cssi/SciSciGPT-SciSciNet huggingface dataset:
Leukemia inhibitory factor modulates the peripheral immune response in a rat model of emergent large vessel occlusion.

The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke. Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or PBS at 6, 24, and 48 h prior to euthanization at 72 h. Bone marrow-derived macrophages were treated with LIF (20 ng/ml) or PBS after stimulation with interferon gamma + LPS. Western blot was used to measure protein levels of CD11b, IL-12, interferon inducible protein-10, CD3, and the LIF receptor in spleen and brain tissue. ELISA was used to measure IL-10, IL-12, and interferon gamma. Isolectin was used to label activated immune cells in brain tissue sections. Statistical analysis was performed using one-way ANOVA and Student’s t test. A Kruskal-Wallis test followed by Bonferroni-corrected Mann-Whitney tests was performed if data did not pass the D’Agostino-Pearson normality test. LIF-treated rats showed significantly lower levels of the LIF receptor and interferon gamma in the spleen and CD11b levels in the brain compared to their PBS-treated counterparts. Fluorescence from isolectin-binding immune cells was more prominent in the ipsilateral cortex and striatum after PBS treatment compared to LIF treatment. MCAO + LIF significantly decreased splenic levels of CD11b and CD3 compared to sham surgery. MCAO + PBS treatment significantly elevated splenic levels of interferon inducible protein-10 at 72 h after MCAO, while LIF treatment after MCAO returned interferon inducible protein 10 to sham levels. LIF administration with interferon gamma + LPS significantly reduced the IL-12/IL-10 production ratio compared to macrophages treated with interferon gamma + LPS alone. These data demonstrate that LIF promotes anti-inflammatory signaling through alterations of the IL-12/interferon gamma/interferon inducible protein 10 pathway.
Building a dendritic actin filament network branch by branch: models of filament orientation pattern and force generation in lamellipodia

We review mathematical and computational models of the structure, dynamics, and force generation properties of dendritic actin networks. These models have been motivated by the dendritic nucleation model, which provided a mechanistic picture of how the actin cytoskeleton system powers cell motility. We describe how they aimed to explain the self-organization of the branched network into a bimodal distribution of filament orientations peaked at 35° and − 35° with respect to the direction of membrane protrusion, as well as other patterns. Concave and convex force–velocity relationships were derived, depending on network organization, filament, and membrane elasticity and accounting for actin polymerization at the barbed end as a Brownian ratchet. This review also describes models that considered the kinetics and transport of actin and diffuse regulators and mechanical coupling to a substrate, together with explicit modeling of dendritic networks.
High-tide flooding disrupts local economic activity

Evaluation of observed sea level rise impacts to date has emphasized sea level extremes, such as those from tropical cyclones. Far less is known about the consequences of more frequent high-tide flooding. Empirical analysis of the disruption caused by high-tide floods, also called nuisance or sunny-day floods, is challenging due to the short duration of these floods and their impacts. Through a novel approach, we estimate the effects of high-tide flooding on local economic activity. High-tide flooding already measurably affects local economic activity in Annapolis, Maryland, reducing visits to the historic downtown by 1.7% (95% confidence interval, 1.0 to 2.6%). With 3 and 12 inches of additional sea level rise, high-tide floods would reduce visits by 3.6% (3.2 to 4.0%) and 24% (19 to 28%), respectively. A more comprehensive understanding of the impacts of high-tide flooding can help to guide efficient responses from local adaptations to global mitigation of climate change.
ACUTE AXILLARY ARTERY OCCLUSION AFTER TRANSRADIAL CORONARY CATHETERIZATION

Axillary artery occlusion following transradial cardiac catheterization (TRCC) has not been previously reported. 89-year-old woman with known chronic atrial fibrillation and hypertension presented to the emergency department with chest pain. Physical exam revealed an irregular rhythm, radial and
A Robust Dual-Axis Virtual Reality Platform for Closed-Loop Analysis of Insect Flight

Through evolution, insects have obtained magnificent skills to fly and navigate through cluttered environments. Many of these skills, which are utilized mid-air, often follow simple, yet robust and optimal algorithms, that may have useful applications in the field of unmanned aerial robotics. In this paper, we introduce a novel tethered flight platform for insects, capable of controlling the thrust and yaw in closed-loop conditions while exposing them to realistic visual stimuli. This enables precise reconstruction of the visual experience of the insect, allowing us to analyze and model visually guided behaviors of insects with precision and ease. We show this platform in action by exposing Queensland fruit flies (Bactrocera tryoni) to a realistic forest environment where the flies exhibit multi-modal behaviors at varying flight speeds.
Subduction Duration and Slab Dip

