cssi/SciSciGPT-SciSciNet huggingface dataset:
Low-Rank Registration Based Manifolds for Convection-Dominated PDEs

We develop an auto-encoder-type nonlinear dimensionality reduction algorithm to enable the construction of reduced order models of systems governed by convection-dominated nonlinear partial differential equations (PDEs), i.e. snapshots of solutions with large Kolmogorov n-width. Although several existing nonlinear manifold learning methods, such as LLE, ISOMAP, MDS, etc., appear as compelling candidates to reduce the dimensionality of such data, most are not applicable to reduced order modeling of PDEs, because: (i) they typically lack a straightforward mapping from the latent space to the high-dimensional physical space, and (ii) the identified latent variables are often difficult to interpret. In our proposed method, these limitations are overcome by training a low-rank diffeomorphic spatio-temporal grid that registers the output sequence of the PDEs on a non-uniform parameter/time-varying grid, such that the Kolmogorov n-width of the mapped data on the learned grid is minimized. We demonstrate the efficacy and interpretability of our proposed approach on several challenging manufactured computer vision-inspired tasks and physical systems.
The 50th anniversary of the Konopka and Benzer 1971 paper in PNAS: "Clock Mutants of Drosophila melanogaster".

On September 1, 1971, unknowingly to most, the world changed for the fields of behavioral genetics and circadian clocks. Ronald Konopka, a graduate student with Seymour Benzer at Caltech, published a paper (1) that I would argue is the most important discovery ultimately leading to our current molecular understanding of the circadian clock in animals. In this classic paper, Ron and Seymour reported the isolation of three single-gene mutants in Drosophila that dramatically altered circadian rhythms in pupal eclosion and locomotor activity. One mutant exhibited no rhythmicity, another had a short 19-h period, and a third had a long 28-h period. Remarkably, all three mutants mapped to the same locus on the X chromosome. They named this gene period . Seymour Benzer had recently joined the faculty at Caltech in 1967, after two previously successful careers in physics and molecular biology, and spurred on by Max Delbruck to do something more interesting, launched his third career in behavioral biology (2⇓⇓–5). Having done a sabbatical at Caltech with Roger Sperry, Seymour interacted with Ed Lewis, a giant in Drosophila genetics who trained with Alfred Sturtevant (descendent of Thomas Hunt Morgan) (6). Seymour chose Drosophila as a model system because its nervous system was intermediate in complexity “between a single neuron and the human brain” yet exhibited complex behavior and was amenable to genetic analysis (7). That same year, Seymour published his first paper (8) using mutagenesis and countercurrent technology to isolate phototaxis mutants in Drosophila . The opening sentence of this paper reads, “Complex as it is, much of the vast network of cellular functions has been successfully dissected, on a microscopic scale, by the use … [↵][1]1Email: joseph.takahashi{at}utsouthwestern.edu. [1]: #xref-corresp-1-1
Effect of Structural Changes Induced by Deletion of 54FLRAPSWF61 Sequence in αB-crystallin on Chaperone Function and Anti-Apoptotic Activity

Previously, we showed that the removal of the 54–61 residues from αB-crystallin (αBΔ54–61) results in a fifty percent reduction in the oligomeric mass and a ten-fold increase in chaperone-like activity. In this study, we investigated the oligomeric organization changes in the deletion mutant contributing to the increased chaperone activity and evaluated the cytoprotection properties of the mutant protein using ARPE-19 cells. Trypsin digestion studies revealed that additional tryptic cleavage sites become susceptible in the deletion mutant than in the wild-type protein, suggesting a different subunit organization in the oligomer of the mutant protein. Static and dynamic light scattering analyses of chaperone–substrate complexes showed that the deletion mutant has more significant interaction with the substrates than wild-type protein, resulting in increased binding of the unfolding proteins. Cytotoxicity studies carried out with ARPE-19 cells showed an enhancement in anti-apoptotic activity in αBΔ54–61 as compared with the wild-type protein. The improved anti-apoptotic activity of the mutant is also supported by reduced caspase activation and normalization of the apoptotic cascade components level in cells treated with the deletion mutant. Our study suggests that altered oligomeric assembly with increased substrate affinity could be the basis for the enhanced chaperone function of the αBΔ54–61 protein.
Untold stories: Emergency medicine residents' experiences caring for diverse patient populations.

