaining greater purchasing power. To accept this argument one would have to assume that income must remain constant and that time is a commodity not worth purchasing. Since others have discovered that in the past consumer credit has played an important part in raising our national living standard and I believe will continue to do so in the future, the assumption that income is unaffected by the use of credit appears unrealistic. The observation that the use of consumer credit may raise national income may be seen in the writings of such pioneers in the literature of consumer credit as Alvin Johnson, Edwin R. A.
Semileptonic Decay of Charmed Particles and Weak Form-Factors

We present a phenomenological analysis of semileptonic decays of charmed particles based on SU(4) symmetry and (axial-) vector-meson dominance of weak form factors. The modified monopole form factors, which have been recently discussed by Sehgal, are extensively applied for charmed-particle decays throughout this work. These form factors contain an as yet undetermined parameter. We find a precise quantitative relation, depending on this parameter, between semileptonic decay rates and production cross sections of charmed baryons in neutrino-induced quasielastic scattering. The preliminary data on the latter processes suggest that either (i) form factors decrease in the spacelike region much faster than previously expected, or (ii) the Cabibbo factor is considerably smaller than the conventional value assumed for production processes of charmed baryons, i.e., sin/sup 2/theta<<0.05. We also discuss a few methods to test the basic hypotheses underlying this work.
Volume rendering of heart muscle mitochondria

Volumetric representations of electron microscopy reveal nanometer structural features of the mitochondrion. These organelles are the cell's 'power plant,' generating most of the adenosine triphosphate - the main source of chemical energy for a cell. Visualized here are the mitochondria present in human heart muscle. A texture-based volume rendering engine, named Cyclops and developed by Chris Burns while at the Texas Advanced Computing Center illuminate the structure of these organelles. Data was provided by Chris Gilpin at the University of Texas Southwestern Medical Center in Dallas, Texas. Volume rendering was performed in real-time on the Longhorn Visualization and Data Analysis cluster at the Texas Advanced Computing Center.
Triiodothyronine potentiates the stimulatory effects of interleukin‐1β on bone resorption and medium interleukin‐6 content in fetal rat limb bone cultures

It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3'-triiodothyronine (T 3 ) on bone resorption ( 45 Ca release) and on the IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T 3 alone increased 45 Ca release significantly only at a fairly high concentration (10 -6 M) under the conditions used. T 3 alone, over a 10 -11 -10 -6 M concentration range, failed to elicit a detectable effect on the medium IL-6 content. However, T 3 potentiated the stimulatory effect of interleukin-1β (IL-1β) on IL-6 production in a dose-dependent manner. T 3 , 10 -8 M, also significantly increased IL-1β-stimulated calcium release. Inhibition of IL-1β with 1 μM interleukin-1 receptor antagonist (IL-1ra) abrogated the potentiating effects of T 3 on IL-1β-stimulated IL-6 production and blocked the combined effect of T 3 and IL-1β on 45 Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL-1β, as well as the combined effect of IL-1β and T 3 on resorption and IL-6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 μM prostaglandin E 1 (PGE 1 ) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1β, T 3 increased bone resorption at much lower concentrations. We therefore speculate that the enhancement of IL-1β effects may be a biologically relevant mechanism of thyroid hormone action on bone.
Structural Effects of an LQT-3 Mutation on Heart Na+ Channel Gating

Computational methods that predict three-dimensional structures from amino acid sequences have become increasingly accurate and have provided insights into structure-function relationships for proteins in the absence of structural data. However, the accuracy of computational structural models requires experimental approaches for validation. Here we report direct testing of the predictions of a previously reported structural model of the C-terminus of the human heart Na+ channel. We focused on understanding the structural basis for the unique effects of an inherited C-terminal mutation (Y1795C), associated with long QT syndrome variant 3 (LQT-3), that has pronounced effects on Na+ channel inactivation. Here we provide evidence that this mutation, in which a cysteine replaces a tyrosine at position 1795 (Y1795C), enables the formation of disulfide bonds with a partner cysteine in the channel. Using the predictions of the model, we identify the cysteine and show that three-dimensional information contained in the sequence for the channel protein is necessary to understand the structural basis for some of the effects of the mutation. The experimental evidence supports the accuracy of the predicted structural model of the human heart Na+ channel C-terminal domain and provides insight into a structural basis for some of the mutation-induced altered channel function underlying the disease phenotype.
Enantioselective Catalysis of the Aza-Cope Rearrangement by a Chiral Supramolecular Assembly

