cssi/SciSciGPT-SciSciNet huggingface dataset:
Structural Polymorphism of Human Islet Amyloid Polypeptide (hIAPP) Oligomers Highlights the Importance of Interfacial Residue Interactions

A 37-residue of human islet amyloid polypeptide (hIAPP or amylin) is a main component of amyloid plaques found in the pancreas of ∼90% of type II diabetes patients. It is reported that hIAPP oligomers, rather than mature fibrils, are major toxic species responsible for pancreatic islet β-cell dysfunction and even cell death, but molecular structures of these oligomers remain elusive. In this work, on the basis of recent solid-state NMR and mass-per-length (MPL) data, we model a series of hIAPP oligomers with different β-layers (one, two, and three layers), symmetries (symmetry and asymmetry), and associated interfaces using molecular dynamics simulations. Three distinct interfaces formed by C-terminal β-sheet and C-terminal β-sheet (CC), N-terminal β-sheet and N-terminal β-sheet (NN), and C-terminal β-sheet and N-terminal β-sheet (CN) are identified to drive multiple cross-β-layers laterally associated together to form different amyloid organizations via different intermolecular interactions, in which the...
Accountability, entitlement, tenure, and satisfaction in Generation Y

Purpose – Given the entitlement and job mobility associated with Generation Y, the purpose of this paper is to investigate the moderating effects of psychological entitlement and tenure on the felt accountability-job satisfaction relationship. Design/methodology/approach – Survey data from a sample of resident assistants were examined using hierarchical moderated regression analysis. Findings – Entitled employees responded to accountability favorably, demonstrating lower job satisfaction than non-entitled employees when accountability was low, but nearly equal levels when accountability was high. All participants reported higher job satisfaction when job tenure was lower, but entitlement-driven satisfaction differences were observed only when accountability was low. Research limitations/implications – Cross-sectional data warrants longitudinal replication to establish causation and to give insight into how much time must pass before accountability begins to reduce the negative effects of entitlement. Prac...
Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of α-helical and β-sheet protein domains

The fundamental fracture mechanisms of biological protein materials remain largely unknown, in part, because of a lack of understanding of how individual protein building blocks respond to mechanical load. For instance, it remains controversial whether the free energy landscape of the unfolding behavior of proteins consists of multiple, discrete transition states or the location of the transition state changes continuously with the pulling velocity. This lack in understanding has thus far prevented us from developing predictive strength models of protein materials. Here, we report direct atomistic simulation that over four orders of magnitude in time scales of the unfolding behavior of α-helical (AH) and β-sheet (BS) domains, the key building blocks of hair, hoof, and wool as well as spider silk, amyloids, and titin. We find that two discrete transition states corresponding to two fracture mechanisms exist. Whereas the unfolding mechanism at fast pulling rates is sequential rupture of individual hydrogen bonds (HBs), unfolding at slow pulling rates proceeds by simultaneous rupture of several HBs. We derive the hierarchical Bell model, a theory that explicitly considers the hierarchical architecture of proteins, providing a rigorous structure–property relationship. We exemplify our model in a study of AHs, and show that 3–4 parallel HBs per turn are favorable in light of the protein's mechanical and thermodynamical stability, in agreement with experimental findings that AHs feature 3.6 HBs per turn. Our results provide evidence that the molecular structure of AHs maximizes its robustness at minimal use of building materials.
Glucocorticoids and hypothalamic obesity.

