cssi/SciSciGPT-SciSciNet huggingface dataset:
Therapeutic benefits of calcium channel blockers in cyclosporine-treated organ transplant recipients: Blood pressure control and immunosuppression

Cyclosporine has dramatically improved the success rates for all forms of organ transplantation. However, its use is complicated by the frequent occurrence of hypertension and reversible nephrotoxicity. The iatrogenic hypertension induced by cyclosporine resembles a low-renin, salt-sensitive form of essential hypertension, which is often controlled with salt restriction and therapies counteracting renal salt acquisition, e.g., diuretics and calcium channel blockers (CCBs). CCBs may also counteract the direct vasoconstrictive effects of cyclosporine, as well as the effects of other vasoconstrictors, such as endothelin or thromboxane, that may be stimulated by cyclosporine. Additionally, CCBs may potentiate the immunosuppression of cyclosporine, yet minimize nephrotoxicity. We demonstrated that the in vitro combination of verapamil and cyclosporine had an additive inhibitory effect on the activation and function of human peripheral blood mononuclear cells in several assays of the afferent and efferent limbs of immunologic responses. This additive immunosuppression was not likely to have been related to these drugs' effects on interleukin-2 (IL-2) circuitry, since no additive inhibition of IL-2 production or IL-2 responsiveness was found. There was some additive inhibition of IL-2 receptor expression at the higher concentrations of verapamil and cyclosporine that were tested. Although the combination of verapamil and cyclosporine additively inhibited mitogen-induced 45Ca uptake, the inhibitory effect of cyclosporine appears to be due to an inhibition of lymphocyte activation rather than direct inhibition of calcium flux through the slow calcium channel, suggesting that the two drugs do not have additive effects in depressing the transmembrane flux of calcium. More recently, we have demonstrated that the inactive enantiomer of verapamil, which does not block the slow calcium channel, has identical immunosuppressive capabilities as the active enantiomer. Thus, the antiproliferative effect of verapamil is probably slow-calcium-channel independent and may represent the ability of the drug to interfere with muscarinic, alpha 1-adrenergic, or even opiate receptors on lymphocytes or to block lymphocyte potassium channels. An even better possibility is that verapamil may diminish necessary precursor molecule uptake into lymphocytes, since both the inactive and active isomeric forms of verapamil are capable of diminishing thymidine, uridine, and leucine incorporation into stimulated lymphocytes--necessary for DNA, RNA, and protein synthesis, respectively. These in vitro observations may have clinical applicability, as early studies demonstrate reduced rejection rates of cyclosporine-treated transplant patients receiving CCBs. Consequently, CCBs are important medications to be considered for use in cyclosporine-treated organ transplant recipients.
Prepubertal initiation of sexual experiences and older first partner predict promiscuous sexual behavior of delinquent adolescent males—Unrecognized child abuse?☆

Sexual experiences of 1580 delinquent adolescent males ages 9-19 years admitted to a juvenile detention center from January 1985 to July 1990 were determined through a structured health history interview. A total of 89.6% admitted to prior sexual activity; 26.8% claimed sexual experience by age 11 years. Only 3.2% reported sexual abuse or incest. Of 334 sexually active adolescents who revealed both age of their first partner and their age of first intercourse, 42% had their first experience with a female 2 or more years older. Males who had their first sexual experience before age 11 years or with a female 2 or more years older, reported significantly larger numbers of sexual partners in their lifetime and during the year preceding their incarceration. Girls with similar first sexual experiences in terms of age of initiation and age difference from partner are considered to be abused. Practitioners who work with children and adolescents need to recognize the possibility of sexual activity among pre-adolescent males and to be aware of its implications. Language: en
Factors affecting conflict and negotiation within an alliance

Abstract A simple experimental game was used to create two-player alliances within which conflict could occur. Conflict centered on how many resource units each player would contribute to meet the alliance purpose of warding off an external threat. The alliances varied in the proportion of the initial resource units which each player held. There were four conditions, 10 two-player alliances in each, in which the proportion of the resources held by the larger player were: .52, .65, .79, and .92. A rationale and a simple model are developed that predict within alliance conflict should be greatest in alliances with players having intermediate discrepancies in resource strengths and least where resource discrepancies are very small or very large. The records of the players' negotiations were coded for conflict, and the predicted relation was supported. It was also found that alliances high in internal conflict took greater risks of being destroyed by the external threat. Other findings based on qualitative evidence are: players that negotiated by written communication as compared to those using telephone communication, took much more time, used more formal and awkward language, and referred to past communications more often. Some effects of several networks of communication on the negotiations are also reported.
Piece-wise constant predictive feedback control of nonlinear systems

Abstract We investigate the problem of receding horizon control for a class of nonlinear processes. A computationally efficient method is developed to identify the optimal control action with respect to predefined performance criteria. Using Carleman linearization and assuming piece-wise constant control action, the state vector is discretized explicitly in time. The optimal control problem is then reformulated as a nonlinear optimization problem and is efficiently solved using analytically computed sensitivity functions and standard gradient-based algorithms.
Tm:fiber lasers for remote sensing