Objectives The Accreditation Council for Graduate Medical Education expects specialties to teach and assess proficiency in culturally competent care. However, little guidance has emerged to achieve these goals. Clinical training within socioeconomically disparate settings may provide an experiential learning opportunity. We sought to qualitatively explore resident experiences working in the generic clinical learning environments (i.e., exposure to socioeconomically diverse patients across different training sites) and how it shapes cultural competency-related skill development. Methods Residents were recruited from emergency medicine (EM) programs. We used purposeful sampling across all postgraduate years and elicited experiences related to working at the different sites related to cultural identity, frustrating patient encounters, vulnerable populations, and development of health disparities/social determinants of health knowledge. Individual structured interviews were conducted via phone between May and December 2016. Interviews were audiotaped, transcribed, anonymized, and analyzed using systematic and iterative coding methods. Results Twenty-four interviews revealed three main themes. EM residents' experiences caring for patients across sites shaped their understanding of: (1) potential patient attributes that affected the clinical encounter, (2) difficulties in building rapport had adverse effect on the clinical evaluation, and (3) residency program and training experiences shaped their clinical preparedness and willingness to work in underserved areas. Conclusion Assessing the impact disparate clinical setting exposures have on trainees' preparedness to care for socioeconomically diverse patients can provide valuable insight for medical educators into barriers and facilitators to delivering optimal learning and patient care. Participants provided a breadth of stories illuminating their real-world consciousness and competency with meeting the needs of diverse populations and their access to varied educational outlets to grapple with the disparities they observed. More research is needed to uncover effective strategies to help residents thrive and feel more prepared to care for diverse populations.
WebSeq: A Genomic Data Analytics Platform for Monogenic Disease Discovery

Whole exome sequencing (WES) is commonly used to study monogenic diseases. The application of this sequencing technology has gained in popularity amongst clinicians and researchers as WES pricing has declined. The accumulation of WES data creates a need for a robust, flexible, scalable and easy-to-use analytics platform to allow researchers to gain biological insight from this genomic data. We present WebSeq, a self-contained server and web interface to facilitate intuitive analysis of WES data. WebSeq provides access to sophisticated tools and pipelines through a user-friendly and modern web interface. WebSeq has modules that support i) FASTQ to VCF conversion, ii) VCF to ANNOVAR CSV conversion, iii) family-based analyses for Mendelian disease gene discovery, iv) cohort-wide gene enrichment analyses, (v) an automated IGV browser, and (vi) a 9virtual gene panel9 analysis module. WebSeq Pro, our expanded pipeline, also supports SNP genotype analyses such as ancestry inference and kinship testing. WebSeq Lite, our minimal pipeline, supports family-based analyses, cohort-wide gene enrichment analyses, and a virtual gene panel along with the IGV browser module. We anticipate that the rigorous use of our web application will allow researchers to expedite discoveries from human genomic data. WebSeq Lite, WebSeq, and WebSeq Pro are fully containerized using Docker, run on all major operating systems, and are freely available for personal, academic, and non-profit use at http://bitly.ws/g6cn .
Cointegration and Priority Relationships Between Energy Stocks and Oil Prices

This study investigates the cointegration and priority relationships between large-cap energy stocks and oil price changes over the last decade. The results reveal that energy stock prices have a long run linear relationship with oil price fluctuations. Asset prices are affected by the oil price deviations from the long run equilibrium as well as the short run dynamics. Moreover, some particular energy stocks have Granger causal impacts on oil market as well. The existence of this bivariate long run cointegration implies that employing portfolio diversification between these two markets would be efficient.
Possible Mechanisms of Action of the Anticarcinogenic Protease Inhibitors

Protease inhibitors have been shown to possess anticarcinogenic properties. Two synthetic protease inhibitors, tosyl phenylethyl chloro-methyl ketone (TPCK) and tosylarginine methylester (a competitive trypsin substrate), have been demonstrated to block the formation of skin tumors promoted with TPA in mice (1). These studies were repeated using the actinomycete-derived protease inhibitor leupeptin (2), thus establishing an in vivo basis for the involvement of proteases in the mechanism of carcinogenesis.
Sulfonylurea binding to adipocyte membranes and potentiation of insulin-stimulated hexose transport.

Abstract We have previously shown that the sulfonylureas increase insulin-stimulated glucose transport in adipocytes mainly by enhancing the insulin-induced recruitment of glucose transporter from its intracellular storage pool to the plasma membrane (Jacobs, D. B., and Jung, C. Y. (1985) J. Biol. Chem. 260, 2593-2596). In order to determine if this sulfonylurea effect is mediated by a specific membrane-associated sulfonylurea-binding protein, in the present report we measured exact dose dependence of the transport enhancement activities of different sulfonylureas in adipocytes in primary culture and equilibrium binding affinities of these agents to various adipocyte membrane fractions. Glycuride was found to increase the insulin-stimulated, 3-O-methyl-D-glucose equilibrium exchange in cultured rat adipocytes by up to 60% with little effect in the absence of insulin. The effect developed gradually reaching the maximum level at 24 h of incubation. The effect was concentration dependent showing a simple, one-to-one stoichiometry and an apparent activation constant (Ka) of approximately 1 microM. Glypizide, tolazamide, and tolbutamide also enhanced the insulin-stimulated hexose transport by up to 60%, but with Ka of approximately 2, 11, and 25 microM, respectively. HB-699 and ciglitazone, non-sulfonylureas, were without effect under the same condition. In equilibrium binding experiments, [3H]glyburide was found to bind to adipocyte membranes at two or more protein-specific, saturable sites, with similar apparent dissociation constants (KD) ranging 1-3 microM. These protein-specific glyburide bindings were displaced not only by tolazamide and tolbutamide, but also by ciglitazone and HB-699, with indicated KD of 11-16, 80-85, 20-25, and 85-95 microM, respectively. However, with the plasma membrane fraction, the displacements by ciglitazone and HB-699 were partial and did not exceed 56-61% at maximum. Based on these findings, we propose that there is a sulfonylurea-specific-binding protein in the plasma membrane of adipocytes, and that this sulfonylurea-binding protein may play a key role in the enhancement of insulin-stimulated hexose transport by sulfonylureas, probably via potentiation of the insulin-induced recruitment of glucose transporter.
Rapidly Installed Fluid Transfer System (RIFTS)

