cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence for Physical Association of Mitochondrial Fatty Acid Oxidation and Oxidative Phosphorylation Complexes

Fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are key pathways involved in cellular energetics. Reducing equivalents from FAO enter OXPHOS at the level of complexes I and III. Genetic disorders of FAO and OXPHOS are among the most frequent inborn errors of metabolism. Patients with deficiencies of either FAO or OXPHOS often show clinical and/or biochemical findings indicative of a disorder of the other pathway. In this study, the physical and functional interactions between these pathways were examined. Extracts of isolated rat liver mitochondria were subjected to blue native polyacrylamide gel electrophoresis (BNGE) to separate OXPHOS complexes and supercomplexes followed by Western blotting using antisera to various FAO enzymes. Extracts were also subjected to sucrose density centrifugation and fractions analyzed by BNGE or enzymatic assays. Several FAO enzymes co-migrated with OXPHOS supercomplexes in different patterns in the gels. When palmitoyl-CoA was added to the sucrose gradient fractions containing OXPHOS supercomplexes in the presence of potassium cyanide, cytochrome c was reduced. Cytochrome c reduction was completely blocked by myxothiazol (a complex III inhibitor) and 3-mercaptopropionate (an inhibitor of the first step of FAO), but was only partially inhibited by rotenone (a complex I inhibitor). Although palmitoyl-CoA and octanoyl-CoA provided reducing equivalents to OXPHOS-containing supercomplex fractions, no accumulation of their intermediates was detected. In contrast, short branched acyl-CoA substrates were not metabolized by OXPHOS-containing supercomplex fractions. These data provide evidence of a multifunctional FAO complex within mitochondria that is physically associated with OXPHOS supercomplexes and promotes metabolic channeling.
KCNE1 Slows the Voltage Sensors of KCNQ1

KCNQ1 α-subunits assemble with KCNE1 forming the slow cardiac potassium channel IKs. KCNE1 alters currents of α-subunits by slowing activation and deactivation kinetics, suppressing inactivation, and increasing single-channel conductance. Attempts to elucidate the mechanism of KCNE1-induced slowing of kinetics have come to discrepant conclusions. Two studies using chemical modifiers and cys-substitution in the KCNQ1 S4 supported one model where KCNE1 acts on voltage-sensors alone and another where only the activation-gate is affected. A fluorimetric study argued for effects on sensors and the gate (Osteen et al, PNAS 2010). To address the controversy, we used cut-open oocyte vaseline-gap clamp to record gating currents, ionic currents and perform site-directed, voltage-clamp fluorimetry (VCF).Gating currents show that voltage-sensor movement precedes pore opening in channels with only KCNQ1 α-subunits. VCF confirms this result. While ionic currents have a lag before activation, gating and fluorescence changes do not; this indicates a final concerted step after voltage sensors move before pore opening. In contrast, channels with KCNE1 show voltage-sensor movements with no lag that are ∼20-fold slower and mirror slowing of ionic current activation. These findings are unlike those made by Osteen et al. We used a smaller dye inserted closer to S4 and measured ionic current and fluorescence simultaneously in the same cells. We observe a matching and expected shift in the IKs fluorescence-voltage and ionic current-voltage relationships of +50 mV with KCNE1 and do not see voltage-sensor movements at hyperpolarized voltages as they report.Both KCNQ1 and IKs channels have voltage-sensor kinetics almost as slow as ionic activation. Our simultaneous kinetic recordings of fluorescence and ionic currents support a model in which IKs channels are slowed purely by an effect of KCNE1 on the KCNQ1 voltage sensors. Support: HL105949 and GM030376.
Facts and fiction surrounding the discovery of the venous valves.

Abstract Venous valves are delicate structures, the integrity of which is crucial for the normal function of the venous system. Their abnormalities lead to widespread disorders, ranging from chronic venous insufficiency to life-threatening thromboembolic phenomena. The discovery of the venous valves, however, has been the subject of hot controversy. Even though Fabricius ab Aquapendente is credited with the discovery by most historians, we demonstrate in this paper that other anatomists described them many years before Fabricius ab Aquapendente publicly demonstrated them in Padua in 1579. A thorough review of the historical literature surrounding the discovery of the venous valves was carried out from 1545 to the present under the supervision of the Medical History Department of our institution. Research was performed at the History of Medicine Division of the National Library of Medicine and through MEDLINE access to the medical literature. The Parisian Charles Estienne first mentioned the venous valves in his 1545 publication when he described "apophyses membranarum" in the veins of the liver. Lusitanus and Canano publicly demonstrated them in the azygos vein during cadaver dissections performed in Ferrera, Italy. The Parisian Jacques Sylvius described valves in the veins of the extremities in 1555. The work of these anatomists, however, could not achieve full recognition, because Andreas Vesalius, the leading anatomist at that time, was unable to confirm their findings and strongly denied the existence of venous valves. Vesalius's influence was so powerful that research on the subject was idle until 1579, when Fabricius ab Aquapendente "discovered" the venous valves. About the same time, the German Salomon Alberti published the first drawings of a venous valve (in 1585). William Harvey, a disciple of Fabricius ab Aquapendente, finally postulated the function of the venous valves, providing anatomical support for one of the greatest discoveries in medicine: the blood circulation. Therefore, our investigations revealed that Estienne and Canano discovered the venous valves in the 1530s. Fabricius ab Aquapendente's achievement was their full recognition 64 years later. However, it was not until 1628 that their function was fully understood, with the discovery of the blood circulation by William Harvey. (J Vasc Surg 2001;33:435-41.)
Format recognition: A report of a project at the library of congress†