Recent studies have demonstrated a role for adrenal glucocorticoid hormones in the hyperphagia and obesity which follow lesions of the ventromedial hypothalamus (VMH). Although VMH lesions elevate morning plasma corticosterone levels, it is concluded that this contributes little to the development of obesity. More importantly, animals with VMH lesions appear to be hyperresponsive to very low levels of circulating glucocorticoids. The overeating and obesity are both prevented and reversed by either complete adrenalectomy or complete hypophysectomy (i.e., resulting in plasma corticosterone levels of less than 1.0 microgram/dl) and restored by dosages of glucocorticoids that have no effect on feeding behavior and weight gain in nonlesioned adrenalectomized animals. Mineralocorticoid hormones have no effect on hypothalamic obesity. Judging by the time course of effects on feeding behavior in VMH-damaged mice of a single intracerebroventricular injection of a low dose of glucocorticoid, which has no effect when administered intraperitoneally, it is concluded that glucocorticoids exert their effect centrally in a permissive, rather than a regulatory, manner. Stimulation of the neighboring paraventricular nuclei (PVN) with norepinephrine or neuropeptide Y produces a rapid feeding response which is also abolished by adrenalectomy and restored with administration of glucocorticoids. However, it is unlikely that the PVN is the site at which glucocorticoids exert their effect in animals with VMH lesions, for PVN lesions or knife-cuts, or combination VMH-PVN lesions, also result in hyperphagia and obesity. It is concluded that adrenal glucocorticoid hormones exert their permissive effects on feeding behavior at brain sites other than the medial hypothalamus. The septo-hippocampal complex is suggested as a possible site.
Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo

Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fcγ receptor FcγRIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally deleted for FcγRIIB on defined cellular populations or mutated in specific signaling components, we now demonstrate that different agonistic anti-TNFR antibodies have specific requirements for FcγRIIB expression on defined cellular populations and function in trans in the absence of FcγRIIB signaling components, thus supporting a general mechanism of FcγRIIB cross-linking in vivo for the activities of these antibodies.
Biological effects of the Los Alamos Meson Beam on cells in culture

Preliminary measurements of the biological effects of negative pions on cells in culture are reported. Cell survival as a function of depth was obtained by using gelatin to suspend the cells. The results indicate that the effects are more pronounced at the peak portion of negative pions. Cell-survival curves were also obtained under oxygenated and hypoxic conditions. The biological effectiveness at the peak was found to be a factor of 2.0 higher than at the plateau. The oxygen enhancement ratio was 1.5 at the peak. No significant differences in biological effects were observed above 14 mm in the peak region.
Block-diagram solutions for vacuum-tube circuits

MANY AUTHORS1?7 of textbooks on electronics begin their discussion of feedback amplifiers with the block diagram given by Black.8 The general gain equation $A^{\prime} = {A \over 1-AB} \eqno{\hbox{(1)}}$ in which A is the gain without feedback and s is the feedback fraction, is then derived, and the beneficial effects of feed back are discussed. In dealing with specific circuits, however, it is a common practice to write and solve the circuit equations, and then to manipulate the resulting gain equation into a form in which A and s can be identified. In some cases, expressions for A and s are simply stated and verified by substitution into the general equation.
Kainate-induced seizure activity stimulates the polyamine interconversion pathway in rat brain

Systemic injection of kainic acid in adult rat is accompanied by a large increase in the accumulation of acetylated derivatives of spermidine and spermine in the hippocampus and piriform cortex of animals pretreated with the polyamine oxidase inhibitor, MDL 72527. Furthermore, the activity of the enzyme spermine/spermidine acetyltransferase is increased at 8 and 16 h after kainate injection in piriform cortex and hippocampus. These results indicate that the polyamine interconversion pathway is rapidly activated in limbic areas following kainate-induced seizure activity, and suggest that this pathway might participate in the resulting neuronal damage.
Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies.

Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies
Membrane abnormality in malignant hyperthermia.

In this study we report on the effect of halothane exposure on the skeletal muscle membrane and calcium localization in 9 patients with confirmed susceptibility to malignant hyperthermia and compare them with 11 non-susceptible cases of malignant hyperthermia. Two normal muscle specimens with physiologically induced muscle contractures were also included for comparison. Halothane exposure in malignant hyperthermia-susceptible cases showed severe muscle contractures, definite breaks in the plasma membrane with peroxidase penetration, and large number of calcium granules within the mitochondria and sarcoplasmic reticulum. Malignant hyperthermianon-susceptible cases and muscle with physiological contractures did not show discontinuity of the plasma membrane or excessive calcium deposits. Based on these findings we conclude that the halothane exposure in malignant hyperthermia-susceptible patients causes breaks in the muscle plasma membrane.
Health-related quality of life functioning over a 2-year period in children with end-stage renal disease