Abstract : Fossil fuels will continue to be the primary propulsion fuel for military aircraft, vehicles, and ground equipment for the foreseeable future. Water is the critical fuel to sustain the ultimate weapon, our soldiers. Distributing large quantities of bulk fuel and water required on the battlefield in the 21st century will require rapid deployment, installation, and recovery capabilities not inherent in existing petroleum and water distribution equipment. The Rapidly Installed Fluid Transfer System (RIFTS) will be designed to minimize strategic transport assets to deliver it to the theater of operation, will require fewer assets to deploy, will be easily recovered for redeployment. and will have an expected minimum service life of 15-25 years.
Party Campaign Contributions Come with a Support Network

Objectives Contributions to candidates from the parties’ congressional campaign committees are thought to have a “multiplier effect” in terms of generating contributions from political action committees. Method Using structural equation modeling and timed direct contribution data from the 1992 to 2012 general election cycles, I uncover a complex system of relationships within each party network. Results After controlling for the competitiveness of the race, I find party contributions to challengers and open-seat contestants early in the election cycle positively and significantly predict political action committee contributions to those candidates in the period after Labor Day, both in the era preceding the Bipartisan Campaign Finance Reform Act and the era after reform; however, the strength of the relationship declines in the postreform era and differences between the party networks also arise. Conclusions I attribute these developments to changes in campaign finance law that created new hurdles for parties and increased the influence of interest groups.
Analysis of Burst Observations by GLAST’s LAT Detector

Analyzing data from GLAST’s Large Area Telescope (LAT) will require sophisticated techniques. The PSF and effective area are functions of both photon energy and the position in the field‐of‐view. During most of the mission the observatory will survey the sky continuously, and thus, the LAT will detect each count from a source at a different detector orientation; each count requires its own response function! The likelihood as a function of celestial position and photon energy will be the foundation of the standard analysis techniques. However, the 20 MeV–300 GeV emission at the time of the ∼ 100 keV burst emission (timescale of ∼ 10 s) can be isolated and analyzed because essentially no non‐burst counts are expected within a PSF radius of the burst location during the burst. Both binned and unbinned (in energy) spectral fitting will be possible. Longer timescale afterglow emission will require the likelihood analysis that will be used for persistent sources.
Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1.

CD4 + FoxP3 + regulatory T cells (T reg ) play a critical role in maintaining self-tolerance and inhibiting autoimmune disease. Despite being a major focus of modern immunological investigation, many aspects of T reg biology remain unknown. In a screen for novel candidate genes involved in human T reg function, we detected the expression of an autoimmune susceptibility gene, FcRL3, in T reg but not in conventional CD4 + T cells. FcRL3 is an orphan receptor of unknown function with structural homology to classical Fc receptors. Numerous genetic studies have demonstrated a link between a single nucleotide polymorphism in the FCRL3 promoter and both overexpression of FcRL3 and autoimmune diseases such as rheumatoid arthritis. Given the critical role of T reg in suppressing autoimmunity, we sought to ascertain how expression of FcRL3 relates to the phenotype, differentiation, and function of T reg . We show in this study that FcRL3 is expressed on a population of thymically derived T reg that exhibits a memory phenotype and high levels of programmed cell death-1. Purified FcRL3 + T reg are less responsive to antigenic stimulation in the presence of IL-2 than their FcRL3 − counterparts, despite intact proximal and distal IL-2 signaling as determined by phosphorylation of Stat-5 and upregulation of Bcl2. In vitro suppression assays demonstrated that FcRL3 + T reg have reduced capacity to suppress the proliferation of effector T cells. These data suggest that FcRL3 expression is associated with T reg dysfunction that may, in turn, contribute to the loss of self-tolerance and the development of autoimmunity.
Prototype design and experimental study on locust air-posture righting

Locust has the capacity to maintain a righting posture and glide through attitude adjustment after leaping. A prototype inspired by the dynamic mechanism of attitude adjustment of locusts was developed. The prototype consists of a pair of wings driven by a four-bar mechanism, and a 2 Degree of Freedom (DOF) tail to imitate the movement of the locust abdomen. The power source, microcontroller, wireless data transmission module, and attitude sensors are contained in the fuselage. Experiments imitating the flight of locust were conducted to determine the mechanism of locust Subsequent Attitude Adjustment (SAA). The tethered prototype was driven by the movement of the tail and the flapping of the wings. Results show that the pitch and yaw of the tail, and the asymmetric action of the flapping wings significantly influence the posture of the prototype. These findings suggest that both the wiggling abdomen and flapping wings contribute to the locust SAA in the air. This research lays the groundwork and technical support for the probable design and development of practical jumping robots with attitude adjustment function.
A Mobius strip of scientific imagination. How deep does the relationship between science fiction and science go