An experiment using a computer to assign content designators to unedited machine readable bibliographic data to create MARC records is described. Input typing conventions are briefly discussed. A computer program (Assembler Language for DOS) is being developed which analyzes unedited data according to predefined algorithms and builds MARC records. A manual simulation using 150 catalog records was done to test the computer algorithms. The results of the test in terms of accuracy and throughput compared favorably with the current MARC input system in use at the Library of Congress.
Teaching partner-focused questions to individuals who use augmentative and alternative communication to enhance their communicative competence.

A single-subject, multiple-probe experimental design was used to investigate the effect of instruction on the acquisition, generalization, and long-term maintenance of partner-focused questions (i....
The evolution of the rules and regulations of the first emerging markets: the London, New York and Paris stock exchanges, 1792–1914

Abstract Emerging stock markets present special problems for regulators, given that any stock exchange operates with a cooperative group of members whose collective interests at times may conflict with either the goals of investors or of corporations placing their securities on the market. Examining the distinct histories of the rules and regulations of the first emerging markets of the 19th century – London, New York, and Paris – we conclude that the rules established by the initial group of members in an exchange determine how it functions thereafter. Turning to recent experiences with stock exchanges in central and east Europe and in Asia, it appears that many of the lessons learned in the 19th century have been neglected in setting up the emerging markets of the 1990s.
Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists

Investigation of a series of heterobicyclic compounds with essential pharmacophoric features of the metabotropic glutamate receptor 5 (mGluR5) antagonists MPEP and MTEP provided novel structural templates with sub-micromolar affinities at the mGluR5.
Supervisory neglect and adolescent alcohol use disorders: effects on AUD onset and treatment outcome.

Abstract Background While parental supervision has been demonstrated to influence adolescent alcohol involvement, lack of a threshold defining inadequate supervision and little study of DSM defined alcohol use disorders (AUDs) have limited clinical applications. Utilizing a four-item supervision scale, this study identified adolescents with inadequate supervision, and examined effects on AUD development and treatment outcome. Methods Two groups of adolescent subjects (ages 14–17) were recruited: (1) a representative community sample of adolescents (n = 170) and (2) adolescents with AUDs from drug and alcohol or psychiatric treatment programs (n = 194). Supervision was determined by the adolescent's responses to items inquiring whether parents typically had knowledge of the adolescent's activities away from home, including with whom, where, when, and communication items. Adolescents with unusually low parental supervision (i.e., Supervisory Neglect) were identified by scale distributions. Follow-up assessments were conducted 1, 3, and 5 years after the initial assessment. Results Among community subjects, adolescents with inadequate supervision were significantly more likely to drink alcohol in a variety of situations, were more likely to have AUDs at the initial assessment and, among those without AUDs, were more likely to develop AUDs in the follow-up period. Among adolescents receiving treatment for AUDs, those with inadequate supervision were less likely to be free of AUD symptoms over a 1-year follow-up period. Conclusions These results indicate that the described method was a straightforward and potentially clinically applicable approach to identifying adolescents with inadequate parental supervision.
Paper: Bluestein's FFT for arbitrary N on the hypercube

The original Cooley-Tukey FFT was published in 1965 and presented for sequences with length N equal to a power of two. However, in the same paper they noted that their algorithm could be generalized to composite N in which the length of the sequence was a product of small primes. In 1967, Bergland presented an algorithm for composite N and variants of his mixed radix FFT are currently in wide use. In 1968, Bluestein presented an FFT for arbitrary N including large primes. However, for composite N, Bluestein's FFT was not competitive with Bergland's FFT. Since it is usually possible to select a composite N, Bluestein's FFT did not receive much attention. Nevertheless because of its minimal communication requirements, the Bluestein FFT may be the algorithm of choice on multiprocessors, particularly those with the hypercube architecture. In contrast to the mixed radix FFT, the communication pattern of the Bluestein FFT maps quite well onto the hypercube. With P = 2^d processors, an ordered Bluestein FFT requires 2d communication cycles with packet length N/2P which is comparable to the requirements of a power of two FFT. For fine-grain computations, the Bluestein FFT requires 20log"2N computational cycles. Although this is double that required for a mixed radix FFT, the Bluestein FFT may nevertheless be preferred because of its lower communication costs. For most values of N it is also shown to be superior to another alternative, namely parallel multiplication.
Stress-System Genes and Life Stress Predict Cortisol Levels and Amygdala and Hippocampal Volumes in Children