Tm:fiber lasers are an attractive choice for remote sensing of water under arid conditions, such as found on Mars. Renewed interest in Martian exploration and discovery of huge deposits of water at the Martian south pole fuel interest in a water vapor lidar. The potential for high efficiency and the robust and compact nature of fiber lasers are very attractive features. Laser diodes, suitable for pumping Tm:fiber lasers, operate around 0.8 μm. Tm:fiber lasers operate around 1.9 μm, in a strong water vapor absorption region. For the laser to be highly efficient, Tm:fiber lasers must operate with a quantum efficiency of two. That is, two laser photons are produced for one absorbed pump photon. The role the fiber material plays and the dynamics of the Tm self quenching process must be understood to optimize this device. Both the physics and experimental results will be presented.
The Effect of Regulated Competition on Pharmaceutical Advertising and Promotion

Pharmaceutical advertising and promotion are distinct in that the firm’s decisions are highly interconnected with issues surrounding consumer safety. Expenditure decisions must balance profitable demand expansions with potential regulatory actions, and depend on the nature of competition (monopoly versus oligopoly). We develop a model of the firm’s choice of expenditures under different competitive scenarios with consideration of possible regulatory action. We test the model’s predictions with data from the market for erectile dysfunction drugs, which is ideal for analysis as it experienced an abrupt shift in structure and faced regulatory action. We find that advertising and promotion expenditures increase sales but the magnitudes are sensitive to competition and regulation.
Collaborative Visioning or Urban Planning as Therapy? The Politics of Public-Private Policy Making

One aspect of a recent restructuring of urban economies, societies, and spaces has been a change in urban planning practice. Planning is increasingly privatized and decentralized in U.S. cities. Private planning consultants are often hired by public-private coalitions in order to shape the future of cities, while the planning processes they institute are frequently claimed to be consensus-based, collaborative, and inclusionary, rather than elite-centered and expert-driven. This paper discusses the use of “visioning”—an increasingly popular technique that develops goals for the future of a city through consensus-based meetings, open to all parties—as developed by New Century Lexington, a public-private planning initiative in Lexington, Kentucky. It argues that: (1) new public-private planning procedures, incorporating collaborative techniques, frequently become the institutional sites of political struggle over how future urban geographies are produced; (2) in order to understand the role of visioning in c...
Treadmill exercise duration and dyspnea recovery time in chronic obstructive pulmonary disease: effects of oxygen breathing and repeated testing.

Abstract Oxygen supplementation is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Although some COPD patients use oxygen after exercise to relieve dyspnea, the effect of oxygen during recovery from exercise is not clearly understood. Exercise duration and dyspnea recovery time were studied in 18 patients with stable COPD. Patients exercised at a constant submaximal work rate on a treadmill ergometer until they no longer wished to continue. Oxygen, room air and compressed air were randomly administered in three consecutive post-exercise recovery periods. Dyspnea was scored on a 100 mm visual analog scale at 30 s intervals until return to baseline. An additional 20 minute post-recovery resting period was allowed between each test. No significant differences were found in dyspnea recovery time breathing oxygen (271 s), room air (290 s) or compressed air (311 s). When the groups were sorted by sequence of testing, there was a highly significant increase in recovery time (208 s, 307 s and 358 s for the first, second and third tests; P
Morphology of Critical Nuclei in Solid-State Phase Transformations

Predicting the shape of a critical nucleus in solids has been a long-standing problem in solid-state phase transformations. We show that a diffuse-interface approach together with a minimax algorithm is able to predict the critical nucleus morphology in elastically anisotropic solids without a priori assumptions. We demonstrate the possibility of nonconvex surfaces for critical nuclei. It is found that strong elastic energy contributions may lead to critical nuclei whose point group symmetry is below the crystalline symmetries of both the new and the parent phases.
Journal Vitality, Intellectual Integrity, and the Problems of McEthics

Good things have been happening to the Journal of Trauma & Dissociation (JTD). In this editorial, I first report on a number of these excellent developments. I also discuss one new concern for JTD—...
EEG sleep patterns as a function of normal and pathological aging in man