The chiral supramolecular catalyst Ga4L6 [L = 1,5-bis(2,3-dihydroxybenzoylamino)naphthalene] is a molecular tetrahedron that catalyzes the 3-aza-Cope rearrangement of allyl enammonium cations. This catalysis is accomplished by preorganizing the substrate in a reactive conformation within the host. This work demonstrates that through the use of enantiopure assembly, its chiral cavity is capable of catalyzing the 3-aza-Cope rearrangement enantioselectively, with yields of 21−74% and enantiomeric excesses from 6 to 64% at 50 °C. At lower temperatures, the enantioselectivity improved, reaching 78% ee at 5 °C. This is the highest enantioselectivity to date induced by the chiral cavity of a supramolecular assembly.
An application of sequential analysis to observer-based psychophysics

Sequential analysis, a statistical technique developed during World War II, is shown to have direct applications to certain observer-based psychophysical procedures. This article shows how a particular sequential analysis procedure (the sequential probability ratio test) can be used to collect and analyze the data generated during observer-based psychophysics. It also provides an indication of the savings in numbers of observations (about 50%) that can be expected when sequential analysis is used in this way.
An improved constitutive model for concentrated suspensions accounting for shear-induced particle migration rate dependence on particle radius

Several rheological constitutive equations for the modeling of dense suspensions in nonlinear shear flows have been developed over the last three decades. Although these models have been able to predict the correct steady-state solid-phase concentration profile, none have been able to follow the transient experimentally measured concentration profile over a range of suspended particle radii with a consistent set of diffusion coefficients. In this research, two improvements are made to the diffusive-flux model, namely, modeling the diffusion coefficients as linear functions of the so-called nonlinearity parameter and adding slip boundary conditions at the wall. A particle-level explanation for the linear dependence of the diffusion coefficients on the nonlinearity parameter is provided. With these two improvements, it is shown that the modified diffusive flux model can accurately predict the transient solid-phase concentration profile in a Couette device over a wide range of particle radii.
Transcriptional and Epigenetic Regulation of Neural Crest Induction during Neurulation

Neurulation is one of the many important events in mammalian development. It is the stage of organogenesis in vertebrate embryos during which the neural tube is transformed into the primitive structures that will later develop into the central nervous system. Recent transcriptome analysis during neurulation and early organogenesis in humans and mice has identified the global dynamics of gene expression changes across developmental time. This has revealed a richer understanding of gene regulation and provides hints at the transcriptional regulatory networks that underlie these processes. Similarly, epigenome analysis, which collectively constitutes histone modifications, transcription factor binding, and other structural features associated with gene regulation, has given a renewed appreciation to the subtle mechanisms involving the process of neurulation. More specifically, the histone demethylases KDM4A and KDM6B have recently been shown to be key histone H3K4 and H3K27 modifiers that regulate neural crest specification and neural tube closure. Additionally, miRNAs have recently been shown to influence transcription of genes directly or by altering the levels of epigenetic modifiers and thus regulate gene expression. This mini review briefly summarizes the literature, highlighting the transcriptional and epigenetic regulation of key genes involved in neural crest induction and neural crest specification by transcription factors and miRNAs. Understanding how these mechanisms work individually and in clusters will shed light on pathways in the context of diseases associated with neural crest cell derivatives such as melanoma, cardiovascular defects and neuronal craniofacial defects.
Observations on ectodesmata and the virus infection process

Ectodesmata were visualized in outer epidermal cell walls of Nicotiana tabacum (L.) var. T.I. 787 by means of a silver nitrate stain and electron microscopy. After inoculation of potato virus X (PVX), neither whole virus nor viral RNA could be observed in ectodesmata by means of direct observations in the electron microscope. Fully assembled virus particles were seen attached to, but not penetrating, the cuticle of inoculated tobacco leaves.
The impact of discussion on interpersonal attraction