Depression has been linked to increased cortisol reactivity and differences in limbic brain volumes, yet the mechanisms underlying these alterations are unclear. One main hypothesis is that stress causes these effects. This is supported by animal studies showing that chronic stress or glucocorticoid administration can lead to alterations in hippocampal and amygdala structures. Relatedly, life stress is cited as one of the major risk factors for depression and candidate gene studies have related variation in stress-system genes to increased prevalence and severity of depression. The present study tested the hypothesis that genetic profile scores combining variance across 10 single nucleotide polymorphisms from four stress-system genes (CRHR1, NR3C2, NR3C1, and FKBP5) and early life stress would predict increases in cortisol levels during laboratory stressors in 120 preschool-age children (3–5 years old), as well as hippocampal and amygdala volumes assessed with MRI in these same children at school age (7–12 years old). We found that stress-system genetic profile scores positively predicted cortisol levels while the number of stressful/traumatic life events experienced by 3–5 years old negatively predicted cortisol levels. The interaction of genetic profile scores and early life stress predicted left hippocampal and left amygdala volumes. Cortisol partially mediated the effects of genetic variation and life stress on limbic brain volumes, particularly on left amygdala volume. These results suggest that stress-related genetic and early environmental factors contribute to variation in stress cortisol reactivity and limbic brain volumes in children, phenotypes associated with depression in adulthood.
Delay-discounting probabilistic rewards: Rates decrease as amounts increase.

The independence of delay-discounting rate and monetary reward size was tested by offering subjects (N = 621) a series of choices between immediate rewards and larger, delayed rewards. In contrast to previous studies, in which hypothetical rewards have typically been employed, subjects in the present study were entered into a lottery in which they had a chance of actually receiving one of their choices. The delayed rewards were grouped into small ($30-$35), medium ($55-$65), and large amounts ($70-$85). Using a novel parameter estimation procedure, we estimated discounting rates for all three reward sizes for each subject on the basis of his/her pattern of choices. The data indicated that the discounting rate is a decreasing function of the size of the delayed reward (p < .0001), whether hyperbolic or exponential discounting functions are assumed. In addition, a reliable gender difference was found (p = .005), with males discounting at higher rates than females, on average.
2-Aminopurine Excited State Electronic Structure Measured by Stark Spectroscopy

2-Aminopurine (2AP) is an adenine analogue that has a high fluorescence quantum yield. Its fluorescence yield decreases significantly when the base is incorporated into DNA, making it a very useful real-time probe of DNA structure. However, the basic mechanism underlying 2AP fluorescence quenching by base stacking is not well understood. A critical element in approaching this problem is obtaining an understanding of the electronic structure of the excited state. We have explored the excited state properties of 2AP and 2-amino,9-methylpurine (2A9MP) in frozen solutions using Stark spectroscopy. The experimental data were correlated with high level ab initio (MRCI) calculations of the dipole moments, mu0 and mu1, of the ground and excited states. The magnitude and direction of the dipole moment change, Deltamu01 = mu1 - mu0, of the lowest energy optically allowed transition was determined. While other studies have reported on the magnitude of the dipole moment change, we believe that this is the first report of the direction of Deltamu, a quantity that will be of great value in interpreting absorption spectral changes of the 2AP chromophore. Polarizability changes due to the transition were also obtained.
Improving Control Performance by Minimizing Jitter in RT-WiFi Networks

Wireless networked control systems have received significant attention due to their great advantages in enhanced system mobility, and reduced deployment and maintenance cost. To support a wide range of high-speed wireless control applications, we presented in our prior work the design and implementation of a flexible real-time high-speed wireless communication platform called RT-WiFi. RT-WiFi currently provides up to 6kHz sampling rate and deterministic timing guarantee on packet delivery. While guaranteed delivery latency is essential for networked control, control performance is also impacted by communication jitter and other QoS parameters. To reduce jitter, a flexible network manager is needed to control network-wide scheduling of packet transportation. In this paper, we present an RT-WiFi network manager design and propose efficient solutions for two fundamental RT-WiFi network management problems. To improve control performance in networked control systems, our RT-WiFi network manager is designed to generate data link layer communication schedule with minimum jitter under both static and dynamic network topologies. In order to minimize network management overhead, an efficient data structure called S-tree is invented to manage the communication requests to deal with network dynamics. We have implemented the RT-WiFi network manager, and validated its network and control performance through extensive experiments with a real application.
Cocaine alters the onset and maintenance of maternal behavior in lactating rats.