Abstract Four of five nights of uninterrupted recording of EEG and rapid eye-movement (EM) were obtained in fifteen young normal (YN), fifteen aged normal (AN) and fifteen chronic brain syndrome (CBS) subjects. All subjects were studied in the absence of drugs and with care taken to prevent daytime sleep. Compared to YN and AN groups, CBS subjects showed significantly lower values for total sleep time, emergent stage 1 EEG, EM activity and the latter two measures expressed as per cent of sleep time. Although the total amounts of NREM and REM sleep did not differ significantly for the YN and AN groups, the latter subjects manifested prolonged wakefulness and frequent interruptions of sleep. In these respects, results for the AN subjects were intermediate between those of the YN and CBS groups, differing significantly from both. The average durations of successive periods of NREM and REM sleep were similar in the YN and AN groups; in contrast, reduction in both stages of sleep led to an overall contraction of the sleep cycle in the CBS group. Statistically significant correlation coefficients were obtained between tests of cognitive function, independently administered and scored, and a number of sleep variables in both the AN and CBS groups. While brain metabolism and waking EEG have shown similar relationships in chronic brain syndrome, neither of these measures has been able to detect the more subtle changes in brain function that occur with normal aging. It therefore appears that the EEG of sleep may prove to be a diagnostic and research tool of special value to geriatric psychiatry. The quantitative changes in sleep with normal and pathological aging are similar to changes which take place in rate of overall brain metabolism. These findings, taken in association with the relationships of sleep variables to psychometric test scores in the AN and CBS group, are consistent with the hypothesis that sleep is intimately concerned with the central nervous system processes underlying cognition.
Antitumor Activity in Mice of Tentacles of Two Tropical Sea Annelids

Crude extracts of tentacles of two polychaetous annelids completely inhibit growth of Erlich ascites tumor in 60 to 100 percent of treated mice. Dialyzed extracts of one of these annelids, Lanice conchilega, show activity in the retentate after pronase digestion, suggesting that antitumor activity is associated with a nonprotein component of the crude tentacle extract.
Immunocytochemical and physiological evidence of a synapse between dopamine- and luteinizing hormone releasing hormone-containing neurons in the ewe median eminence.

Immunocytochemical labeling revealed that the arcuate nucleus (ARN) of the ewe's hypothalamus contains numerous tyrosine hydroxylase (TH)-positive neurons, that appear to lack dopamine-β-hydroxylase (DBH)-like immunoreactivity. Axons of these presumed dopaminergic neurons converge in the median eminence (ME) with Luteinizing Hormone Releasing Hormone (LHRH)-containing axons originating mostly from neurons situated in the medial preoptic area. Electron microscopic double labeling revealed synaptic contacts between TH-positive presynaptic profiles and LHRHcontaining postsynaptic elements. Samples of ME, ARN, paraarcuate and lateral hypothalamus were dissected and incubated to assess LHRH release and tissue content. Only ME-LHRH release was significantly reduced in the presence of dopamine (DA). All other regions released equal amounts with and without DA. Thus, a presynaptic dopaminergic inhibition of LHRH-containing axons at the level of the ME might contribute to the regulation of LHRH release into the po...
Speed Bumps, Potholes, And Tollbooths On The Road To Panacea: Making Best Use Of Data

Electronic health databases promise to transform both the assessment of health care delivery and our understanding of treatments’ safety and effectiveness. To achieve these goals, it will be necessary to (1) recognize limits on inferring causality; (2) protect confidentiality while allowing important societal gain; (3) link health data back to the individual patient; (4) obtain additional information from medical records; (5) understand ways in which electronic data can misrepresent reality; and (6) create the infrastructure, expertise, and resources to use the data. Realizing databases’ potential will require long-term commitment and investment beyond the maintenance of the databases themselves.
On the intrinsic force of convergence to stability.

Observed populations differ greatly in the speed with which they approach the stable form, but what determines rates of convergence is not fully understood. The present paper shows that the force of convergence does not approach a fixed value, but oscillates indefinitely around an “intrinsic”; level. That level, h∗, is determined by the square of the ratio of the 2 largest eigenvalues of the Leslie matrix. The value of h∗ can be closely approximated by a simple function that changes directly with the square of the coefficient of variation and inversely with the mean of the stable net maternity function. Population entropy, another measure of dispersion relative to the mean, is also highly correlated with h∗.
Studies on annealing and quenching of strontium barium niobate (sbn) single crystals: A-site cation ordering-disordering effect

Abstract Quenching and annealing studies have been carried out to investigate the effects of the A-site occupancy in the tungsten bronze structure on the polarization, pyroelectric coefficient, dielectric permittivity, and phase transition (Curie temperature range) behavior of ferroelectric relaxor Sr1−xBa x Nb2O6 (1−x = 0.75, 0.60, 0.50) single crystals. Quenching possibly generates a random distribution of vacancies between A1 and A2 sites and enhances the ordering of the cations in A-site. As a consequence of that, a Tc increase of as much as about 30°C above the Tc of non-quenched state has been observed. Quenching at a higher temperature, i.e., approximately about 1000°C results in reducing the ordering of the A-site because of random distribution of Sr2+, Ba2+, as well as vacancies. A continuous Tc increase accompanied by a decrease in dielectric permittivity and a broadened phase transition is reported and is believed to be due to strain built up because of energetically unfavored distribution of B...
Nonequilibrium DC and photon-assisted interlayer tunneling in a bi-layer tunneling structure