From H.G. Wells to Star Trek, science fiction and science have had a long and fruitful relationship. But does science drive the imagination of authors, or do authors drive the imaginations of scientists?
Measurement of plasma dihydrotestosterone by competitive protein-binding analysis

Abstract A competitive protein binding method for the measurement of dihydrotestosterone (DHT) concentration in plasma is described. The mean recovery throughout the procedure was 75 ± 11%. Water blanks (10 ml) ranged from 0 to 0.2 ng per sample. The precision and accuracy were good. The specificity was checked by preparation of two further derivatives of DHT. Mean plasma values of DHT for normal adult women and men were respectively 21.7 ± 4.3 (S.D.) and 50.1 ± 14.4 (S.D.) ng/100 ml. Simultaneously by taking a smaller aliquot following the paper chromatography, plasma testosterone (T) concentrations could be measured by competitive protein binding.
Serotonin and motor activity

The activity of brain serotonergic neurons in both the pontine-mesencephalic and medullary groups is positively correlated with the level of behavioral arousal and/or the behavioral state. This, in turn, appears to be related to the level of tonic motor activity, especially as manifested in antigravity muscles and other muscle groups associated with gross motor activity. In addition, a subset of serotonergic neurons displays a further increase in activity in association with repetitive, central pattern generator mediated responses. Accumulating evidence indicates that this relation to motor activity is related both to the co-activation of the sympathetic nervous system and to the modulation of afferent inputs.
Inclusion of Moloney murine leukemia virus elements upstream of the transgene cassette in an E1-deleted adenovirus leads to an unusual genomic integration in epithelial cells.

Abstract Classically, the 5′ and 3′ long terminal repeats (LTRs) are considered necessary but not sufficient for retroviral integration. Recently, we reported that inclusion of these and additional elements from Moloney murine leukemia virus (MoMLV) facilitated transgene integration, without retroviral integrase, when placed in an adenoviral context (AdLTR-luc vector) (Nat. Biotech. 18 (2000), 176; Biochem. Biophys. Res. Commun. 300 (2003), 115). To help understand this nonhomologous DNA recombination event, we constructed another vector, AdELP-luc, with 2.7 kb of MoMLV elements identically placed into an E1-deleted adenovirus type 5 backbone upstream of a luciferase cDNA reporter gene. Unlike AdLTR-luc, no MoMLV elements were placed downstream of the expression cassette. AdELP-luc readily infected epithelial cells in vitro. Southern hybridizations with DNA from cloned cells showed that disruption of the MoMLV sequences occurred. One cell clone, grown in vitro without any special selection medium for 9 months, exhibited stable vector integration and luciferase activity. Importantly, both Southern hybridization and FISH analyses showed that in addition to the MoMLV elements and expression cassette, substantial adenoviral sequence downstream of the luciferase cDNA was genomically integrated. These results suggest that the 2.7 kb of MoMLV sequence included in AdELP-luc have cis -acting functions and mediates an unusual integration event.
Research on Characteristics of Horizontal Atmospheric Diffusion Coefficient Based on BP Neural Network

In order to obtain the actual characteristics of horizontal atmospheric diffusion direction, based on Gauss plume model and the measured data, we use BP neural network to fit the characteristic curve of the diffusion coefficient. We establish a BP neural network, and then we train the network and simulate the diffusion coefficient. According to the simulation results, we compare the characteristic curve with the curve based on the least square method. And the results show that the characteristic curve based on BP neural network has better fitting accuracy. Hence, using the trained neural network to predict the diffusion coefficient has certain theory meaning and actual application value.
Tactile letter recognition: Pattern duration and modes of pattern generation

Measurements were made of the ability of subjects to identify vibrotactile patterns presented to their fingertips. The patterns were letters of the alphabet generated on the tactile display of the Optacon. Five different modes of pattern generation were examined. Two of the modes, static and scan, involved full-field presentations of the letters. In the remaining three modes, patterns were generated by presenting parts of the letters sequentially. In one mode, the letters were exposed by a slit passing across them. In the other two modes, the patterns were generated as though the letter were being drawn on the skin. Performance in all five modes was examined as a function of pattern duration, with durations ranging from 4 to 1,000 msec. Increasing duration, up to 400 msec, resulted in generally improved performance, although the functions relating performance and duration differed according to the mode of presentation. Contrary to previous results, the static mode produced the best overall performance level. Some possible reasons for the disagreement between the present results and previous results and some models of cutaneous pattern recognition are discussed.
Chirping effect on electrooptic modulator SBN single-crystal fiber in microwave cavity