Abstract Though much attention has been devoted to the behavioral and physiological consequences of cocaine abuse in offspring, little is known regarding the effects on the maternal behavior of the cocaine-exposed dam. We examined whether cocaine affects the initiation (late pregnancy) and/or maintenance (postpartum [PP]) phases of full maternal behavior (FMB; retrieving, grouping, and crouching over six pups) in Sprague-Dawley female rats. In Experiment 1, cocaine (5.0 or 10.0 mg/ kg) or saline was administered on PP day 5 or 6 and FMB scored. Both dosages significantly disrupted FMB, particularly crouching, though 10.0 mg/kg had a greater effect on FMB. Experiment 2 (using 10.0 mg/kg cocaine) examined specific elements of the disruption and found significant reductions in proportion of females engaging in FMB, as well as increases in the latencies to contact, retrieve, lick, group, and crouch over pups. In experiment 3 osmotic pumps containing 20 mg cocaine/kg/day or saline were implanted SC in day 14 pregnant rats. FMB testing was performed on days 1–2 postpartum together with a T-maze pup-retrieval test on postpartum days 3–5. Cocaine disrupted FMB in the homecage, in general, rendering the females less attentive to young, but was without effect in the T-maze tests. Cocaine-perhaps owing to its purported dopaminergic activity-may operate through motivational mechanisms to disrupt FMB in the postpartum maintenance phase; and through effects on late pregnancy levels of prolactin (a hormone which stimulates FMD), to disrupt maternal behavior during the initiation phase.
Detectability of extrasolar planetary transits

Precise stellar photometry can be used to detect other planetary systems. However, the intrinsic variability of stellar luminosity imposes a fundamental limit on the sensitivity of this method. Based on recent precise solar observations made from the Solar Maximum Mission satellite, it appears that the detection of earth-sized planets will be marginal during periods of high stellar activity. However, with a suitable photometer larger planets should be readily detectable even in the presence of stellar activity equal to that of the sun at the peak of its sunspot cycle. The high precision, multiple-star photometric system required to detect planets in other stellar systems could be used to monitor flares, starspots, and global oscillations.
Influences of weather on reproductive function in male Song sparrows, Melospiza melodia

Prolonged and severe periods of inclement weather can retard gonadal development in early spring or disrupt the breeding cycle in summer. Previous investigations on the endocrine responses of free-living avian species to storms have been restricted almost entirely to males. This communication presents the endocrine responses of free-living female Song sparrows, Melospiza melodia, during gonadal recrudescence after a severe winter, and during storms in early spring and summer. As in males, gonadal recrudescence was delayed by the severe winter weather, and this effect was exacerbated by an aseasonal snow storm in early spring. Unlike males, female Song sparrows did appear to be stressed by this snow storm, since body mass and fat deposit decreased, and plasma levels of corticosterone increased. A second storm in early summer did not, however, prove to be stressful to females, although males were apparently stressed by the same storm. At the time the early summer storm occurred, young had been fledged and were being fed mostly by the male. Females begin preparing for a second clutch of eggs and do not feed fledglings to the same extent as males. Thus it is possible that males are stressed by storms at this time, because they are feeding several young as well as themselves during a period of reduced availability of food, whereas females are feeding themselves only. These data suggest that, not only do the endocrine responses to inclement weather vary in relation to stage in the reproductive cycle when storms strike, but also that there are sex differences in those responses.
A RAPID MASS SPECTROMETRIC METHOD FOR THE SIMULTANEOUS ANALYSIS OF BARIUM,CADMIUM, AND STRONTIUM IN FORAMINIFERA SHELLS

Abstract Recent developments in inductively coupled plasma mass spectrometry (ICP-MS) make it possible to simultaneously measure a suite of trace elements of paleoceanographic interest in foraminifera shells from deep-sea sediments. Here we present an ICP-MS method that allows determination of precise Cd/Ca, Ba/Ca, Sr/Ca and Mn/Ca ratios in purified foraminifera shell samples as small as 25 μg. The method utilizes a combination of isotope dilution for Ba and Cd determination and internal standardization for Ca and Sr determination. Long term reproducibility of the method is 2–3% for the elemental ratios. The principal advantages of the method are that all four elemental ratios of paleoceanographic interest are generated simultaneously for a single sample of purified foraminiferal carbonate, minimizing sample size requirement, reducing analysis time, and improving correlation between proxies.
Photochemical Upconversion: A Physical or Inorganic Chemistry Experiment for Undergraduates Using a Conventional Fluorimeter

Photochemical upconversion is a regenerative process that transforms lower-energy photons into higher-energy light through two sequential bimolecular reactions, triplet sensitization of an appropriate acceptor followed by singlet fluorescence producing triplet–triplet annihilation derived from two energized acceptors. This laboratory directly investigates this phenomenon using the facile photo-induced triplet–triplet energy-transfer reaction between the benchmark inorganic chromophore tris(2,2′-bipyridyl)ruthenium(II), [Ru(bpy)3]2+, and 9,10-diphenylanthracene (DPA). Selective green excitation of [Ru(bpy)3]2+ in the presence of DPA results in two observations, the (dynamic) quenching of the [Ru(bpy)3]2+ photoluminescence in the red and the production of upconverted DPA singlet fluorescence in the blue. The quadratic nature of the incident light power dependence for the latter process is easily realized by using the percent transmission characteristics of neutral density filters placed in the excitation be...
Dynamic High-Resolution 3-D Photoacoustic Microscopy with Cylindrically Focused Optical Illumination

We developed ultrasound-array-based photoacoustic microscopy capable of 2-D and 3-D imaging at 249 and 0.5 Hz, respectively. With cylindrically focused optical illumination, it achieved 28-micron elevational-resolution, enabling dynamic high-resolution 3-D imaging of microvasculature in vivo.
Neurophysiology of cochlear implant users I: effects of stimulus current level and electrode site on the electrical ABR, MLR, and N1-P2 response.