Abstract We study nonequilibrium DC and photon-assisted tunneling (PAT) of electrons between two weakly tunnel-coupled biased electron layers. The PAT current is related to the DC current. The line shape of the PAT current is studied as a function of the bias energy and the temperature. The contributions from the intrinsic screened electron–phonon and electron–electron scattering to the widths of the tunneling spectra are examined. Calculated DC tunneling current is compared with recent data.
Gut‐associated lymphoid tissue and dimethylhydrazine‐induced colorectal carcinoma in the wistar/furth rat

Although gut-associated lymphoid tissue in the form of discrete lymphoid patches (LP-GALT) in mammalian intestine in most prominent in the distal ileum, appendix, and, in some species, the cecal appendage, LP-GALT can be found throughout the intestinal tract. LP-GALT appears as single or multiple subepithelial lymphoid follicles covered by a specialized, structurally unique epithelium. In the colon of the Wistar/Furth (W/Fu) rat, LP-GALT appears as aggregates of follicles, or lymphoid patches, that can be detected macroscopically. We studied the relationship between 1,2-dimethylhydrazine- (DMH) induced colon carcinomas and the lymphoid patch associated epithelium in these animals. In addition, we defined the normal distribution of colonic lymphoid patches in both DMH-treated and control rats. Patches were found macroscopically and confirmed by histologic examination at five constant sites: lower pole of cecum, proximal ascending colon, the major colonic flexure, mid descending colon, and the rectosigmoid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be detected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be associated with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found associated with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium.
Surgical Reconstruction of the Cephalic Arch for the Management of Dysfunctional Brachiocephalic Arteriovenous Fistulas

ultrasound imaging at 1 year, 10 patients have no follow-up data (three of whom surgery was recently completed, seven of which were lost to followup), and eight patients experienced thrombosis. Stents extended into the inferior vena cava crossing the normal contralateral side in 45 of 66 patients (68%). Seven of these patients (15%) suffered new thrombosis of the nonstented contralateral side. Three of these seven patients were totally noncompliant with their postoperative anticoagulation; thus, 8% of compliant patients had new contralateral thrombosis after stenting across a normal contralateral common iliac vein and into the vena caval wall. Conclusions: To date, there is no consensus whether to stent across the thrombosed common iliac vein into the cava or completely across and into the vena cava. From these data it appears that stenting across the iliocaval confluence can result in a small percentage of contralateral thrombosis despite chronic therapeutic anticoagulation. This data will help us move forward in the development of new technologies and in the treatment of these patients.
Covariant elasticity and dislocations in smectic-C liquid crystals.

We derive a rotationally invariant form for the elastic energy of a smectic-C liquid crystal. The magnitude of the c director, but not its direction, can screen layer strain just as two independent components of the director screen strain in smectic-A liquid crystals. Type I and type II smectic-C liquid crystals can be classified according to whether the c-director penetration depth ${\ensuremath{\lambda}}_{\mathit{c}}$ is less than or greater than the smectic coherence length \ensuremath{\xi}. We calculate the energies of isolated dislocations and the interaction energies of parallel dislocations as a function of direction. We find an attractive interaction at large distances between like-sign screw dislocations and a repulsive interaction at short distances, leading to a minimum energy separation. (c) 1995 The American Physical Society
Cholic acid-oligonucleotide conjugates for antisense applications

Abstract To improve the pharmacokinetics of antisense oligonucleotides, cholic acid was conjugated to several biologically active sequences. Physical and biological properties of the conjugates were examined. While the cholic acid conjugation changes the lipophilicity of the oligonucleotides, the in vitro biological activity observed was dependent on the disease target, cell lines and the method of oligonucleotide treatment.
Using Conjoint Analysis To Value Ecosystem Change

Economists have developed a variety of methods to measure the values of environmental goods and services. Conjoint analysis (CJ) is a technique developed by mathematical psychologists to establish the structure of preferences across multi-attribute alternatives. It is a type of stated-preference method that has captured the attention of economists for purposes of analyzing preferences toward environmental goods and services. This paper outlines the applicability of CJ to environmental valuation, illustrates applications and valuation issues in the literature, and presents an application of CJ to valuing a Pennsylvania watershed quality improvement.
Vasoconstriction of canine coronary collateral vessels with vasopressin limits blood flow to collateral-dependent myocardium during exercise.