Background Optimal care of the pediatric chronic kidney disease/end stage renal disease (CKD/ESRD) patient must now incorporate health-related quality of life (HRQOL) assessment and management.
First principles linear response calculations of lattice dynamics for CuCl

CuCl is known to exhibit large anharmonic effects and possibly a complicated multiwell Born-Oppenheimer surface reminiscent of the instabilities in perovskite ferroelectrics and cuprate superconductors. However, we have determined its phonon dispersion from first principles calculations and find it to agree well with low temperature experimental results. The calculations were carried out using a linear response formalism based on the linearized augmented plane wave method within the local density approximation. The calculated Born effective charges are within 10% of experiment and the high frequency dielectric constant ${\mathrm{\ensuremath{\epsilon}}}_{\mathrm{\ensuremath{\infty}}}$ is about 30% larger than the experimental value. This level of agreement is comparable to that attained in simpler semiconductors.
Nuclear–mitochondrial discordance and gene flow in a recent radiation of toads

Natural hybridization among recently diverged species has traditionally been viewed as a homogenizing force, but recent research has revealed a possible role for interspecific gene flow in facilitating species radiations. Natural hybridization can actually contribute to radiations by introducing novel genes or reshuffling existing genetic variation among diverging species. Species that have been affected by natural hybridization often demonstrate patterns of discordance between phylogenies generated using nuclear and mitochondrial markers. We used Amplified Fragment Length Polymorphism (AFLP) data in conjunction with mitochondrial DNA in order to examine patterns of gene flow and nuclear–mitochondrial discordance in the Anaxyrus americanus group, a recent radiation of North American toads. We found high levels of gene flow between putative species, particularly in species pairs sharing similar male advertisement calls that occur in close geographic proximity, suggesting that prezygotic reproductive isolating mechanisms and isolation by distance are the primary determinants of gene flow and genetic differentiation among these species. Additionally, phylogenies generated using AFLP and mitochondrial data were markedly discordant, likely due to recent and/or ongoing natural hybridization events between sympatric populations. Our results indicate that the putative species in the A. americanus group have experienced high levels of gene flow, and suggest that their North American radiation could have been facilitated by the introduction of beneficial genetic variation from admixture between divergent populations coming into secondary contact after glacial retreats.
Nucleotides that contribute to the identity of Escherichia coli tRNAPhe

Abstract A series of sequence variants of amber suppressor genes of tRNA Phe were synthesized in vitro and cloned in Escherichia coli to examine the contributions of individual nucleotides to identity for amino acid acceptance. Three different but complementary types of tRNA variants were constructed. The first involved the substitution of base-pairs on the cloverleaf stem regions of the E. coli tRNA Phe . The second type of variant involved total gene synthesis based on wild-type tRNA Phe sequences found in Bacillus subtilis and in Halobacterium volcanii . In the third type of variant, the identity of E. coli tRNA Lys was changed to that of tRNA Phe . The nucleotides which are important for tRNA Phe identity in E. coli are located on the corner of the L-shaped tRNA molecule, where the dihydrouridine loop interacts with the T loop, and extend to the interior opening of the anticodon stem and the adjoining variable loop. The nucleotide sequence on the dihydrouridine stem region, which joins the corner and stem regions, was not successfully studied though it may contribute to tRNA Phe identity. The fourth nucleotide from the 3′ end of tRNA Phe has some importance for identity.
Broadening horizons: holistic viewpoints from the Biology of Genomes

A report on the Cold Spring Harbor Laboratory 27th annual meeting on the Biology of Genomes, held in Cold Spring Harbor, New York, USA, 6-10 May 2014.
The effects of mass transport and chemical reaction on pollutant removal in a three-phase slurry adsorber-reactor