Objective As the need for objective measures with cochlear implant users increases, it is critical to understand how electrical potentials behave when stimulus parameters are systematically varied. The purpose of this study was to record and evaluate the effects of implanted electrode site and stimulus current level on latency, amplitude, and threshold measures of electrically evoked auditory potentials, representing brainstem and cortical levels of the auditory system. Design The electrical auditory brainstem response (EABR), electrical auditory middle latency response (EAMLR), and the electrical late auditory response (ELAR) were recorded from the same experimental subjects, 11 adult Clarion cochlear implant users. The Waves II, III, and V of the EABR, the Na-Pa complex of the EAMLR and the N1-P2 complex of the ELAR were investigated relative to electrode site (along the intra-cochlear electrode array) and stimulus current level. Evoked potential measures were examined for statistical significance using analysis of variance (ANOVA) for repeated measures. Results For the EABR, Wave V latency was significantly longer for the basal electrode (7) compared with the mid (4) and apical (1) electrodes. For the EAMLR and ELAR, there were no significant differences in latency by electrode site. For all subjects and each of the evoked potentials, the apical electrodes tended to have the largest amplitude and the basal electrodes the smallest amplitude, although amplitude differences did not reach statistical significance. In general, decreases in stimulus current level resulted in statistically significant decreases in the amplitude of Wave V, Na-Pa and N1-P2. The evoked potential thresholds for Wave V, Na-Pa, and N1-P2 were significantly higher for the basal Electrode 7 than for Electrodes 4 and 1. Conclusions Electrophysiologic responses of Waves II, III, and V of the EABR, Na-Pa of the EAMLR, and N1-P2 of the ELAR were characterized as functions of current level and electrode site. Data from this study may serve as a normative reference for expected latency, amplitude and threshold values for the recording of electrically evoked auditory brainstem and cortical potentials. Responses recorded from cochlear implant users show many similar patterns, yet important distinctions, compared with auditory potentials elicited with acoustic signals.
Human resource development for a community-based health extension program: a case study from Ethiopia

Introduction Ethiopia is one of the sub-Saharan countries most affected by high disease burden, aggravated by a shortage and imbalance of human resources, geographical distance, and socioeconomic factors. In 2004, the government introduced the Health Extension Program (HEP), a primary care delivery strategy, to address the challenges and achieve the World Health Organization Millennium Development Goals (MDGs) within a context of limited resources.
Antigenic gene products of bacteriophage T4 baseplates

Abstract Antibodies raised against isolated T4 precursor baseplates exponentially inactivated T4 phage. The target antigens of the killing antibody were different from the targets of serum raised against complete phage particles. To determine which of the fourteen species of baseplate structural proteins represented the target antigens, we examined cells infected with mutants defective in baseplate assembly. The major target antigen was associated with precursors of the outer arms of the mature baseplate. A candidate for the antigen was the gene 11 tail spike protein. Serum-blocking experiments with defective phage particles lacking the gene 11 protein indicated that it was the target of 85% of the neutralizing antibody in the serum. The remaining 15% of the neutralizing antibody was directed against the gene 12 protein, which forms the short baseplate fibers ( Kells and Haselkorn, 1974 ). Cells infected with temperature-sensitive mutants in gene 11 had significantly decreased levels of the target antigen, supporting its identification as the product of gene 11. Surprisingly, cells infected with amber mutants at three different sites in gene 11 all accumulated normal levels of the target antigens, suggesting that the gene 11 amber fragments are stable and fully antigenic. The gene 11 tail spike protein complexes with the gene 10 protein in the first reaction in baseplate arm formation and is present in all subsequent intermediates in baseplate assembly. Therefore, antibody against the gene 11 product provides an assay for the purification of each of the intermediate protein complexes in baseplate morphogenesis.
Optical figure testing of prototype mirrors for JPL's precision segmented-reflector program

JPL's PSR program is developing enabling technologies for large space telescopes employing segmented optics, and in particular, lightweight, thermally stable mirrors for telescopes operating at sub-mm wavelengths. JPL's vacuum cryointerferometric optical test facility includes a computer-controlled phase shifting interferometer operating at 10.59 microns and laser metrology for measurement of piston and absolute radius of curvature. The optical metrology has been integrated with a large vacuum chamber including a liquid nitrogen shroud capable of radiatively cooling 1.5 meter aperture mirrors down to 150 K. The facility is now being used to characterize prototype mirrors in both their room-temperature 'as-replicated' condition, and under orbital temperature conditions. The performance and limitations of the optical metrology hardware and software components are noted. Representative test results on prototype one meter-class composite mirrors being developed for PSR and related ground-based programs are also presented.
Stochastic model for the production of antibody-forming cells.