The dip angles of slabs are among the clearest characteristics of subduction zones, but the factors that control them remain obscure. Here slab dip angles and subduction parameters, including subduction duration, the nature of the overriding plate, slab age and convergence rate, are determined for 153 transects along subduction zones for the present‐day. We present a comprehensive tabulation of subduction duration based on isotopic ages of arc initiation and stratigraphic, structural, plate tectonic and seismic indicators of subduction initiation. We present two ages for subduction zones, a long‐term age and a reinitiation age. Using cross correlation and multivariate regression, we find that: (1) subduction duration is the primary parameter controlling slab dips with slabs tending to have shallower dips at subduction zones that have been in existence longer; (2) the long‐term age of subduction duration better explains variation of shallow dip than reinitiation age; (3) overriding plate nature could influence shallow dip angle, where slabs below continents tend to have shallower dips; (4) slab age contributes to slab dip, with younger slabs having steeper shallow dips; and (5) the relations between slab dip and subduction parameters are depth‐dependent, where the ability of subduction duration and overriding plate nature to explain observed variation decreases with depth. The analysis emphasizes the importance of subduction history and the long‐term regional state of a subduction zone in determining slab dip and are consistent with mechanical models of subduction.
What Is Natural Is Best: A Qualitative Exploration of Women’s Engagement in Attachment Parenting:

Attachment Parenting is a form of “intensive parenting” and involves a set of caretaking practices that are perceived by proponents of Attachment Parenting to nurture a strong maternal–child bond. ...
Computational chemistry modeling and design of photoswitchable alignment materials for optically addressable liquid crystal devices

Photoalignment technology based on optically switchable “command surfaces” has been receiving increasing interest for liquid crystal optics and photonics device applications. Azobenzene compounds in the form of low-molar-mass, watersoluble salts deposited either directly on the substrate surface or after dispersion in a polymer binder have been almost exclusively employed for these applications, and ongoing research in the area follows a largely empirical materials design and development approach. Recent computational chemistry advances now afford unprecedented opportunities to develop predictive capabilities that will lead to new photoswitchable alignment layer materials with low switching energies, enhanced bistability, write/erase fatigue resistance, and high laser-damage thresholds. In the work described here, computational methods based on the density functional theory and time-dependent density functional theory were employed to study the impact of molecular structure on optical switching properties in photoswitchable methacrylate and acrylamide polymers functionalized with azobenzene and spiropyran pendants.
The Lean Theorem Prover (System Description)

Lean is a new open source theorem prover being developed at Microsoft Research and Carnegie Mellon University, with a small trusted kernel based on dependent type theory. It aims to bridge the gap between interactive and automated theorem proving, by situating automated tools and methods in a framework that supports user interaction and the construction of fully specified axiomatic proofs. Lean is an ongoing and long-term effort, but it already provides many useful components, integrated development environments, and a rich API which can be used to embed it into other systems. It is currently being used to formalize category theory, homotopy type theory, and abstract algebra. We describe the project goals, system architecture, and main features, and we discuss applications and continuing work.
Hydrolysis of Retinol Palmitate by Rat Liver

Abstract Retinol acetate hydrolase is localized in rat liver microsomes whereas the retinol palmitate-hydrolyzing activity was found in the nuclear and in the mitochondrial lysosome-rich fractions. Acetone-dried powder from whole rat liver retained all of its retinol palmitate-hydrolyzing activity. Ammonium sulfate fractionation of the acetone-dried powder yielded a partially purified enzyme liberating 240 mµmoles of retinol per mg of protein per 60 min when retinol palmitate was used as substrate. The pH optimum was 8.6 and Km was 1.6 x 10-4 m. The enzyme was inhibited by ethanol, acetone, and Tween 80 and activated by bile salts. The activity of the enzyme was greatest for retinol palmitate, 60% lower for retinol acetate, and 70 to 90% lower for retinol oleate, linoleate, linolenate, stearate, myristate, and laurate. The liver enzyme efficiently hydrolyzed the retinol ester stored in the liver.
Foreign Exchange Rates

We establish a simple, yet completely general model for foreign exchange rates (FXR), in the context of multidimensional, possibly incomplete, Ito SDE market/econometric models. A very simple example is presented as well.
A 12,400 14C yr offshore diatom record from east central Lake Victoria, East Africa

The diatom record of V95-2P, a 7.6 m long sediment core collected from 67 m depth, is the first from the east central portion of Lake Victoria. A soil horizon developed at the coring site shortly before 12,400 14C yr BP due to a lakewide desiccation event. The radiocarbon chronology of the older half of this core is problematic, but if our estimated chronology is correct, then aridity and evaporative concentration of the lake are indicated by the presence of Thalassiosira rudolfi from > 12,400 BP to about 10,000 BP. Abundant Aulacoseira and generally rising biogenic silica concentrations may reflect enhanced water column mixing and rising precipitation:evaporation ratios ca. 10,000-8400 BP. A lakewide reorganization of diatom assemblages occurred around 7200 BP, when Aulacoseira nyassensis largely replaced A. granulata and after which rainfall and wind-driven mixing became more seasonally restricted. Pronounced reductions in offshore diatom deposition, from about 8300-5800 BP and after 3500 BP, may have been related to declines in the duration and/or intensity of wind-driven mixing. Increased aridity, and possibly deforestation in the lake basin, is indicated after 1400 BP.
Thermodynamics of Condensed Ionic Systems

In considering the thermodynamics of condensed ionic systems, primary emphasis will be given to those types which have not been widely investigated, at least until recently. Special attention will be given to systems continuously miscible from the fused salt to dilute solution in a polar solvent. Mixed fused salts will also be considered as well as phase separation and critical phenomena for any type of ionic system. The most important theories are given briefly; the status of more complex or less important theories is described. Semi-empirical equations are discussed where they are the best method of representing the experimental data.
Adapting Programs for Young Children

A summit meeting on young children’s mental health held in 2009 emphasized some important issues around the preschool developmental period (Society for Research in Child Development, 2009). One of the key issues was the importance of mental health for normal development. In addition, prevention strategies and evidence-based approaches were emphasized because these can decrease multiple risk factors. Important prevention strategies that were discussed included social and emotional learning programs, resilience, and helping children to recognize and regulate emotion.
Meal fatty acid uptake in human adipose tissue: technical and experimental design issues.