This study was performed to test the hypothesis that active constriction of coronary collateral vessels can worsen hypoperfusion of collateral-dependent myocardium during exercise. Studies were performed in seven adult mongrel dogs in which intermittent followed by permanent occlusion of the left circumflex coronary artery produced an area of collateral-dependent myocardium without gross evidence of infarct. Myocardial blood flow was determined with microspheres while measurement of aortic and distal coronary pressures allowed calculation of collateral and small vessel resistance at rest and during treadmill exercise. The ability of collateral vessel constriction to limit blood flow was assessed by infusion of vasopressin during exercise. During control conditions, blood flow in the collateral zone underwent a subnormal increase during exercise in comparison with the normal zone (1.74 +/- 0.27 versus 2.50 +/- 0.40 ml/min/g, respectively, p less than 0.05). Infusion of vasopressin in a dose that caused no change in normal zone flow (0.01 microgram/kg/min i.v.) produced a 30 +/- 5% further decrease in flow to the collateral zone (p less than 0.01). This decrease in collateral zone flow resulted from a 48 +/- 14% increase in transcollateral resistance in response to vasopressin infusion (p less than 0.01), as well as a 40 +/- 9% increase in small vessel resistance in the collateral zone (p less than 0.01). These data demonstrate that active constriction of both collateral vessels and coronary resistance vessels can contribute to hypoperfusion of collateral-dependent myocardium during exercise.
On the extinction characteristics of alcohol droplet combustion under microgravity conditions – A numerical study

Abstract Quasi-steady burning and extinction of droplets are of interest from both fundamental and application viewpoints. The latter is related to combustor performance and fire safety issues in reduced gravity environments. Influences of diluent in the atmosphere on isolated droplet combustion characteristics including extinction provide insights to fire extinguishment phenomena and the effectiveness of various diluents as fire suppressants. Extinction of pure methanol and methanol–water droplets ranging from 1.5 to 7 mm size, for varying levels of ambient carbon-dioxide, helium and oxygen concentration – burning in a quiescent microgravity environment were studied numerically to compare the effectiveness of fire suppressant diluent selection and determining the limiting oxygen index. The results show distinct regimes of diffusive and radiative extinction. The transition from diffusive to radiative extinction is strongly influenced by the ambient diluent selection, especially by carbon dioxide concentration. Results for helium as the diluent showed increased burning rate and extinction due to diffusive heat loss. An “ extinction characteristic ” correlation is proposed that depends on burning rate, ambient diffusivity and flame standoff ratio. Recent methanol droplet experiments conducted over a wide range of operating conditions onboard the International Space Station were found to yield results that agree well with the proposed “ extinction characteristic ” correlation.
Alarm pheromones of the Attini: Their phylogenetic significance

Abstract The volatile components present in the mandibular glands of a number of species of the attine genera Cyphomyrmex (1 species), Trachymyrmex (3 species), and Acromyrmex (2 species) were investigated and compared with those present in Atta. The extracts were found to consist of mixtures of a number of compounds. All but one of these mixtures contained some or all of the following compounds: 3-octanone, 4-methyl-3-heptanone, 3-octanol, and 4-methyl-3-heptanol. The behavioural responses of Trachymyrmex and Cyphomyrmex workers to these compounds were tested. A common chemical heritage based on 3-ketones and 3-alcohols appeared to exist among the genera studied. The chemical data were compared with an accepted phylogeny of these genera to see whether it supported the phylogeny.
Influencing database language standards

In this first article of the regular column on data base standardization activities, I give an overview of topic areas under active development in the formal national and international standardization bodies. I solicit contributions on these active topics so that standardizers and researchers can cooperate in the near term, before irreversible decisions are made, to produce the most useful and highest quality database standards.
Equilibrium and dynamic surface tension behavior of aqueous soaps: sodium octanoate and sodium dodecanoate (sodium laurate)

Abstract The dynamic surface tension behavior of sodium salts of fatty acids having eight (sodium octanoate) and twelve (sodium laurate) carbon atoms in pure water or in 0.1 N aqueous NaOH has been studied. The primary reason for this study was to obtain fundamental knowledge of the tension behavior of these molecules which are present in several consumer products. Tension data were obtained at a concentration of 30 mM for octanoate and 0.5–10 mM for dodecanoate at 25 and 37°C with the pulsating bubble surfactometer at constant or pulsating areas. In addition, the spinning bubble tensiometer and the Wilhelmy plate/Langmuir trough methods were used for better establishing reliable values of equilibrium tensions. An oscillating jet apparatus was used for obtaining estimates of tensions at small time-scales (3–10 ms). From these measurements, the most important factors affecting the dynamic tension behavior were the soap solubility, chain length, the aqueous medium, and the concentration. The equilibrium tension of aqueous sodium octanoate was determined to be about 40 mN m−1. Sodium octanoate was found to be very slow to equilibrate, with a time-scale of about 1000s. Aqueous sodium laurate has a longer chain length and is much faster to adsorb and more surface-active. The equilibrium tension was 23 mN m−1, and the time-scale of equilibration was very short. When tested in 0.1 N aqueous NaOH, sodium laurate showed much higher tensions. The tensions decreased with increasing concentration, as expected, and more strongly at the higher temperature.
Histones and Metal-Binding Domains