A ferroelectric single crystal fiber placed inside a microwave cavity is designed to perform pulse uptuning, downtuning, or reshaping by utilizing chirping effects on optical pulses traversing through it. For electrooptic modulator devices ferroelectric crystal fibers are of significant interest due to their high electrooptic coefficients and near-circular cross-sectional waveguide configuration. Single crystal fibers of strontium barium niobate grown by the laser heated pedestal growth method are shown to have high sensitivity to microwave electromagnetic field. Quantitative exploration for the influence of chirping on the performance of this modulator in a microwave cavity waveguide is carried out and reported.
Moving mountains to get IM&T in the orientation mix

With Savannah College of Art and Design's growing dependency on technology, we have identified the need to train our incoming faculty, staff, and students to use the technology that is necessary to thrive in our academic environment. Once this need was identified, we then had to find ways to integrate technology training into orientation. So far, our efforts with faculty and staff have been very successful, and we are still working on the best approach to reach all incoming students.To reach faculty and staff, we met with Human Resources and Faculty Development and agreed that all full-time faculty and staff would be required to attend a technology orientation in order to receive their network/email account access. Staff technology orientation is a 2½-hour session held on the second day of orientation. Faculty members attend a 3-hour technology session on the first day of their orientation with the school.The most challenging step of this process to date has been the inclusion of technology training into student orientation. We have tried several different methods to communicate the technology message that we have for students and are continuously revising this process. We are limited on time, space, and personnel to reach all the incoming students especially during the large influx of fall quarter.This paper will examine the steps that were taken to integrate technology into faculty and staff orientations and examine the on-going processes for addressing our students' training needs.
Comparison of dynamical aspects of nonadiabatic electron, proton, and proton-coupled electron transfer reactions

Abstract The dynamical aspects of a model proton-coupled electron transfer (PCET) reaction in solution are analyzed with molecular dynamics simulations. The rate for nonadiabatic PCET is expressed in terms of a time-dependent probability flux correlation function. The impact of the proton donor–acceptor and solvent dynamics on the probability flux is examined. The dynamical behavior of the probability flux correlation function is dominated by a solvent damping term that depends on the energy gap correlation function. The proton donor–acceptor motion does not impact the dynamical behavior of the probability flux correlation function but does influence the magnitude of the rate. The approximations previously invoked for the calculation of PCET rates are tested. The effects of solvent damping on the proton donor–acceptor vibrational motion are found to be negligible, and the short-time solvent approximation, in which only equilibrium fluctuations of the solvent are considered, is determined to be valid for these types of reactions. The analysis of PCET reactions is compared to previous analyses of single electron and proton transfer reactions. The dynamical behavior is qualitatively similar for all three types of reactions, but the time scale of the decay of the probability flux correlation function is significantly longer for single proton transfer than for PCET and single electron transfer due to a smaller solvent reorganization energy for proton transfer.
Carbon-13 NMR relaxation studies of pre-melt structural dynamics in [4-13C-uracil] labeled E. coli transfer RNAIVal.

Abstract We report 67.8 MHz carbon-13 spin-lattice relaxation studies on [4-13C-uracil] labeled tRNAIVal purified from E. coli SO-187. Following 13C-enriched C4 carbonyl resonances from modified and unsubstituted uridines scattered throughout the polymer backbone enables us to determine dynamical features in both loop and helical stem regions. The experimental results have been analyzed in terms of a model of isotropic overall molecular reorientation. "Anomalous" residues for which the experimental data cannot be accounted for in terms of the model provide an assessment of local and regional properties. Thus, "native" tRNAIVal under physiological conditions of magnesium (10 mM) and temperature (20 degrees - 40 degrees C), exhibits the following characteristics: 1) uridines held rigidly in helical stems and tertiary interactions display correlation times for rotational reorientation of 15-20 nsecs, typical for overall tRNA motion; 2) uridines in loops such as the wobble residue uridine-5-oxyacetic acid (V34) are quite accessible to solvent; moreover V34 and another loop residue, D17, exhibit local mobility; 3) the tertiary interactions involving 4-thio uridine (s4U8) and A14 and ribothymidine (rT54) and A58 are weakened as temperature increases.
Elastic deformation and the coefficient of friction

Abstract A geometrical model for the area of contact between surfaces has been suggested by Archard . Calculations based upon this model show that the calculated coefficient of friction does not agree with experimental results. The reason for this disagreement is that within the model itself there are no limitations on possible values of the geome tric parameters which describe the surfaces in contact. The lack of such limitations make it impossible to choose on the basis of this model among the wide range of values for the coefficient of friction generated by different choices of value for the geometric parameters.
Exercise conditioning and heart rate variability: evidence of a threshold effect.