The effects of similarity, format of presentation, and choice of topics for attitude exchange on interpersonal-attraction ratings was investigated in this study. Subjects met and exchanged views on six of eight high-interest attitude items in a 2 x 2 x 2 factorial design. Half of the sub­ jects were allowed to discuss their views, whereas the other half read their responses from an attitude booklet. High-similarity (67%-agreement) and low-similarity (33%-agreement conditions were crossed with the format conditions. Furthermore, subjects were either allowed or not allowed to choose the six items for exchange. Main effects were found for similarity and for format of presentation, but not for choice of topics for the attraction ratings. Subjects also re­ ported greater satisfaction with the discussion format.
The radiative capture reactions 40Ca(α, γ)44Ti and 48Ca(α, γ)52Ti in the region of the giant dipole resonance

Abstract An investigation of the reactions 40Ca(α,γ)44Ti and 48Ca(α,γ)52Ti in the region of the giant dipole resonance (GDR) has been completed. For the 40Ca(α,γ) reaction, 90° excitation functions over the bombarding energy range 6.5–17.5 MeV were obtained for γ- transitions to the ground state and first excited state in 44Ti and for a sum of the unresolved transitions to the third and fourth excited states in 44Ti. Angular distributions were measured at the extrema of the excitation functions. These data suggest that the 40Ca(α,γ) reaction proceeds predominantly via an isospin forbidden El transition and populates the T = 1, GDR states of 44Ti via T = 0 isospin impurities. The results provide an estimate of the isospin mixing in the GDR as well as support for a possible giant quadrupole resonance somewhat lower in excitation energy in 44Ti. The excitation functions exhibit a gross structure which reflects the isospin mixing in the GDR of 44Ti, and a structure of intermediate width which may reflect T = 0 α- cluster states in 44Ti. The 48 Ca (α,γ o ) differential cross section was investigated at 90° over the bombarding energy range 6.0–14.0 MeV. The cross section for the isospin allowed 48 Ca (α γ 0 ) reaction was found to be a factor of 20 smaller than that for the isospin forbidden 40 Ca (α,γ 0 ) reaction.
Effect of stimulus presentation rate upon visual threshold

Abstract Threshold measurements during dark adaptation are shown to be affected by the rate at which the threshold stimuli are presented. Thresholds for rods and for peripheral cones are raised by higher stimulus presentation rates, but thresholds for foveal cones are not. This difference for cones implies a previously unrecognized mechanism of visual sensitivity. The results are compared with the Troxler fading effect, and with earlier studies of light adaptation to intermittent stimuli.
Uses and abuses of Amdahl's law

Amdahl's law has been widely used by designers and researchers to get a rough estimate of performance improvement when alternate designs and implementations are attempted. It gives a simple relationship between the nature of performance improvement and the problem characteristics. The negative way the original law was stated [Amd67] contributed to a good deal of pessimism about the nature of parallel processing. But, after observing remarkable speedups in some large-scale applications, researchers in parallel processing started wrongfully suspecting the validity and usefulness of Amdahl's law. In this paper we present the many uses of Amdahl's law as well as some of its abuses.
The rational use of antibiotics in bacterial infection

Abstract Antibiotics are among the most commonly prescribed and misused drugs in paediatrics. Their clinical use inevitably drives the evolution of bacterial resistance. This has set new challenges to their rational use, the essence of which is to try to minimize the emergence and spread of resistance whilst achieving the best possible clinical response. Judicious antibiotic use will also reduce side-effects and cost.
Murine pharmacokinetics and metabolism of penclomedine [3,5-dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine, NSC 338720].