The adipose tissue uptake of dietary fat has been studied using fatty acid radiotracers incorporated into a meal, followed by adipose tissue biopsies. A number of experimental design issues, includ...
SEQUENTIAL VOTING WHEN LONG ELECTIONS ARE COSTLY

This paper analyzes sequential voting in binary elections when voters are motivated by a desire both to elect their preferred candidate and to avoid a long and costly election. I find a unique equilibrium in which a voter's action depends both on the intensity of the voter's preferences as well as how well the candidates have done in earlier voting rounds. This equilibrium results in momentum in which voters are more likely to vote for the candidate currently in the lead. Furthermore, the probability a voter votes for a candidate is increasing in the size of the candidate's lead. As a consequence, a candidate is more likely to win the election if the candidate's stronger supporters vote earlier in the election.
Absolute lymphocyte counts as prognostic indicators for immune thrombocytopenia outcomes in children

Background Recent studies reviewing immune mechanisms of immune thrombocytopenia (ITP) have suggested acute and chronic forms may represent distinct immunopathological disorders. This study evaluated absolute lymphocyte counts (ALCs) as predictors for ITP outcomes. Procedure CBCs with differential counts were ascertained at presentation, 3, 6, and 12 months for 204 patients. Receiver operating characteristic (ROC) curves were used to determine cutoff values. Logistic regression models and recursive partitioning were used to evaluate which variables were significantly associated with outcomes. Results ALC values at presentation were not independently predictive of disease duration. However, ALC values at 3 months were significant predictors. Sixty-eight percent (40/59) of patients >8 years of age and 43% (20/46) of patients ≤8 years who had an ALC ≤ 3,000/μl at 3 months developed chronic ITP. This compares to chronic rates of only 25% (3/12) and 2% (2/87) of patients >8 and ≤8 years, respectively, with an ALC > 3,000/μl at 3 months. Further, 92% (60/65) of patients who developed chronic ITP had a 3-month ALC ≤ 3,000/μl. An ALC > 3,000/μl at 3 months is a strong predictor for platelet recovery as only 5% (5/99) of these patients developed chronic ITP. Conclusion This study suggests progression to lower lymphocyte counts over the first few months of disease is a strong predictor for chronic ITP, allowing for risk stratification of patients, particularly when used in conjunction with other known predictors. Further research is needed to confirm these findings and to fully investigate the pathophysiological mechanisms responsible for this association. Pediatr Blood Cancer 2013;60:1967–1974. © 2013 Wiley Periodicals, Inc.
Practical application of process systems engineering to energy and resource conservation and management

Abstract Efficient computer-aided procedures are presented for estimating physical properties and thermodynamic functions of chemicals and materials species and for analyzing and synthesizing process system networks on the basis of thermodynamic criteria. It appears that these procedures are useful in minimizing difficulties invariably encountered in practical application of process systems engineering to energy and resource conservation and management. The difficulties arise mainly from two inherent complexities of a process system. One is the complexity of material species involved in the process, and the other the complexity due to the network structure of the process. The procedures are illustrated with these three realistic examples, two related to the estimation of physical properties and thermodynamic functions and one related to the thermodynamic analysis of a process system.
Cyclosporine Impairs Vasodilation Without Increased Sympathetic Activity in Humans

Abstract Hypertension and nephrotoxicity frequently complicate treatment with cyclosporine; two suggested mechanisms are increased sympathetic activity and altered vascular reactivity. It is difficult to assess these mechanisms in patients receiving cyclosporine after transplantation because of the accompanying major physiological alterations. Therefore, we studied 12 patients with rheumatoid arthritis twice—while they were taking and not taking cyclosporine. We measured vascular response in the dorsal hand vein using the linear variable differential transformer technique. Cyclosporine treatment significantly attenuated vasodilation induced by 60 ng/min isoproterenol (no cyclosporine, 19.8±3.5% versus cyclosporine, 7.9±2.2%; P =.02) and prostaglandin E 1 at 1000 pg/min (no cyclosporine, 72.6±10.2% versus cyclosporine, 45.6±9.0%) and 2000 pg/min (no cyclosporine, 100.8±14.7% versus cyclosporine, 68.6±8.0%; F=5.47, P =.047). However, neither vascular response to phenylephrine or nitroglycerin nor sympathetic activity assessed by measurement of norepinephrine spillover with a radioisotope dilution technique was affected by cyclosporine (no cyclosporine, 516.1±47.9 ng/min versus cyclosporine, 476.6±51.8 ng/min; P =.42). Cyclosporine impaired venodilation in response to two agonists that act through adenylate cyclase without altering α-agonist–induced venoconstriction or sympathetic activity. Therefore, in humans impaired vasodilation rather than sympathetic activation or enhanced vasoconstriction may be an important mechanism for the alterations of vascular tone that occur after long-term cyclosporine administration.
Research note: young children's resolution of distress through play.