Background: A protective effect of exercise in preventing sudden cardiac death is supported by studies in healthy populations as well as in patients with cardiac disease. The mechanisms involved in this protective effect are unknown. Hypothesis: We hypothesized that exercise conditioning would beneficially alter autonomic nervous system tone, measured by heart rate variability. Methods: We prospectively studied 20 cardiac patients enrolled in a Phase 2 12-week cardiac rehabilitation program following a recent cardiac event. The patients underwent 24 h Holter monitoring at program entry and 12 weeks later. Heart rate variability analysis was assessed for both time domain and spectral analysis. Results: The group demonstrated a modest mean conditioning effect, indicated by an average reduction in resting heart rate from 81 ± 16 to 75 ± 12 beats/min (p = 0.03), and an increase in training METS from 2.1 ± 0.4 to 3.3 ± 1.1 (p 1.5 training METS demonstrated significant increases in SDNN, SDANN index, SDNN index, pNN50, total power, and high-frequency power (all p < 0.05) (see text for explanation of abbreviations). Conclusions: Exercise conditioning improves heart rate variability in cardiac patients, particularly in patients who achieve a threshold of > 1.5 training METS increase over a 12-week period. These study results are supportive of the concept that exercise training lowers the risk of sudden cardiac death via increased vagal tone, which likely beneficially alters ventricular fibrillatory and ischemic thresholds.
The Sympathetic Nervous System in Obesity Hypertension

Abundant evidence supports a role of the sympathetic nervous system in the pathogenesis of obesity-related hypertension. However, the nature and temporal progression of mechanisms underlying this sympathetically mediated hypertension are incompletely understood. Recent technological advances allowing direct recordings of renal sympathetic nerve activity (RSNA) in conscious animals, together with direct suppression of RSNA by renal denervation and reflex-mediated global sympathetic inhibition in experimental animals and human subjects have been especially valuable in elucidating these mechanisms. These studies strongly support the concept that increased RSNA is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretory function, causing obesity hypertension. Potential determinants of renal sympathoexcitation and the differential mechanisms mediating the effects of renal-specific versus reflex-mediated, global sympathetic inhibition on renal hemodynamics and cardiac autonomic function are discussed. These differential mechanisms may impact the efficacy of current device-based approaches for hypertension therapy.
NEXIS Cathode Measurements at the Species Level

A series of particle-based measurements are in progress on a laboratory cathode previously operated in a NEXIS ion engine. A cylindrical anode, without extraction grids, surrounds the cathode. Measurements were performed using a retarding potential analyzer and quadrupole mass spectrometer to obtain information about plume ions. A laser absorption spectrometer is being prepared to measure the internal density of critical species, with atomic barium the initial target. Details of the spectrometer and its sensitivity for detecting target species are discussed.
Altered forebrain neurotransmitter responses to immobilization stress following 3,4-methylenedioxymethamphetamine

(+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is an increasingly popular drug of abuse that acts as a neurotoxin to forebrain serotonin neurons. The neurochemical effects of the serotonin depletion following high doses of MDMA were investigated in response to acute immobilization stress. Male rats were treated with a neurotoxic dosing regimen of MDMA (10 mg/kg, i.p. every 2 h for four injections) or equivalent doses of saline. Seven days after treatment, in vivo microdialysis was used to assess extracellular dopamine and serotonin in the dorsal hippocampus and prefrontal cortex during 1 h of immobilization stress. In saline treated control rats, serotonin in the hippocampus and serotonin and dopamine in the prefrontal cortex were increased during immobilization stress. Rats pretreated with MDMA, however, showed blunted neurotransmitter responses in the hippocampus and the prefrontal cortex. In the drug pretreated rats, basal serotonin levels in the hippocampus, but not the prefrontal cortex, were lower compared to saline pretreated controls. Stress-induced increases in plasma corticosterone and body temperature were not affected by the pretreatment condition. From these studies we suggest that depletion of serotonin stores in terminal regions with the neurotoxin MDMA compromises the ability of the serotonergic neurons to activate central systems that respond to stressful stimuli. This altered responsiveness may have implications for long-term functional consequences of MDMA abuse as well as the interactions between the serotonergic system and stress.
Principles of Conventional Radiography and Fluoroscopy

Diagnostic radiology is an extremely valuable tool in the practice of veterinary medicine. Basic knowledge of primary exposure factors and their interrelationship are required to consistently produce quality radiographs. This article discusses basic radiation physics and radiation safety guidelines.
Parallel imaging of active pharmaceutical ingredients in some tablets and blends on Raman and near-infrared mapping and imaging platforms

Two types of tablets with the arbitrarily defined low and medium active pharmaceutical ingredient (API) loadings and a formulation blend with intentionally introduced large API agglomerate were inspected on Raman mapping and global imaging platforms as well as on the near-infrared (NIR) mapping platform. Only the API particles were identified and their images compared on the three systems. Several technical parameters were closely controlled such as spatial resolution in the images and acquisition times. The Raman mapping platform was found to be the most effective for determining the API in the low-loading formulation which was not analyzable by the other two methods. With regards to the medium loading of API in a tablet and the blend with an API agglomerate, the chemical images on all three platforms were found to be largely comparable with, in relative terms, the NIR mapping being the fastest and least complex to use.
The effect of central nervous system agents on rat-brain γ-aminobutyric acid level

Abstract γ-Aminobutyric acid has been implicated as a central nervous system neurohumoral depressant by a number of investigators. The hypothesis that brain excitability is inversely proportional to the γ-aminobutyric acid content was tested with compounds that were reported active by others and with a number of central nervous system stimulants and depressants. Of twelve compounds tested, e.g. , ethanol, hydroxylamine, pentylenetetrazol and phenobarbital, none produced dramatic changes in rat-brain γ-aminobutyric acid content. It was concluded that the presence of γ-aminobutyric acid in central nervous system tissue alone does not imply a physiological role a priori .
Pharmacokinetics of didanosine and drug resistance mutations in infants exposed to zidovudine during gestation or postnatally and treated with didanosine or zidovudine in the first three months of life.