Abstract Penclomedine, a highly substituted pyridine derivative, has been selected by the National Cancer Institute for evaluation as a potential anticancer agent based on antitumor activity observed in murine tumor models following i.v., p.o., and i.p. administration. We have developed a reverse-phase high performance liquid chromatography assay for PEN, and subsequently investigated murine pharmacokinetics and metabolism. Following rapid i.v. injection of PEN (300 mg/m 2 ) to mice, plasma elimination was best described by a 2-compartment open model with an elimination phase half-life, total body clearance, and steady-state distribution volume of 69 min, 114 ml/min/m 2 , and 4800 ml/m 2 , respectively. While PEN displayed good p.o. absorption, bioavailability of PEN after p.o. administration was approximately 2% of that observed following i.v. administration. Metabolism contributed substantially to drug clearance, and total metabolites were slowly eliminated from plasma. After i.v. and p.o. administration of radiolabeled PEN,
Influence of membrane surface properties on initial rate of colloidal fouling of reverse osmosis and nanofiltration membranes

Abstract Recent studies have shown that membrane surface morphology and structure influence permeability, rejection, and colloidal fouling behavior of reverse osmosis (RO) and nanofiltration (NF) membranes. This investigation attempts to identify the most influential membrane properties governing colloidal fouling rate of RO/NF membranes. Four aromatic polyamide thin-film composite membranes were characterized for physical surface morphology, surface chemical properties, surface zeta potential, and specific surface chemical structure. Membrane fouling data obtained in a laboratory-scale crossflow filtration unit were correlated to the measured membrane surface properties. Results show that colloidal fouling of RO and NF membranes is nearly perfectly correlated with membrane surface roughness, regardless of physical and chemical operating conditions. It is further demonstrated that atomic force microscope (AFM) images of fouled membranes yield valuable insights into the mechanisms governing colloidal fouling. At the initial stages of fouling, AFM images clearly show that more particles are deposited on rough membranes than on smooth membranes. Particles preferentially accumulate in the “valleys” of rough membranes, resulting in “valley clogging” which causes more severe flux decline than in smooth membranes.
THE “PUSH” FOR EVIDENCE: MANAGEMENT OF THE SECOND STAGE

Recognition that the available evidence does not support arbitrary time limits for the second stage of labor has led to reconsideration of the influence of maternal bearing down efforts on fetal/newborn status as well as on maternal pelvic structural integrity. The evidence that the duration of ‘active’ pushing is associated with fetal acidosis and denervation injury to maternal perineal musculature has contributed to the delineation of at least two phases during second stage, an early phase of continued fetal descent, and a phase of “active” pushing. The basis for the recommendation that the early phase of passive descent be prolonged and the phase of active pushing shortened by strategies to achieve effective, but non-detrimental pushing efforts is reviewed. The rational includes an emphasis on the obstetric factors that are optimal for birth and conducive to efficient maternal bearing down. Explicit assessment of these obstetric factors and observation of maternal behavior, particularly evidence of an involuntary urge to push, should be coupled with the use of maternal positions that will promote fetal descent as well as reduce maternal pain. The use of epidural analgesia for pain relief can also be accompanied by these same principles, although further research is needed to verify the strategies of “delayed pushing” and maintenance of pain relief along with a reconceptualization of the second stage of labor.
School-aged Children's Perception of Stress in the Hospital

This article is based on a research study of hospitalized school-aged children's perception of stress. Forty-two different stimuli were identified through the use of a projective-type game developed by the investigator. The findings of the study did not support the hypotheses that there is a relationship between the stimuli that children perceive as stressful and their preparation for hospitalization nor their length of time in the hospital.
At Home in the Seamless Web: Agency, Obduracy, and the Ethics of Metropolitan Growth

Political responses to metropolitan growth in the United States and elsewhere should include careful ethical deliberation, but ethical judgment and action are limited by the involvement of individual moral agents in the complex processes that give shape to the built environment. I propose that casting the built environment as a heterogeneous sociotechnical ensemble can provide useful insight into the limits of ethics, particularly through the concept of obduracy. To the extent components of an ensemble are obdurate, they can stop or deflect even well-considered actions even as they impose constraints on moral agency itself. From this possibility spring a number of worthwhile lines of inquiry at the confluence of ethics and technology studies.