The analysis of the effects of mass transport and chemical reaction on pollutant removal from a gas-phase in a three-phase slurry adsorber-reactor is presented. A mathematical model, consisting of four coupled differential equations, was developed to describe the process and solved numerically. The modeling assumptions included: perfect mixing in the three-phase slurry, Henry's law, a linear adsorption isotherm and a second order, irreversible chemical reaction. The model was found to adequately represent limited existing experimental data and to qualitatively predict the effects of the various transport coefficients on the pollutant removal efficiency of the process. The model was also used for design analysis. Although the model-process achieved significant pollutant removal for representative operating conditions, the percent removal was ultimately limited by mass transport from the gas bubbles to the liquid slurry. On presente une analyse des effets du transfert de masse et d'une reaction chimique sur la separation d'un agent polluant d'une phase gazeuse, dans un reacteur-adsorbeur a trois phases. On a etabli un modele mathematique, comprenant quatre equations differentielles simultanees, pour decrire le processus et une solution numerique est donnee. Les hypotheses du modele comportaient les points suivants: (a) agitation ideale du systeme a trois phases, (b) loi de Henry, (c) isotherme d'adsorption lineaire et (d) reaction chimique irreversible de second ordre. On a trouve que le modele representait bien les quelques resultats experimentaux connus, et permettait de prevoir qualitativement les effets des divers coefficients de transfert sur l'efficacite du processus de separation de l'agent polluant. On a aussi utilise ce modele pour l'analyse de procedes. Bien que le processus utilise avec ce modele permettre de realiser une bonne separation de l'agent polluant dans des conditions caracteristiques des conditions operatoires, l'efficacite de la separation a ete finalement limitee par le transfert de masse entre les bulles de gaz et la partie liquide du systeme.
The Changing View of Property Rights in Natural Resources Management

. The social, demographic, technological, and ecological circumstances in the United States have changed since its beginning. Society's view of property rights—i.e., the way resources are to be used—has evolved accordingly. Resource owners’virtually unrestricted right to use their property as they wished disappeared along with the western frontier, pristine wilderness, and abundant natural resources. There is now a strong commitment to preserve what little nature and resource are left. To overcome the problem of abuse or destruction of nature, it is necessary to recognize, first and foremost, that the problem has become institutionalized over the years and, secondly, that humans and natural objects are interdependent and are of roughly equal importance in the biotic community. Protection of nature against abuse therefore requires that nature be granted legal rights on moral grounds, that consequently human decisions and actions must take into consideration their impacts on nature, and that defenders of nature be able to raise its rights in its own name in any administrative or legal dispute.
Policies for risk assessment in federal land and resource management decisions

Abstract Laws and policies require federal land and resource management agencies, and regulatory agencies charged with conserving imperiled species, to assess risks associated with proposed actions and to manage wildland fire risks and habitat for species-at-risk of extinction. For most all federal land management activities, the National Environmental Policy Act of 1969 requires analysis of risks and other adverse consequences of proposed actions, and documentation of short- and long-term effects of a range of management alternatives, including no action. To reduce wildland fire risks on federal lands, the National Fire Plan was developed in 2000. Reducing hazardous fuels is one of the Plan's objectives. The Healthy Forests Restoration Act of 2003 requires, among other things, that courts balance short- and long-term effects of proposed action and no action before enjoining fuel-reduction treatment projects. The Endangered Species Act of 1973 prohibits any federal action that would “jeopardize” a species-at-risk of extinction or adversely affect habitat. Evaluations of projects that could pose such risks are assessed during consultation between the agency proposing action and regulatory agencies. Recent policies modify this process for National Fire Plan implementation projects. Current regulations for implementing the National Forest Management Act of 1976 require assessing species-at-risk on National Forest System lands. Proposed regulations call for balancing short- and long-term risks. It is unclear what form risk assessments should take to support agency and court decisions about risk trade-offs. One option is adapting the US Environmental Protection Agency's ecological risk assessment procedures so that management trade-offs can be evaluated.
Complex building roof detection and strict description from LiDAR data and orthorectified aerial imagery

One common and important task in urban modeling is the extraction of 3D building geometry. Detecting and describing rooftops is a key step. We propose a building roof detection and description method using airborne LiDAR data and orthorectified aerial imagery. Our approach makes no presumption of the shape that a building rooftop should exhibit. We use LiDAR to separate the building roof and its other significant features from other objects in the scene and estimate the strict outlines of these features. Imagery is processed using a robust segmentation and edge detection method to generate an edge map of the roof and then used to help refine the outlines obtained from LiDAR data. We will illustrate our approach by extracting several roof boundaries in the downtown region of Rochester, NY that exhibit simple and complex outlines.
A new model of security for metasystems