Background: There are limited numbers of drugs that are available in formulations that are appropriate for neonates and few studies assessing resistance among infants born to human immunodeficiency virus (HIV)-infected women. Methods: Pharmacokinetics and tolerance of didanosine (ddl) were determined for infants ≤120 days of age. Infants received at least 24 hours of zidovudine (ZDV) treatment, followed by a single ddl dose and pharmacokinetic sampling. The target area under the concentration-time curve (AUC) was between 2.5 and 5.0 μM . hour. Toxicity and drug resistance mutations were assessed at baseline and follow-up times. Results: The initial ddl pharmacokinetic dosing of 50 mg/m 2 for infants >28 days of age achieved a median AUC 0- ∞ of 2.8 μM . hour. For infants ≤28 days of age, the target AUC was achieved after dose escalation from 25 mg/m 2 (median AUC 0- ∞, 1.4 μM . hour) to 50 mg/m 2 (median AUC 0- ∞, 5.40 μM . hour). At baseline, 25% of infected infants had drug resistance mutations (9 of 44 to ZDV and 2 of 44 to ddl). Resistance mutations were present for 29% of infants (5 of 17 infants) with in utero ZDV exposure and 25% (8 of 32 infants) with prior ZDV treatment. The most common ZDV mutation noted at baseline was the T215Y/F (n = 7) mutation; 2 of these infants also had the M41L mutation, which is associated with high level ZDV resistance. No prior exposure was noted for the 2 infants with ddI resistance, which indicates possible perinatal transmission of ddl-resistant virus to these infants. Conclusions: A dose of 50 mg/m 2 is the appropriate ddl dose for infants <120 days of age and is a safe treatment for newborns when used in combination with ZDV. Genotypic resistance occurs frequently among infected infants exposed to ZDV during gestation or postnatally, which suggests that resistance testing should be considered for infants with newly diagnosed HIV infection.
Mechanisms and Determinants of Ultralong Action Potential Duration and Slow Rate-Dependence in Cardiac Myocytes

In normal cardiac myocytes, the action potential duration (APD) is several hundred milliseconds. However, experimental studies showed that under certain conditions, APD could be excessively long (or ultralong), up to several seconds. Unlike the normal APD, the ultralong APD increases sensitively with pacing cycle length even when the pacing rate is very slow, exhibiting a sensitive slow rate-dependence. In addition, these long action potentials may or may not exhibit early afterdepolarizations (EADs). Although these phenomena are well known, the underlying mechanisms and ionic determinants remain incompletely understood. In this study, computer simulations were performed with a simplified action potential model. Modifications to the L-type calcium current (ICa,L) kinetics and the activation time constant of the delayed rectifier K current were used to investigate their effects on APD. We show that: 1) the ultralong APD and its sensitive slow rate-dependence are determined by the steady-state window and pedestal ICa,L currents and the activation speed and the recovery of the delayed rectifier K current; 2) whether an ultralong action potential exhibits EADs or not depends on the kinetics of ICa,L; 3) increasing inward currents elevates the plateau voltage, which in general prolongs APD, however, this can also shorten APD when the APD is already ultralong under certain conditions; and 4) APD alternans occurs at slow pacing rates due to the sensitive slow rate-dependence and the ionic determinants are different from the ones causing APD alternans at fast heart rates.
THE ARCHIVES OF THE MISSIONNAIRES DU SACRE-COEUR (M.S.C.) AT BAMANYA (ZAIRE)

Archival research in the Equateur region of Zaire is a frustrating and often unsuccessful endeavor. Colonial documentation on a specific locality is seldom located in a central repository and items have been scattered throughout the region. What records are found are usually highly disorganized and partially decomposed. In many cases, significant sources have been lost or destroyed. With this bleak prospective, it is not surprising that historical research in this area has been very limited. In contrast, a little known yet important source of historical and ethnographic material exists at the Missionnaires du Sacre-Coeur (M.S.C.) library at Bamanya, situated approximately ten kilometers from Mbandaka in the Equateur region. The library contains a wide range of both printed and archival material that has recently been organized and cataloged. Historians will find the archives to be of great interest and value, particularly for studies on the Nkundo-Mongo ethnic groups of the central forest region of Zaire.
Inhibition of HIV infectivity by human saliva