FOR some time it has been thought that the generation of antibody-forming cells (AFC) may involve an interaction between cell types1–3. We present here a stochastic model, based on a two-cell interaction system, for the production of AFC. The assumptions on which the model is based have chiefly come from an interpretation of two types of experimental data, each of which can yield information concerning the number of cells involved. The first is limiting dilution analysis, which is based on the Poisson probability distribution. The second is dose–response analysis, showing the relationship between lymphoid cell dose and the number of AFC generated. These types of experiments involve either the transfer of lymphoid cells to irradiated, compatible recipients or the growth of lymphoid cells in diffusion chamber cultures.
Designing for the automobile: The work of John Nolen at Myers Park (1911) and Venice (1926)

John Nolen, city planner and landscape architect, is one of a small number of early twentieth century American planners who addressed the widespread effect of the automobile. This paper traces the development of Nolen's approach to new settlement design through an analysis of his proposals for Myers Park (1911) and Venice (1926). The approach to highway configuration is described and analysed with illustrations to show the character of the roads developed. A detailed comparison of the two developments includes the consideration of the designer's approach to: street network; orientation; roadway allocation; street types; design speed; intersection design; parking strategy; walkability. The paper concludes with a review of the original designs and final built form and the character that the areas have today.
Optical correlator with extended depth of field

Abstract Preprocessing with a Fabry-Perot etalon in the image plane of an optical correlator is used to extend the depth of field of the instrument without reducing its selectivity. Experimental results are compared with the output of a classical correlator as well as with theory.
Regulation of MicroRNAs by Brahma-related Gene 1 (Brg1) in Smooth Muscle Cells

MicroRNAs are involved in phenotypic switching of smooth muscle cells (SMCs). Brg1-containing SWI/SNF chromatin-remodeling complexes also play an important role in controlling the phenotype of SMCs. We thus determined whether Brg1 influences the transcription of microRNAs in SMCs. Microarray and quantitative RT-PCR analysis of smooth muscle from mice harboring smooth muscle-specific deletion of Brg1 revealed altered expression of several microRNAs, including miRs-143/145 and miR-133. Ablation of Brg1 in SMCs in vitro either by expression of dominant negative Brg1 or Brg1 knock-out attenuated miRs-143/145 expression. Knockdown of serum response factor (SRF) in SMCs significantly reduced the expression levels of miRs-143/145 and miR-133, whereas knockdown of myocardin only attenuated miRs-143/145 expression. Myocardin induced expression of miRs-143/145 and miR-133a and increased SRF binding to these genes in 10T1/2 cells. This myocardin-mediated induction was attenuated by dominant negative Brg1. In Brg1-null SW13 cells, miRs-143/145 were dramatically induced by myocardin only in the presence of Brg1, whereas miR-133 was not induced by myocardin in a Brg1-dependent manner. Chromatin immunoprecipitation assays demonstrated that in the presence of Brg1, myocardin increased SRF binding to both the miRs-143/145 and miR-133a loci. Together, these data suggest a mechanism in which Brg1-containing SWI/SNF complexes are required for myocardin to induce expression of miRs-143/145 in smooth muscle cells. In contrast, miR-133 expression appears to be regulated by Brg1-containing chromatin remodeling complexes in a partially SRF-dependent, although largely myocardin-independent manner. SWI/SNF-mediated chromatin remodeling thus regulates the phenotype of smooth muscle by affecting expression of protein-coding genes and microRNAs.
Debt-equity choice under asymmetric information and taxes

Abstract Under asymmetric information regarding the quality of investment opportunities and a tax advantage to debt, it is demonstrated that a separating equilibrium in which higher-quality firms issue equity and lower-quality firms issue debt may exist. Thus, the ‘pecking order’ theory may break down when debt financing enjoys a tax advantage.
Evaluation of Fiber Tracking from Subsampled q-Space Data in Diffusion Spectrum Imaging

Diffusion spectrum imaging (DSI) is capable of resolving crossing and touching fiber bundles in a given voxel. Acquisition of DSI data involves sampling large number of points in the q-space which significantly increases scan times. The scan times can be reduced by exploiting the symmetry of the q-space. In this study the fiber pathways for five (fornix, cingulum, superior longitudinal fasciculus, corticospinal tract, and crossing fibers in the centrum semiovale region) fiber bundles derived using three subsampled data sets of different sizes derived from the 257 samples in the q-space are compared. The coefficient of variation of the ratio of the number of fiber pathways for each subsample data set to the original data points, averaged over all the 10 subjects, was used for quantitatively investigating the effect of subsampling on the tractography. The effect of threshold angles on tractography is also investigated. The effect of subsampling on the orientation distribution function (ODF) was quantitatively evaluated using both scalar and vector measures derived from the ODF. A streamline tractography method that improves the curvature problem and reduces the local truncation error to further improve the mapping of fiber pathways is adapted. Analysis of the fiber pathways in ten normal subjects, based on qualitative and quantitative methods, shows that the 129 and 198 q-space points provide very similar result with angle of threshold between 41° and 45°. Based on the scan time advantage, 129 subsampled points appear to be adequate for tractography.
Subband coding methods for seismic data compression