Jeremy M. Berg (1) describes potential metal-binding domains in nucleic acid-binding proteins. These metal-binding domains consist of sequences Cys-X_(2-4)-Cys-X_(4-15)-His-X_(2-8)-Cys. Berg also cites the fact that proteins known to bind ions have short sequences of the form Cys-X_(2-4)-Cys, Cys-X_(2-4)-His, or His-X_(2-3)-His. A well-known DNA-binding protein, histone H3, also has the conserved sequence Cys-Ala-Ile-His from residues 110 to 113 (2). The nucleosome octamer has two histones of each kind of four histones. These histones are organized about an axis of symmetry, such that these conserved sequences on each histone H3 oppose each other (3). The apposition of these two histone H3 sequences would generate a structure potentially able to coordinate a metal ion, namely 2(Cys-Ala-Ile-His).
Repeat Administration of Proteins to the Eye With a Single Intraocular Injection of an Adenovirus Vector

Delivery of therapeutic proteins, such as antiangiogenic proteins, to the eye is a demonstrated method for the control of age-related macular degeneration (AMD). However, one of the key limitations is the requirement for frequent and repeated intraocular injections. In this article, we demonstrate that repeated protein production in the eye can be stimulated from the cytomegalovirus (CMV) promoter without repeat intraocular injections using a small molecule, all-trans retinoic acid (ATRA). ATRA by systemic delivery can stimulate protein production multiple times in the eye. Administration of ATRA resulted in stimulation of gene expression to relevant levels that block abnormal blood vessel growth in an experimental animal model for AMD. These data support the principles of this technological discovery to therapeutic applications for chronic ocular diseases.
Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: possible involvement of mitochondrial S-adenosylmethionine transport.

Abstract Hepatocytes are resistant to tumor necrosis factor-α- (TNF) induced killing/apoptosis under normal circumstances, but primary hepatocytes from rats chronically fed alcohol have increased TNF cytotoxicity. Therefore, there must be mechanism(s) by which alcohol exposure “sensitizes” to TNF hepatotoxicity. Abnormal metabolism of methionine and S-adenosylmethionine (SAM) are well-documented acquired metabolic abnormalities in ALD. S-adenosylhomocysteine (SAH) is the product of SAM in hepatic transmethylation reactions, and SAH hydrolase (SAHH) is the only enzyme to metabolize SAH to homocysteine and adenosine. Our previous studies demonstrated that chronic intracellular accumulation of SAH sensitized hepatocytes to TNF cytotoxicity in vitro. In the current study, we extended our previous observations by further characterizing the effects of chronic alcohol intake on mitochondrial SAM levels in liver and examining its possible involvement in SAH sensitization to TNF hepatotoxicity. Chronic alcohol consumption in mice not only increased cytosolic SAH levels, but also decreased mitochondrial SAM concentration, leading to decreased mitochondrial SAM to SAH ratio. Moreover, accumulation of hepatic SAH induced by administration of 3-deaza-adenosine (DZA-a potent inhibitor of SAHH) enhanced lipopolysaccharide (LPS)/TNF hepatotoxicity in mice in vivo. Inhibition of SAHH by DZA resulted not only in accumulation of cytoplasmic SAH, but also in depletion of the mitochondrial SAM pool. Further studies using mitochondrial SAM transporter inhibitors showed that inhibition of SAM transport into mitochondria sensitized HepG2 cells to TNF cytotoxicity. In conclusion, our results demonstrate that depletion of the mitochondrial SAM pool by SAH, which is elevated during chronic alcohol consumption, plays a critical role in SAH induced sensitization to TNF hepatotoxicity.
Attentional guidance by working memory overrides salience cues in visual search

Many factors influence visual search, including how much targets stand out (i.e., their visual salience) and whether they are currently relevant (i.e., Are they in working memory?). Although these are two known influences on search performance, it is unclear how they interact to guide attention. The present study explored this interplay by having participants hold an item in memory for a subsequent test while simultaneously conducting a multiple-target visual search. Importantly, the memory item could match one or neither of two targets from the search. In Experiment 1, when the memory item did not match either target, participants found a high-salience target first, demonstrating a baseline salience effect. This effect was exaggerated when a high-salience target was in working memory and completely reversed when a low-salience target was in memory, demonstrating a powerful influence of working memory guidance. Experiment 2 amplified the salience effect by including very high-salience, “pop-out”-like targets. Yet this salience effect was still attenuated when the memory item matched a less salient target. Experiment 3 confirmed these were memory-based effects and not priming. Collectively, these findings illustrate the influential role of working memory in guiding visual attention, even in the face of competing bottom-up salience cues.
Factors influencing the variation in tenderness of seven major beef muscles from three Angus and Brahman breed crosses

Abstract Beef carcasses ( n = 30) from 3/4 Angus (A) × 1/4 Brahman (B), 1/4A × 3/4B, and 1/2A × 1/2B F 1 crosses were used to evaluate breed type, electrical stimulation, and postmortem aging on the M . semimembranosus (SM), M . semitendinosus (ST), M. biceps femoris (BF), M. vastus lateralis (VL), M. gluteus medius (GM), M. longissimus dorsi lumborum (LD), and M. triceps brachii (TB). Shear force values decreased with increased postmortem aging to a greater extent in steaks from 3/4A × 1/4B than steaks from the other breed types. Shear force values for steaks from the round (SM, ST, BF, VL) were higher than steaks from the loin (LD, GM) and chuck (TB) for both electrically stimulated and non-electrically stimulated muscles. In the LD muscle, calpastatin activities were similar among breed types. Muscle type played the greatest role in determining tenderness.
MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels.