SUMMARY It has been suggested that play is important to the young child as a means ofresolving a distressing experience. Pre-school children were observed as they exhibiteddistress on the first day of school. High- and low-anxiety children were allowedeither the opportunity for free play or participation in a story-reading session, eachof which was performed in either the presence or absence of peers. The anxiouschildren in the play condition were found to decrease in distress and their play wasmore solitary and imaginative in nature compared to other conditions. REFERENCESALEXANDER, F. (1958) A contribution to the theory of play. Psychoanal. Quart. 27, 175-193.BARNETT, L. A. and STORM, B. (1981) Play, pleasure and pain: the reduction of anxiety throughplay. Leisure Sci. 4, 161-175.CORTER, C. M., RHEINGOLD, H. L. and ECKERMAN, C. O. (1972) Toys delay the infant's followingofhis mother. Devi Psychol. 6, 138-145.DABBS, J. M., JOHNSON, J. E. and LEVENTHAL, H. (1968) Palmar sweating: a quick and simplemeasure./ exp. Psychol. 78,347-350.DOYLE, A., CONNOLLY, J. and RIVEST, L. (1980) The effect of playmate familiarity on the socialinteractions of young children. ChildDev. 51,217-223.ERIKSON, E. H. (1940) Studies in the interpretation of play: (1) Clinical observations of play dis-ruption in young children. Genet. Psychol. 22, 563-564.
Temporal progression of the host response to implanted poly(ethylene glycol)-based hydrogels

Poly(ethylene glycol) (PEG) hydrogels hold great promise as in vivo cell carriers for tissue engineering. To ensure appropriate performance of these materials when implanted, the host response must be well understood. The objectives for this study were to characterize the temporal evolution of the foreign body reaction (FBR) to acellular PEG-based hydrogels prepared from PEG diacrylate precursors when implanted subcutaneously in immunocompentent c57bl/6 mice by (immuno)histochemical analysis and gene expression. Compared with a normal FBR elicited by silicone (SIL), PEG hydrogels without or with a cell adhesion ligand RGD elicited a strong early inflammatory response evidenced by a thick band of macrophages as early as day 2, persisting through two weeks, and by increased interleukin-1β expression. PEG-only hydrogels showed a slower, but more sustained progression of inflammation over PEG-RGD. Temporal changes in gene expression were observed in response to PEG-based materials and in general exhibited, elevated expression of inflammatory and wound healing genes in the tissues surrounding the implants, while the expression patterns were more stable in response to SIL. While a stabilized FBR was achieved with SIL and to a lesser degree with PEG-RGD, the PEG-only hydrogels had not yet stabilized after 4 weeks. In summary, PEG-only hydrogels elicit a strong early inflammatory reaction, which persists throughout the course of the implantation even as a collagenous capsule begins to form. However, the incorporation of RGD tethers partially attenuates this response within 2 weeks leading to an improved FBR to PEG-based hydrogels.
Recovery of weight regulation following ablation of frontal cortex in rats.

Abstract Recovery of a postoperative weight loss following bilateral ablations of frontal cortex in rats was quicker when food pellets were scattered on the cage floor than when pellets were available only in attached food hoppers. Food deprivation prior to surgery facilitated recovery when food was scattered on the cage floor after surgery. Successive stage surgery also facilitated recovery. Despite and facilitative influences on recovery from the initial postoperative weight loss, all frontal rats showed a temporary weight loss 4–5 weeks after surgery if food previously available on the cage floor was removed (food remained in the hoppers). The results indicated that time per se after surgery and postoperative experience had different roles in recovery of function following brain damage.
Synthesis and characterization of low molecular weight oligomers of soluble polyaniline by electrospray ionization mass spectrometry

Abstract Mass spectrometry (MS) has not been utilized extensively for its ability to analyze the structure of polyaniline. This has been a result of polyaniline not being directly soluble in MS-“friendly” solvents. Here, low molecular weight oligomers of polyaniline are synthesized, using a modified room temperature synthesis of polyaniline, that are soluble in solvents that are better suited to electrospray MS analysis. Oligomers up to the 9-mer are identified from the mass spectra. Importantly, several different types of polyaniline oligomers that differ from one another based on their end groups were distinguished in the mass spectra. The use of tandem mass spectrometry (MS/MS) enabled identification of these various end groups.
Eudesmol isomers from Cordia trichotoma wood

Abstract White crystals derived from Cordia trichotoma wood during manufacture have been identified as a mixture of approximately 48 per cent α-, 35 per cent β-, and 13 per cent γ-eudesmol plus a trace of guaiol. Separation of the four compounds is possible by a combination of gas and preparative thin-layer chromatography.
Some effects of task relevance and friendship on helping: You don't always help the one you like☆