Summary form only given. A typical seismic analysis scenario involves collection of data by an array of seismometers, transmission over a channel offering limited data rate, and storage of data for analysis. Seismic data analysis is performed for monitoring earthquakes and for planetary exploration as in the planned study of seismic events on Mars. Seismic data compression systems are required to cope with the transmission of vast amounts of data over constrained channels and must be able to accurately reproduce occasional high energy seismic events. We propose a compression algorithm that includes three stages: a decorrelation stage based on subband coding, a quantization stage that introduces a controlled amount of distortion to allow for high compression ratios, and a lossless entropy coding stage based on a simple but efficient block-adaptive arithmetic coding method. Adaptivity to the non-stationary behavior of the waveform is achieved by partitioning the data into blocks which are encoded separately. The compression ratio of the proposed scheme can be set to meet prescribed fidelity requirements, i.e. the waveform can be reproduced with sufficient fidelity for accurate interpretation and analysis. The distortions incurred by this compression scheme are currently being evaluated by several seismologists. Encoding is done with high efficiency due to the low overhead required to specify the parameters of the arithmetic encoder. Rate-distortion performance results on seismic waveforms are presented for various filter banks and numbers of levels of decomposition.
Importance of the C-1 substituent in classical cannabinoids to CB2 receptor selectivity: Synthesis and characterization of a series of O,2-propano-Delta(8)-tetrahydrocannabinol analogs

The separation of the mood-altering effects of cannabinoids from their therapeutic effects has been long sought. Results reported here for a series of C-9 analogs of the cyclic ether O,2-propano-delta 8-tetrahydrocannabinol (O,2-propano-delta 8-THC) point to the C-1 position in classical cannabinoids as a position for which CB2 subtype selectivity occurs within the cannabinoid receptors. O,2-Propano-11-delta 8-THC, O,2-propano delta 9,11-THC, O,2-propano-9-oxo-11-nor-hexahydrocannabinol (O,2-propano-9-oxo-11-nor-HHC), and O,2-propano-9 alpha- and O,2-propano-9 beta-OH-11-nor-HHC were synthesized and evaluated in radioligand displacement assays for affinity at the CB1 and CB2 receptors and in the mouse vas deferens in vitro assay and the mouse tetrad in vivo assay for cannabinoid activity. Evaluation of binding affinity at the CB1 and CB2 receptors revealed that each compound possesses a modest increased affinity for the CB2 receptor. Analogs which contained an oxygen attached to C-9 (i.e., oxo and hydroxy derivatives) showed the highest affinity and selectivity for CB2 (for O,2-propano-9-oxo-11-nor-HHC, Ki(CB1) = 90 nM, Ki(CB2) = 23 nM, selectivity ratio 3.9; for O,2-propano-9 beta-OH-11-nor-HHC, Ki(CB1) = 26 nM, Ki(CB2) = 5.8 nM, selectivity ratio 4.5). Each compound was found to produce a dose-dependent inhibition of electrically-evoked contractions of the mouse isolated vas deferens when administered at submicromolar concentrations. This inhibition could readily be prevented by the selective CB1 cannabinoid receptor antagonist SR-141716A. The analogs exhibited unique in vivo profiles with O,2-propano-delta 9,11-THC exhibiting antinociception with reduced activity in three other in vivo measures and O,2-propano-9 beta-OH-HHC exhibiting lack of dose responsiveness in all measures. The CB2 selectivities in the O,2-propano analogs may be due to differences in solvation/desolvation that occur when the ligands enter the CB1 vs CB2 binding site. Alternatively, the CB2 selectivities may be a results of an amino acid change from a hydrogen bond-accepting residue in CB1 to a hydrogen bond-donating residue in CB2.
A radioimmunoassay for dehydroepiandrosterone sulfate in the circulation of rhesus monkeys

Abstract A radioimmunoassay for dehydroepiandrosterone sulfate (DHAS) was established and validated for use in the rhesus monkey. The validation demonstrated the co-migration of immunoreactive material with tritiated dehydroepiandrosterone after hydrolysis and indicated the absence of other interfering steroids in the measurement. The application of this assay to perinatal samples verified that there are microgram quantities of DHAS present in the circulation. The measurement of circulating concentrations of DHAS in male and female rhesus monkeys at different stages of development demonstrated the absence of increases associated with puberty in this macaque species. Concentrations of DHAS were similar in adult males and females, but were elevated in pregnant females (p
Progress towards an effective syphilis vaccine: the past, present and future