Abstract With the rapid growth of high-speed networking and microprocessing power, metasystems have become increasingly popular. The need for protection and security in such environments has never been greater. However, the conventional approach to security, that of enforcing a single system-wide policy, will not work for the large-scale distributed systems we envision. Our new model shifts the emphasis from ‘system as enforcer’ to user-definable policies, making users responsible for the security of their objects. This security model has been implemented as part of the Legion project. Legion is an object-oriented metacomputing system, with strong support for autonomy. This includes support for per-object, user-defined policies in many areas, including resource management and security. This paper briefly describes the Legion system, presents our security model, and discusses the realization of that model in Legion.
Changes in depressive symptoms and metabolic control over 3 years among African Americans with type 2 diabetes.

Objective: It is established that individuals with diabetes have high rates of depression, but the longitudinal relationship between depression and glycemic control has not been well examined, particularly among African Americans. The objective of this study was to evaluate the longitudinal relationship between depressive symptoms and metabolic control. Method: We conducted an earlier cross-sectional study that demonstrated marginal and significant associations between depressive symptoms (using the Center for Epidemiologic Studies Depression Scale [CES-D]) and metabolic control (HbAlc, lipids, blood pressure) among 183 African Americans with type 2 diabetes. In this report, we present data on these individuals, followed for three years, and examine the relationship between change in depressive symptoms and change in metabolic control over that time period. Results: Results showed that that there were no statistically significant associations between baseline or change in depressive symptoms and metabolic control over three years. Limited statistical power may explain this negative finding. Conclusions: This study provides insight into the relationship between depression and metabolic control. Prospective observational studies are needed to further evaluate this relationship.
Privatizing health care is not the answer: lessons from the United States.

There are strong moves within Canada to make the Canadian health care system more like the US system by partially privatizing it. Those who favour this approach claim that the US system offers more choice and better quality of care and spares the public purse. Some proponents even go so far as to claim that it is more efficient. My purpose here is to disabuse Canadians of these myths by taking a close look at how the US system works and comparing it with the Canadian system. In 1972 the Yukon Territory became the last jurisdiction in Canada to adopt the Medical Care Act, which set up a system to provide hospital and physician care to all Canadians. 1
Review of the environmental behavior and fate of methyl tert-butyl ether

A review of pertinent equations and current research indicates that when gasoline oxygenated with methyl tert-butyl ether (MTBE) comes into contact with water, large amounts of MTBE can dissolve. At 25°C, the water solubility of MTBE is about 5,000 mg/L for a gasoline that is 10% MTBE by weight, whereas for a nonoxygenated gasoline, the total hydrocarbon solubility in water is typically about 120 mg/L. Methyl tert-butyl ether sorbs only weakly to subsurface solids; therefore, sorption does not substantially retard the transport of MTBE by ground water. In addition, MTBE generally resists biodegradation in ground water. The half-life of MTBE in the atmosphere can be as short as 3 d in a regional airshed. In the air, MTBE tends to partition into atmospheric water, including precipitation. However, the washing out of gas-phase MTBE by precipitation will not, by itself, greatly alter the gas-phase concentration of the compound in the air. The partitioning of MTBE to precipitation can nevertheless result in concentrations as high as 3 μg/L or more in urban precipitation and can contribute to the presence of MTBE in surface and ground water.
20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126+/-24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio. UNaV by furosemide was less in SS (263+/-25 mmol/12 hours) than in SR (351+/-25 mmol/12 hours, P<0.02) patients. 20-HETE was not different between SS and SR patients before (1.92+/-0.38 versus 1.37+/-0.34 microg/h) or after furosemide (1.52+/-0.27 versus 2.01+/-0.40 microg/h), but furosemide changed 20-HETE excretion in opposite direction in SR (0.63+/-0.26) versus SS (-0.40+/-0.17, P<0.005) patients. In all patients together, %Delta20-HETE by furosemide correlated with %DeltaUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Delta20-HETE by furosemide correlated with Deltaaldosterone/renin ratio (r=0.60, P<0.05), whereas 20-HETE during furosemide had a negative correlation with body mass index (r=-0.73, P<0.01). Our data suggest that 20-HETE modulates the natriuretic response to furosemide, and impaired natriuresis of SS involves a mechanism that alters the 20-HETE response to furosemide and is linked to salt-sensitivity of blood pressure.
Going for Broke: Restructuring Distressed Debt Portfolios