Abstract It was hypothesized that being outperformed on a task that is relevant to one's self-definition is threatening to self-esteem, and that this threat is greater when one is outperformed by a friend rather than by a stranger. When another's performance threatens self-esteem, persons will be less likely to help the other by making the task easy. To test these hypotheses, 52 friendship pairs participated with strangers in a word identification task described either as a measure of important skills (high relevance) or as a game (low relevance). Participants chose clues for both a friend and a stranger to use in identifying target words. As predicted, they gave harder clues under high-relevance than under low-relevance conditions. Moreover, they gave harder clues to strangers than to friends under low-relevance conditions, but gave harder clues to friends than to strangers under high-relevance conditions.
Aquaporin-4, homeostasis, and neurologic disease

Aquaporins constitute a family of water channels that regulate the transport of water in essentially all organs, including the kidney, gastrointestinal tract, secretory glands, inner ear, nervous system, and muscle.1–3 Because of his seminal discovery of aquaporins as the long-sought water channels,1 Peter Agre of Johns Hopkins University was awarded the Nobel Prize in Chemistry in 2003. Aquaporin-4 (AQP4) is the main aquaporin in the brain and is expressed in highest density in the perivascular and subpial astrocyte end-feet. Aquaporin-4 is a critical component of an integrated mechanism of regulation of cell volume and potassium (K+) homeostasis. Aquaporin-4 has been implicated in several neurologic conditions, including cerebral edema and seizures, and is the target of autoimmune attack in neuromyelitis optica (NMO). Recent studies on expression of and regulation of AQP4 provide testable hypotheses on the mechanisms of neural damage and make AQP4 a potential therapeutic target in these and other conditions. Aquaporins are water channels that consist of four identical subunits, each with six membrane-spanning α-helices.2,3 Aquaporin-4 is the most abundant aquaporin in the brain and is concentrated at glial–fluid interfaces, particularly in the perivascular and subpial end feet of the astrocytes (figure 1). Aquaporin-4 is also present on ependymal cells, and in low levels, on brain endothelial cells.3 The polarized distribution of AQP4 in the perivascular and subpial domains of the astrocytic plasma membrane results from its interaction with cytoskeleton and extracellular matrix proteins as part of the dystroglycan complex.4 At the astrocyte end foot process, AQP4 co-localizes with the …
Iteration method for the solution of integro-differential equations with constraints

We establish conditions for the existence of solutions of boundary-value problems for integro-differential equations with constraints and substantiate the application of the iteration method to the solution of these equations.
Crossover from incoherent to coherent phonon scattering in epitaxial oxide superlattices

Understanding the thermal transport properties of superlattice structures is relevant to a number of possible practical applications. Now, the scattering of phonons in oxide superlattices is shown to undergo a crossover from an incoherent to a coherent regime, which in turn strongly alters their thermal behaviour.
Relative Chlorinating, Nitrating, and Oxidizing Capabilities of Neutrophils Determined with Phagocytosable Probes

The capabilities of stimulated neutrophils to initiate intraphagosomal and extracellular chlorination, nitration, and other oxidative reactions has been evaluated using a fluorescent particle and soluble phenolic compounds as target molecules. Neutrophils activated by the soluble stimulus, phorbol myristate acetate, both chlorinated fluorescein that was covalently attached to polyacrylamide microspheres and initiated tyrosine dimerization. When nitrite ion was present at millimolar concentration levels in the medium, nitration of the phenolic rings also occurred; the relative extent of nitration increased as the nitrite concentration was increased. Myeloperoxidase (MPO) also catalyzed nitration and chlorination of fluorescein and the fluorescein-conjugated particles in cell-free solutions; the relative nitration yields increased with increasing [NO2-]/[Cl-] ratios. Nitration did not involve intermediary formation of nitrating agents derived from reaction between MPO-generated HOCl and NO2- because this reaction also occurred in chloride-free media and direct addition of HOCl to solutions containing NO2- and fluorescein gave only chlorinated products. In marked contrast to these extracellular reactions, intraphagosomal nitration of the fluorescein-conjugated particles could not be detected (even at [NO2-] as high as 0.1 M), whereas chlorination of the probe was extensive. These data indicate that intraphagosomal aromatic nitration in neutrophils is negligible, although extracellular nitration of phenolic compounds by secreted MPO could occur at physiological concentration levels of NO2-.
Ganglioside loading of cultured fibroblasts: a provocative method for the diagnosis of the GM2 gangliosidoses.