Syphilis is a disease caused by infection with the spirochetal pathogen Treponema pallidum subspp. pallidum. Despite intensive efforts, the unusual biology of T. pallidum has hindered progress towards the development of a vaccine to prevent infection. This review describes previous endeavors to develop a syphilis vaccine, outlines the key issues in the field and proposes new directions in the design of a T. pallidum vaccine. Following a brief overview of the disease symptoms, epidemiology, diagnosis and treatment, a case is put forward for the benefit of pursuing a syphilis vaccine. Relevant material concerning immunity to T. pallidum infection is summarized and evaluated, and pilot experiments describing the use of whole-cell bacterin vaccines and similar preparations are included. A detailed section concerning subunit vaccines is provided, incorporating discussions pertaining to relevant antigen selection, the identification of putative T. pallidum surface-exposed outer membrane proteins, factors hindering previous attempts to vaccinate with recombinant outer membrane proteins, problems and pitfalls of syphilis outer membrane protein-based vaccines, anti-attachment vaccines and the potential use of nonprotein subunit preparations as vaccinogens. Subsequently, critical aspects concerning vaccine antigen preparation and delivery are noted, including protein conformation, synergy, post-translational modifications, live attenuated organisms as vaccine vectors, prime-boost methodologies, adjuvant selection and immunization routes. Finally, animal models are discussed with particular reference to immunoprotection studies. A more thorough understanding of immunity to syphilis, a comprehensive assessment of the immunoprotective capacity of the putative surface-accessible antigens of T. pallidum and utilization of the latest advances in vaccine science should set the scene for future development of a syphilis vaccine.
Ejection fraction determination without planimetry by two-dimensional echocardiography: A new method

A new method for determining ejection fraction by two-dimensional echocardiography was assessed in 60 patients undergoing angiography. In method A, the left ventricular minor axis was measured at the midventricular cavity level in end-systole and end-diastole using the apical four chamber view in the 60 patients. The left ventricular major axis was also measured from the left ventricular apex to the base of the mitral valve at end-systole and end-diastole. The ejection fraction was determined using a modified cylinder-ellipse algorithm. In method B, measurements of the left ventricular minor axis were made in 40 consecutive patients, at the upper, middle and lower thirds of the left ventricular cavity at end-systole and end-diastole of the same cardiac cycle and left ventricular major axis was measured as in method A. With use of the same algorithm, three regional ejection fractions were determined and averaged to yield the total ejection fraction. The two echocardiographic methods were compared with single plane cineangiography in all patients and with gated nuclear scanning in 14 patients. Reproducibility was assessed by interobserver comparison. Correlation was determined in all patients and then separately for those with echocardiographic wall motion abnormalities. The correlation coefficient for all patients was 0.79 (probability [p] Unlike a previous study, this method directly measures fractional shortening of left ventricular major axis and ejection fraction values are not arbitrarily modified by type of wall motion abnormality. With this method, accurate measurement of ejection fraction can be made by two-dimensional echocardiography without planimetry. In the absence of echocardiographic wall motion abnormalities, a very simple method A suffices. If wall motion abnormalities are present, the regional ejection fraction method B provides excellent results.
Integrin-linked Kinase (ILK) Binding to Paxillin LD1 Motif Regulates ILK Localization to Focal Adhesions

Paxillin is a focal adhesion adapter protein involved in integrin signaling. Paxillin LD motifs bind several focal adhesion proteins including the focal adhesion kinase, vinculin, the Arf-GTPase-activating protein paxillin-kinase linker, and the newly identified actin-binding protein actopaxin. Microsequencing of peptides derived from a 50-kDa paxillin LD1 motif-binding protein revealed 100% identity with integrin-linked kinase (ILK)-1, a serine/threonine kinase that has been implicated in integrin, growth factor, and Wnt signaling pathways. Cloning of ILK from rat smooth muscle cells generated a cDNA that exhibited 99.6% identity at the amino acid level with human ILK-1. A monoclonal antibody raised against a region of the carboxyl terminus of ILK, which is identical in rat and human ILK-1 protein, recognized a 50-kDa protein in all cultured cells and tissues examined. Binding experiments showed that ILK binds directly to the paxillin LD1 motif in vitro. Co-immunoprecipitation from fibroblasts confirmed that the association between paxillin and ILK occurs in vivo in both adherent cells and cells in suspension. Immunofluorescence microscopy of fibroblasts demonstrated that endogenous ILK as well as transfected green fluorescent protein-ILK co-localizes with paxillin in focal adhesions. Analysis of the deduced amino acid sequence of ILK identified a paxillin-binding subdomain in the carboxyl terminus of ILK. In contrast to wild-type ILK, paxillin-binding subdomain mutants of ILK were unable to bind to the paxillin LD1 motif in vitro and failed to localize to focal adhesions. Thus, paxillin binding is necessary for efficient focal adhesion targeting of ILK and may therefore impact the role of ILK in integrin-mediated signal transduction events.
Depth perception in the dark-reared rat as a function of time in the dark

Dark-reared hooded rats were tested for depth perception on the visual cliff. Ss were given an equal density condition to equate retinal angle presented during testing. Ss were kept in the dark from birth and tested after 40–170 days without visual stimulation. Dark-reared Ss 90 days of age, and perhaps to 125 days of age, discriminated depth. No group kept in the dark 140 days of longer discriminated depth.