This article discusses how to restructure a portfolio of distressed debt and what the gains are from doing so, and attributes these gains to restructuring and portfolio effects. This is an interesting and novel problem in ?xed-income portfolio management that has received scant modeling attention. We show that debt restructuring is Pareto improving and lucrative for borrowers, lenders, and investors in distressed debt. First, the methodological contribution of the paper is a parsimonious model for the pricing and optimal restructuring of distressed debt, i.e., loans that are under-collateralized and are at risk of borrower default, where willingness to pay and ability to pay are at issue. Distressed-debt investing is a unique portfolio problem in that a) it requires optimization over all moments, not just mean and variance, and b) with debt restructuring, the investor can endogenously alter the return distribution of the candidate securities before subjecting them to portfolio construction. Second, economically, we show that post-restructuring return distributions of distressed debt portfolios are attractive to ?xed-income investors, with risk-adjusted certainty equivalent yield pickups in the hundreds of basis points, suggesting the need for more efficient markets for distressed debt, and shedding light on the current policy debate regarding the use of eminent domain in mitigating real estate foreclosures.
Are children moral objectivists? Children's judgments about moral and response-dependent properties

Researchers working on children's moral understanding maintain that the child's capacity to distinguish morality from convention shows that children regard moral violations as objectively wrong (e.g. Nucci, L. (2001). Education in the moral domain. Cambridge: Cambridge University Press). However, one traditional way to cast the issue of objectivism is to focus not on conventionality, but on whether moral properties depend on our responses, as with properties like icky and fun. This paper argues that the moral/conventional task is inadequate for assessing whether children regard moral properties as response-dependent. Unfortunately, children's understanding of response-dependent properties has been neglected in recent research. Two experiments are reported showing that children are more likely to treat properties like fun and icky as response-dependent than moral properties like good and bad. Hence, this helps support the claim that children are moral objectivists.
Synovial fibroblasts from patients with rheumatoid arthritis, like fibroblasts from Graves' disease, express high levels of IL-16 when treated with Igs against insulin-like growth factor-1 receptor.

We have reported recently that IgG from patients with Graves’ disease (GD) can induce the expression of the CD4-specific T lymphocyte chemoattractant, IL-16, and RANTES, a C-C chemokine, in their fibroblasts. This induction is mediated through the insulin-like growth factor-1 receptor (IGF-1R) pathway. We now report that Abs from individuals with active rheumatoid arthritis (RA-IgG) stimulate in their synovial fibroblasts the expression of these same cytokines. IgG from individuals without known autoimmune disease fails to elicit this chemoattractant production. Furthermore, RA-IgG fails to induce IL-16 or RANTES expression in synovial fibroblasts from donors with osteoarthritis. RA-IgG-provoked IL-16 and RANTES production also appears to involve the IGF-1R because receptor-blocking Abs prevent the response. RA fibroblasts transfected with a dominant-negative mutant IGF-1R fail to respond to RA-IgG. IGF-1 and the IGF-1R-specific analog Des(1–3) also induce cytokine production in RA fibroblasts. RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70 s6k pathway, and by dexamethasone. GD-IgG can also induce IL-16 in RA fibroblasts, and RA-IgG shows similar activity in GD fibroblasts. Thus, IgGs from patients with RA, like those associated with GD, activate IGF-1R, and in so doing provoke T cell chemoattraction expression in fibroblasts, suggesting a potential common pathway in the two diseases. Immune-competent cell trafficking to synovial tissue is integral to the pathogenesis of RA. Recognition of this novel RA-IgG/fibroblast interaction and its functional consequences may help identify therapeutic targets.
Hydrophilic tetracarboxy bacteriochlorins for photonics applications