Abstract Confirmation of deficient β-hexosaminidase activity in suspected cases of G M2 gangliosidosis may be difficult with available assay systems if the residual activity is high (as in many juvenile cases and genetic compounds). Hexosaminidase activity is normal in the AB-variant (activator protein deficiency), although G M2 -ganglioside (G M2 ) catabolism is severely impaired. We therefore examined ganglioside degradation in intact fibroblasts in culture. Intracellular ganglioside levels were determined in cultured human skin fibroblasts grown in standard tissue culture medium or medium supplemented with mixed bovine brain gangliosides. Cellular uptake and catabolism of the added gangliosides were manifested by modest increases in the intracellular concentrations of gangliosides G T + G D and G M1 in all cells tested, and marked accumulation of G M2 in fibroblasts from patients with G M2 gangliosidoses. Intracellular G M2 increased five-to fifteen-fold in all of the G M2 gangliosidosis cell lines tested, including those from patients with infantile Tay—Sachs disease (TSD), Sandhoff disease, late infantile and juvenile variants of TSD with high residual enzyme activity, adult onset G M2 gangliosidosis, and the AB-variant. Significant GM2 accumulation did not occur in fibroblasts from patients with G M2 gangliosidosis grown in standard medium, or in normal fibroblasts grown in ganglioside enriched medium. Our method of ganglioside feeding employs commercially available materials and no special equipment. It should be useful for the confirmation of impaired G M2 catabolism in a variety of settings.
Aneuploidy is permissive for hepatocyte-like cell differentiation from human induced pluripotent stem cells

The characterization of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) routinely includes analyses of chromosomal integrity. The belief is that pluripotent stem cells best suited to the generation of differentiated derivatives should display a euploid karyotype; although, this does not appear to have been formally tested. While aneuploidy is commonly associated with cell transformation, several types of somatic cells, including hepatocytes, are frequently aneuploid and variation in chromosomal content does not contribute to a transformed phenotype. This insight has led to the proposal that dynamic changes in the chromosomal environment may be important to establish genetic diversity within the hepatocyte population and such diversity may facilitate an adaptive response by the liver to various insults. Such a positive contribution of aneuploidy to liver function raises the possibility that, in contrast to existing dogma, aneuploid iPSCs may be capable of generating hepatocyte-like cells that display hepatic activities. We examined whether a human iPSC line that had multiple chromosomal aberrations was competent to differentiate into hepatocytes and found that loss of normal chromosomal content had little impact on the production of hepatocyte-like cells from iPSCs. iPSCs that harbor an abnormal chromosomal content retain the capacity to generate hepatocyte–like cells with high efficiency.
The Chemical Basis of Pharmacology

Molecular biology now dominates pharmacology so thoroughly that it is difficult to recall that only a generation ago the field was very different. To understand drug action today, we characterize the targets through which they act and new drug leads are discovered on the basis of target structure and function. Until the mid-1980s the information often flowed in reverse: investigators began with organic molecules and sought targets, relating receptors not by sequence or structure but by their ligands. Recently, investigators have returned to this chemical view of biology, bringing to it systematic and quantitative methods of relating targets by their ligands. This has allowed the discovery of new targets for established drugs, suggested the bases for their side effects, and predicted the molecular targets underlying phenotypic screens. The bases for these new methods, some of their successes and liabilities, and new opportunities for their use are described.
Quality of care: do we care?

Abstract ▪ The quality of U.S. health care must improve. Practicing physicians need to become involved in generating new knowledge about what does and does not work in medical practice. Physicians ...
Job Complexity as Perceived by Workers and Experts.

Following a symbolic interactionist framework, a study of Chicago-area women aged 25 to 54 focused on their constructed reality including definitions of the complexity of their job. Women in even low status and task complexity occupations, as measured by Duncan and DOT scales, found some dimensions of their jobs “above average”—such as independence, responsibility, opportunities to see the product of the work, and opportunities for self-development—and were pleased by this level of perceived job complexity. There are women who feel their jobs are below average along these dimensions and are pleased with this situation, but there are fewer of them than the stereotypes of female workers predict. Women appear to judge their jobs from a social role rather a task perspective, which probably accounts for the relatively low fit between their evaluations of job complexity and the Duncan socioeconomic index or The Dictionary of Occupational Titles' complexity scale.
INACTIVATION BY MONOCHROMATIC NEAR-UV RADIATION OF AN Escherichia coli hemA8 MUTANT GROWN WITH AND WITHOUT δ-AMINOLEVULINIC ACID: THE ROLE OF DNA vs MEMBRANE DAMAGE

— Escherichia coli strain RT8 hemA8 [blocked in biosynthesis of δ-aminolevulinic acid (δ-ALA), and unable to manufacture porphyrins unless exogenously supplied with δ-ALA] is inactivated more efficiently by monochromatic 334- and 405-nm radiations if the cells are grown with δ-ALA supplementation. The fiuence enhancement factor for δ-ALA sensitization is larger for light at 405 nm than at 334 nm. Both irradiation conditions (plus or minus δ-ALA) showed prominent oxygen enhancement ratios, which were also larger at 405 nm than at 334 nm. At 334 nm, δ-ALA supplementation did not affect the accumulation of DNA breaks, while at 405 nm, the induction of DNA breaks doubled for cells supplemented with δ-ALA. Rubidium leakage caused by 405-nm radiation occurred at a smaller fiuence in cells supplemented with higher concentrations of δ-ALA than in cells supplemented with a lower concentration. The results suggest that (1) porphyrin derivatives may have a role in cell killing by near-UV radiations, and (2) damage to cytomembranes may be a critical lesion produced by these events, whereas DNA breakage may not.
Effect of Continuous Ambulatory Peritoneal Dialysis on Blood Pressure Control