Abstract Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA-/-) mouse. Here we show that MsrA-/- mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA-/- mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA-/- mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA-/- brains contained significantly higher levels of dopamine up to 12 months of age, while lower levels of dopamine were observed at 16 months of age. Moreover, striatal regions of MsrA-/- mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathways are impaired in MsrA-/- mice, which may contribute to their abnormal behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.
Cardiac, ventilatory and metabolic responses of two ecologically dissimilar species of fish to waterborne cyanide.

Changes in heart rate, ventilatory activity and oxygen consumption were determined in trout (Salmo gairdneri) and brown bullhead catfish (Ictalurus nebulosus) during exposure to a steadily increasing concentration of waterborne cyanide selected to produce death in 8–9 hours for each species. The lethal cyanide concentration for the bullheads was an order of magnitude higher than for trout. Trout developed an immediate and gradually increasing bradycardia throughout the exposure period. Cyanide produced tachycardia in the bullhead followed by a gradual onset of bradycardia as the concentration of cyanide was raised. Pericardial injection of atropine (a muscarinic cholinergic antagonist) indicated that bradycardia in the trout was due initially to increased vagal tone but later due to the direct effect of cyanide on the heart. Hyperventilation in the trout persisted throughout the exposure period, although the rate and amplitude fluctuated and was variable between individual fish. During the last hour of exposure (highest cyanide concentration), ventilation was characterized by rapid, shallow breaths followed by a sudden respiratory arrest. The bullheads exhibited hyperventilation during the first 3 hours of exposure followed by a gradual, linear drop in ventilation rate and amplitude until death occurred. Cardiac and ventilatory responses in both species were attributed to stimulation of central and peripheral chemoreceptors by cyanide. Evidence is presented which suggests the initial response in the bullheads was due, at least in part, to gustatory stimulation by the cyanide. Oxygen consumption of the trout remained above pre-exposure levels for the majority of the test period. Oxygen consumption in the bullhead paralleled the changes in heart and ventilatory rates. Whole-body lactate levels of fingerlings of both species during cyanide exposure were measured to estimate the extent of anaerobiosis. Whole-body lactate levels were much greater in the bullheads than the trout, indicating a higher capacity for anaerobiosis, possibly due to a greater fuel supply. Overall, the trout responded to cyanide in a manner similar to that produced by environmental hypoxia whereas the bullheads experienced a gustatory stimulus which masked the hypoxia-like response.
Protein Separations Using Membrane Filtration: New Opportunities for Whey Fractionation

There is considerable commercial interest in the preparation of individual whey proteins for food, nutraceutical, and therapeutic applications. Recent developments in membrane filtration have provided exciting new opportunities for large-scale protein fractionation. This manuscript provides an overview of the previous work on protein separations using membrane filtration, including the importance of solution pH and ionic strength to obtain very high resolution separations. Specific data are shown for the separation of hemoglobin from BSA and for the purification of immunoglobulins from a complex feed stream using a gradient diafiltration process. The potential applications of membrane systems for whey protein fractionation are also examined.
The Materials Genome Initiative, the interplay of experiment, theory and computation

Abstract Advances in theoretical, computational and experimental materials science and engineering offer not only the promise to accelerate the pace at which new materials are discovered, but also to reduce the time required to bring new products to market. The so-called Materials Genome Initiative seeks to capitalize on that promise by identifying innovative research paradigms that integrate theory, computation, synthesis, and characterization in manners that, until recently, were not possible. A workshop was held at the National Science Foundation in December of 2013 to identify some of the central challenges and opportunities facing materials research within the context of that initiative. This article summarizes the findings of the workshop, and presents a series of concrete recommendations with the potential to facilitate its implementation. It also provides an overview of timely fundamental, technical and logistical challenges, organized according to distinct classes of materials, whose solution could have significant practical and societal benefits.
Superconductivity of Itinerant Electrons Coupled to Spin Chains

Let us take as our starting point the Cu-O layers. The question is this: if one dopes the system away from half filling is there a mechanism that can lead to superconductivity? We will also assume that the carriers reside at the oxygen sites and that the spins in the copper sites provide an antiferromagnetic background for the former. A possible mechanism for pairing is due to spin polarons. Consider just one carrier: if there is a coupling between the spins of the itinerant electrons (IE) and the fixed spins (say ferromagnetic), then the carriers will prefer a ferromagnetic domain (aligned with its spin), i.e. a polaron. The polaron size will be determined by a competition between loss of exchange energy and localization energy. If a second carrier is now introduced, it will reside in the same polaron (if the coulomb interaction is not too strong) and also have its spin parallel to the first. Thus the polaron can lead to pairing in the spin 1 channel.
Hepatic encephalopathy after portacaval shunt in a noncirrhotic child.