OBJECTIVE: Human saliva is known to decrease HIV infectivity in vitro. The purpose of this study was to extend these findings and to focus on the mechanism of action of these salivary factor(s). DESIGN: A number of viruses and several assay systems have been utilized to determine if the effect of submandibular saliva is directly on the virus, on the host cell, or on the virus-cell interaction. MATERIALS AND METHODS: Submandibular saliva from seronegative donors was incubated with HIV-1, other retroviruses, or unrelated viruses. Viral infectivity was monitored either by determining p24 antigen levels in peripheral blood mononuclear cells or Sup T1 cells, or using HeLa cells expressing CD4 and an HIV derived long terminal repeat linked to the β-galactosidase gene. RESULTS: The inhibition of viral infectivity by submandibular saliva is specific for HIV-1. While inhibition increases with time of incubation of saliva with virus, pre-treatment of cells with saliva does not inhibit HIV production, and saliva has only modest inhibitory effects when added to HIV-infected cells. CONCLUSIONS: It appears that the effect of submandibular saliva on decreasing the infectivity of HIV-1 is directly on the virus, rather than on the host cell.
The circular dichroic spectra of several sialic acid-containing polysaccharides isolated from neisseria meningitidis

The circular dichroic spectra of the acid and sodium salt forms of several sialic acid-containing homo- and hetero-polysaccharides have been measured. The spectra are shown to be influenced by the state of ionization of the carboxyl groups contained in the sialic acid, the location within the individual sialic acid residues of the inter-saccharide linkages, and changes in the configuration of hydroxyl groups remote to the carboxyl group of the sialic acid.
Direct connection between myelinosomes, endoplasmic reticulum and nuclear envelope in mouse hepatocytes grown with the amphiphilic drug, quinacrine

Abstract Mouse hepatocytes grown in 4 μM quinacrine had numerous myelinosomes which were directly connected to expanded cisternae of the rough endoplasmic reticulum (RER). The cisternae of the RER either subtended the electron transparent space of the myelinosome, expanded to form the outer membrane of the myelinosome or penetrated into it. Material of low electron density was frequently seen within the area where the cisternae penetrated into the electron transparent space of the myelinosome. Myelinosomes were also associated with the nuclear envelope in a pattern similar to that of the RER, Quinacrine appears to bind with the phospholipids of the membranes of the endoplasmic reticulum and nuclear envelope and this drug-lipid complex is then moved into myelinosomes effectively removing the drug from the cell.
Cytosolic calcium during contraction of isolated mammalian gastric muscle cells

During activation of visceral smooth muscle there is an increase in cytosolic-free calcium, but the source (intracellular calcium release or calcium influx), kinetics, and stoichiometry of this increase have not been determined. Here, the fluorescent indicator, quin2-acetoxymethyl ester, was used to measure directly cytosolic-free calcium during contraction of isolated stomach muscle cells induced by the two neuropeptides cholecystokinin-octapeptide and Met-enkephalin as well as acetylcholine. An increase in cytosolic-free calcium was seen that was (i) dependent on the concentration of contractile agonist, (ii) derived from intracellular sources (that is, not significantly affected by removal of ambient calcium or addition of a calcium channel blocker), and (iii) kinetically and stoichiometrically related to net calcium efflux and contraction. In contrast, the increase in cytosolic-free calcium induced by depolarizing concentrations of potassium was caused by influx of calcium through voltage-dependent calcium channels.
Reversal of diet-induced catabolism by infusion of recombinant insulin-like growth factor-I in humans.

Treatment of catabolic conditions with insulin-like growth factor I (IGF-I), the peptide that mediates some of the anabolic growth-promoting effects of GH, offers potential advantages of avoiding the hyperglycemia caused by treatment with GH. A state of moderate catabolism was produced in six normal, young adult volunteers by restricting their daily dietary intake to 20 kilocalories/kg/day. During the last 6 days of two 2-week diet-study periods, they received either IGF-I (12 micrograms/kg/h by i.v. infusion over 16 h) or GH (0.05 mg/kg/day by sc injection). IGF-I improved nitrogen balance from -236 +/- 45 mmol/day (+/- SE) during diet alone, to -65 +/- 40 mmol/day (P less than 0.001) during the last 4 days of IGF-I infusion. A similar effect was produced by GH. IGF-I infusion decreased fasting blood glucose from 4.94 +/- 0.91 mmol/L to 3.13 +/- 0.44 mmol/L (P less than 0.001), while GH raised blood glucose values (4.75 +/- 1.01 mmol/L on diet alone, to 5.48 +/- 1.00 during the period of GH treatment; P less than 0.05). Despite these differences in blood glucose, IGF-I infusions decreased serum insulin (74.9 +/- 26.8 pmol/L on diet alone, to 16.7 +/- 1.5 pmol/L during IGF-I) and serum connecting-peptide concentrations (2.14 +/- 0.89 mmol/L on diet alone, to 0.97 +/- 0.14 during IGF-I), while GH raised insulin (109.4 +/- 31.3 pmol/L, P less than 0.05 during GH) and connecting-peptide (3.12 +/- 0.59 mmol/L, P less than 0.02). At the dose of each hormone used, the attenuation of nitrogen wasting produced by infusions of IGF-I was similar in magnitude and timing to that produced by injections of GH. The reduction in serum glucose concentrations produced by IGF-I compared with the increase in glucose noted during GH treatment, could benefit hyperglycemic catabolic patients.