To assess the efficacy of blood pressure control in continuous ambulatory peritoneal dialysis (CAPD), blood pressure was examined sequentially in 63 CAPD patients transferred from hemodialysis (HD), and in 97 patients started de novo on CAPD (NEW), over periods ranging from 3 to 63 months. Blood pressure changes were related to changes in body weight, hematocrit, and treatment with recombinant human erythropoietin (rHu-EPO), as well as to changes in antihypertensive drug requirements. Both groups of patients showed an immediate improvement in blood pressure control at 1 month, as manifested by an absolute decrease in blood pressure in HD patients (-4.3% +/- 2.1% [SEM], P < 0.05) and by a decrease in antihypertensive drug requirements in NEW patients (from 78% to 43.3%). This early improvement in blood pressure appeared to be volume-related, as reflected by changes in body weight. Both groups showed an additional decrement in blood pressure at approximately 6 months (-7.8% +/- 2.6% [SEM], P < 0.05, HD group; -3.4% +/- 2.4% [SEM], P < 0.05, NEW group). Treatment of anemia with rHu-EPO in 22 of the CAPD patients had no effect on blood pressure. CAPD thus appears to be more effective than HD in controlling blood pressure.
Binding of α-bungarotoxin to chick sympathetic ganglia: properties of the receptor and its rate of appearance during development

Studies were carried out on the binding of [125I]α-bungarotoxin (αBT) to membrane fragments of chick sympathetic ganglia. Specific binding of toxin was saturable with aKDof1.1nM. The rates of association and dissociation of the toxin from ganglionic membranes were4.3 × 104 M−1sec−1and4.6 × 10−5sec−1 (t1/2=4.2h). respectively. Binding was inhibited (by up to 95%) by low concentrations of nicotinic, but not by a muscarinic cholinergic ligand. The properties of the ganglionic binding site for αBT were consistent with its being a nicotinic acetylcholine receptor. The development of toxin receptors in chick ganglia was also studied. From days 7 to 11 in ovo, few receptors were present; from days 12 to 20 in ovo, there was a 10-fold increase in receptor number per ganglion; from hatching to maturaty, the number receptor per ganglion slowly increased and reached a maximum of 14 fmoles. The ontogeny of receptors for αBT in sympathetic appears to correlate with the cytological maturation and innervation of the principal neurons.
Prognostic factors in the radiotherapy of graves' ophthalmopathy

Abstract Between April 1968 and February 1988, 311 patients with symptomatic and progressive Graves' ophthalmopathy were treated with megavoltage orbital radiotherapy. The patients were divided into three groups: I (156 patients) treated with 20 Gy/2 weeks; II (69 patients) treated with 30 Gy/3 weeks, and III (a most recent set of 86 patients) received 20 Gy/2 weeks. The degree of eye involvement was evaluated numerically before and after therapy for each of five parameters: soft tissue signs, proptosis, eye muscle impairment, corneal involvement, and sight loss. Pre-treatment and current thyroid diagnosis and status were also noted. To evaluate the effects of radiotherapy alone, follow-up was terminated at the time any eye surgery was done; for those not treated surgically the minimum follow-up was 12 months. Because there were significant demographic differences between the patient groups, the results of each group were analyzed separately. A stepwise linear regression analysis was performed to determine if there were any significant variables affecting outcome. Based on these data formulae were derived which enable outcome to be predicted in any patient. Before therapy more than 90% of patients in all groups had soft tissue and eye muscle involvement, whereas 65–75% had proptosis and about half 50% had some degree of sight loss. Radiotherapy arrested progression of ophthalmic parameters in all but 1–6% of the patients. Objective and symptomatic improvement was noted for all parameters assessed, but there was marked individual variability. The best responses were noted for soft tissue, corneal involvement, and sight loss; however over half the patients had some improvement in eye muscle function and proptosis. Factors which resulted in less favorable outcome included male gender, advanced age, need for concurrent therapy for hyperthyroidism, and no history of hyperthyroidism. No complications have been observed. No significant differences in outcome were observed between the two dosage schedules. Following radiotherapy 29% of patients subsequently underwent some form of eye surgery, mostly eye muscle surgery to correct diplopia. After radiotherapy corticosteroid therapy was stopped without relapse in 76%. Orbital radiotherapy can result in improvement in signs and symptoms of Graves' ophthalmopathy in the majority of patients. For the remainder of patients the disease manifestations can be stabilized to allow functional surgical correction.
Burseraceae endémicas del Perú

La familia Burseraceae es reconocida en el Peru por presentar seis generos y 50 especies (Brako & Zarucchi, 1993; Ulloa Ulloa et al., 2004), todos ellos arboles. En este trabajo se reconoce dos endemismos en dos generos. Estos taxones endemicos ocupan las regiones Bosques Humedos Amazonicos y Bosques Muy Humedos Premontanos, entre los 150 y 1300 m de altitud. Ninguno de ellos se encuentra representado dentro del Sistema Nacional de Areas Naturales Protegidas por el Estado.
Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders.