PoRTACAVAL SHUNTING is performed in adults and chi ldren with familial ( type 2) hypercholesterolemia, to lower p lasma lipid levels and postpone atherosclerot ic changes. 1'2 A more common indicat ion for surgical shunting is ex t rahepat ic portal venous obstruction. 3' 4 In bo th of these disorders, pat ients have noncir rhot ic livers. A l though exper imental animals with noncir rhot ic livers f requent ly develop hepat ic encephalopathy af ter por tacaval shunt ing, adul t h u m a n s rarely do so, 5 and this complicat ion is said not to occur in children. W e describe in detail the first such case in a child, to which br ief reference was made in a paper by Starz l et al?
An NIC-based negative resistance circuit for microwave active filters

This article presents a method for synthesizing a negative resistance in MMIC technology. The circuit employed is a classical negative impedance converter (NIC) that has been terminated in an RLC one-port specially designed to compensate for the parasitics of the active and passive elements. The procedure, which effectively translates a nonideal NIC design task into a well-defined one-port synthesis problem, is demonstrated in computer simulation for a four-transistor MMIC network which achieves a purely real input resistance of −100 Ω over 1.5–2.5 GHz. An important application for NIC-based circuits of this type is in the design of microwave active filters. © 1994 John Wiley & Sons, Inc.
Influence of glutathione fructosylation on its properties

Incubation of fructose and glutathione leads to the formation of N-2-deoxy-glucos-2-yl glutathione as the major glycation product, with characteristic positive ion at 470 Th in LC-MS spectra. Glutathione disulfide and fructose generate two compounds: N-2-deoxy-glucos-2-yl glutathione disulfide (m/z=775 Th) and bis di-N,N'-2-deoxy-glucos-2-yl glutathione disulfide (m/z=937 Th). N-2-deoxy-glucos-2-yl glutathione is 2.5-fold less effective than glutathione in reducing dehydroascorbic acid. Glutathione peroxidase and glutahione-S-transferase exhibit marginal activity toward N-2-deoxy-glucos-2-yl glutathione, while glyoxalase I shows 44.9% of the enzyme's specific activity. Glutathione reductase demonstrates 6.9% of the enzyme's specific activity with bis di-N,N'-2-deoxy-glucos-2-yl glutathione, while with mono-N-glucosyl glutathione disulfide retained 5 6.1% of the original activity. Glutathione reductase could not reduce N-2-deoxy-glucos-2-yl glutathione in mixed disulfide with gammaS-crystallin, but reduced glutathione in mixed disulfide with gammaS-crystallin by 90%. The presence of N-2-deoxy-glucos-2-yl glutathione in mixed disulfide with gammaS-crystallin makes this molecule more susceptible to unfolding than native gammaS-crystallin.
Amplitude and Phase Adaptive Nulling With a Genetic Algorithm

This paper introduces amplitude and phase nulling with a genetic algorithm with the intent of finding the optimum number of LSB of control needed to place multiple nulls while not significantly distorting the far field pattern. Many interference scenarios were modeled and individual runs were averaged to conclude that five LSB of amplitude and three LSB of phase control out of a total of eight bits are best for the linear array modeled. Representative samples of some of the interference scenarios modeled are shown.
How much time do we have? Urgency and rhetoric in sustainability science

Sustainability challenges are multitudinous, urgent, and complex. They are beyond the capacities of our current institutions to address, caused by path-dependent behaviors, and require substantial change from systems with crippling inertia. These problems are born of large-scale industrial economic policy, the rise of materialism, and the supremacy of profit over sustainability. Currently, academia is poorly positioned to address sustainability problems because of anachronistic pedagogy, mismatched incentives, insufficient expertise, lack of personal commitment, and insular products and communication. What transformational methods for research and practice, which involve relevant communities throughout problem-solving processes in meaningful ways, does sustainability science offer? Though rhetoric outweighs real-world sustainability transitions so far, we argue that operationalizing the goals of the field, developing the necessary competencies, and seeking novel partnerships between society and the academy will position academic institutions to make a bigger impact on the transition to sustainability.
Isolation and composition of a glycopeptide from a phytohemagglutinin of Phaseolus vulgaris.

Abstract A glycopeptide was isolated from a Pronase digest of a phytohemagglutinin from Phaseolus vulgaris. This glycopeptide had a molecular weight of about 4380 and was composed of 12 amino acid residues (Asp6, Thr3, Glu2, Tyr) and 19 sugar residues. The carbohydrate moiety appears to be comprised of a complex heteropolysaccharide containing mannose5, arabinose5, galactose4, glucosamine2, glucose2, and fucose1.