When subjected to excessive oxidative stress, neurons may respond adaptively to overcome the stress, or they may activate a programmed cell death pathway called apoptosis. Apoptosis is characterized by alterations in mitochondria and the endoplasmic reticulum and activation of cysteine proteases called caspases. Increasing evidence suggests that apoptotic biochemical cascades are involved in the dysfunction and death of neurons in neurodegenerative disorders such as Alzheimer's, Parkinson, and Huntington's diseases. Studies of normal aging, of genetic mutations that cause disease, and of environmental factors that affect disease risk are revealing cellular and molecular alterations that may cause excessive oxidative stress and trigger neuronal apoptosis. Accumulation of self-aggregating proteins such as amyloid β-peptide, tau, α-synuclein, and huntingtin may be involved in apoptosis both upstream and downstream of oxidative stress. Membrane-associated oxidative stress resulting in perturbed lipid metaboli...
Regulation of skeletal muscle protein metabolism in catabolic states.

Purpose of reviewThis review highlights recent publications dealing with the nature of the in-vivo response of skeletal muscle to critical illness and approaches to attenuating this response. Studies focused on molecular mechanisms of muscle catabolism are not reviewed.Recent findingsThe general are
Otolaryngologic manifestations of immunodeficiency

As the initial conduit for respiration and alimentation, the upper aerodigestive tract is an obvious portal of entry for microorganisms. A functioning immune system is required to prevent establishment of infection in the ear, nose, and throat as well as to prevent excessive penetration of microorganisms more distally into the respiratory and gastrointestinal tracts. Host defense of the upper aerodigestive tract depends on mechanisms of cellular and humoral immunity that are active throughout the body, and on specialized functions (such as mucociliary clearance and IgA antibody secretion) that are restricted to mucosal surfaces. Defects of these immune mechanisms lead to recurrent or unusually severe infections. Otolaryngologic presentations are common in the immunodeficient host: many immunodeficient patients initially present with typical infections of the head or neck including sinusitis, otitis media, cervical adenopathy, or infections of the oral cavity. Although most patients with severe immunodeficiency are unlikely to present undiagnosed to an otolaryngologist, otolaryngologists may play a critical role in the initial identification and preliminary work up of patients with more subtle defects. Otolaryngologists will often be confronted with patients who seem infectionprone and must decide which individuals deserve specialty referral or other further work up for suspected immunodeficiency. Suggested triggers for further evaluation of immune status are summarized in Box 1 [1,2]. Many primary immunodeficiencies are associated with syndromes whose nonimmune manifestations are of interest to otolaryngologists (colobomaheart-atresia-retardation-genital-ear [CHARGE] syndrome, Down syndrome, and others). The otolaryngologist is frequently intimately involved in the care of these children for management of nonimmune otolaryngologic
Financial Risk Management in the Design of Water Utilization Systems in Process Plants

This paper discusses techniques to design water utilization systems in process plants when the parameters, especially the loads of the contaminants, are uncertain. Financial risk management in such designs is discussed in detail. It is also managed in a noniterative fashion using a one-step procedure that incorporates financial risk management as a constraint in the design procedure.
Hydrologic and Atrazine Simulation of the Cedar Creek Watershed Using the SWAT Model

One of the major factors contributing to surface water contamination in agricultural areas is the use of pesticides. The Soil and Water Assessment Tool (SWAT) is a hydrologic model capable of simulating the fate and transport of pesticides in an agricultural watershed. The SWAT model was used in this study to estimate stream flow and atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine) losses to surface water in the Cedar Creek Watershed (CCW) within the St. Joseph River Basin in northeastern Indiana. Model calibration and validation periods consisted of five and two year periods, respectively. The National Agricultural Statistics Survey (NASS) 2001 land cover classification and the Soil Survey Geographic (SSURGO) database were used as model input data layers. Data from the St. Joseph River Watershed Initiative and the Soil and Water Conservation Districts of Allen, Dekalb, and Noble counties were used to represent agricultural practices in the watershed which included the type of crops grown, tillage practices, fertilizer, and pesticide application rates. Model results were evaluated based on efficiency coefficient values, standard statistical measures, and visual inspection of the measured and simulated hydrographs. The Nash and Sutcliffe model efficiency coefficients (ENS) for monthly and daily stream flow calibration and validation ranged from 0.51 to 0.66. The ENS values for atrazine calibration and validation ranged from 0.43 to 0.59. All ENS values were within the range of acceptable model performance standards. The results of this study indicate that the model is an effective tool in capturing the dynamics of stream flow and atrazine concentrations on a large-scale agricultural watershed in the midwestern USA.
Selectivity in mercury-copper and mercury-iron accumulation in plants

Hawaiian soils are enriched in Hg relative to TI, Cu and Fe. Among samples from Southeast Africa, Iceland and the Negev-Sinai region analyzed for Hg and Fe, only the African soils showed relative Hg enrichment. Plant samples analyzed exhibited even greater selective increases in Hg content over Cu and Fe, and although plant Hg levels were characteristically greater than those found in the surrounding soil the reverse was observed with the other metals. This selectivity was interpreted in terms of the distinctive properties of elementary Hg including high volatility and direct uptake by plant surfaces, and the ability of plants to concentrate ionic Hg from soils and to return it to the atmosphere as the element. It is suggested that the unusual features in the biogeochemical cycling of Hg may be applicable to certain other toxic elements, e.g., As and Se.