Bacteriochlorins absorb strongly in the near-infrared (NIR, 700–900 nm) region and hence are well suited for photophysical studies and photomedical applications, yet such endeavors heretofore have been largely limited by the intrinsic lipophilicity of the bacteriochlorin macrocycle. Here, a new molecular design is investigated wherein 3,5-dicarboxyphenyl units are appended to the β-pyrrolic positions of the bacteriochlorin. Use of the 3,5-aryl substitution motif places the carboxylic acid groups, which are anionic at neutral pH, above and below the plane of the bacteriochlorin macrocycle. A de novo synthesis has been employed to create five such bacteriochlorins, which uses as intermediates two new 2,12-dibromobacteriochlorin building blocks and a known 3,13-dibromobacteriochlorin. The aryl groups with protected carboxylate moieties were introduced by Suzuki coupling; subsequent deprotection afforded the hydrophilic bacteriochlorins. The latter were characterized by absorption and fluorescence spectroscopy in DMF and in aqueous phosphate buffer (pH 7). In most cases, comparable sharp emission (FWHM of ∼25 nm) and modest fluorescence yields (0.060–0.11) were observed in aqueous phosphate buffer medium and in DMF. Aqueous solubility was examined by absorption spectral interrogation of samples over a 1000-fold concentration range with reciprocal change in pathlength (∼0.5, 5, 50, and 500 μM; 10, 1, 0.1, and 0.01 cm pathlength cuvettes). One hydrophilic bacteriochlorin was prepared that contains a single maleimido-terminated tether for bioconjugation; the tether was installed by the sequence of 15-bromination of the bacteriochlorin, Suzuki coupling, and DCC-mediated amide formation. The maleimido-bacteriochlorin was conjugated to a 48-residue cysteine-containing peptide analogue of a constituent from a bacterial photosynthetic light-harvesting complex. Taken together, the results show a new molecular design and facile de novo synthetic route for obtaining hydrophilic bacteriochlorins including a bioconjugatable group if desired.
Mapping arbitrary projections for volume rendering onto an array processor

The authors propose a new mapping technique for volume rendering on massively parallel computer. Previous mappings of volume rendering algorithms onto array processors either required large amounts of interprocessor communication or lacked the generality needed to deal with arbitrary rotations and perspective projections. The mapping developed here is based on an enhanced ray-tracking algorithm. Instead of tracing rays into volumeric data, each processor determines the samples of a local slice through which a ray intersects. The samples are collected and interpolated in such a way that optimal systolic design is guaranteed. This mapping algorithm achieves optimal pipeline design for back-to-front projections, handles arbitrary viewing angles and allows orthographic as well as perspective projections. >
Outdated but profitable: China's approach for science and technology in the countryside and the future of the Spark Program

This is a study of Chinese science and technology development policies through Spark Program which was designed to encourage the companies of Chinese communities and small villages and also as a relief mechanism for poverty. In spite of the economic success of the above-mentioned program, the study sets out that in accordance with the analysis of some technological indicators, the program has not been able to raise the Asian giant’s technological levels. Resumen:En este trabajo se examinan las politicas chinas de fomento a la ciencia y la tecnologia a traves del Programa Spark, el cual es un instrumento disenado para estimular a las empresas de comunidades y pequenos pueblos de China y tambien como un mecanismo de alivio a la pobreza. No obstante el exito economico de dicho programa, el trabajo expone que de acuerdo con el analisis de algunos indicadores tecnologicos, en general este no ha logrado elevar los niveles tecnologicos del gigante asiatico.
A Laboratory Study of Group Polarisation in the Team Dictator Game

This paper introduces the team dictator game to study whether social dynamics within a group can cause groups’ decisions to differ systematically from individuals’ decisions. In the individual dictator game, a subject dictates the allocation of y dollars; in the team dictator game, a team of two subjects dictates the allocation of 2y dollars. We derive and test competing predictions for the two dominant psychological theories of group polarisation in this context. The data indicate that team choices tend to be dominated by the more other-regarding member. This result is more consistent with Social Comparison Theory than Persuasive Argument Theory.
Three-dimensional profile evolution under low sticking coefficient

This paper describes a careful numerical study of the effects of low sticking coefficient for two and three dimensional structures. The model for reflection is a cosine re-emission distribution with no dependence on the distribution of incoming particles. We calculate the limiting case for several different initial topologies. We conclude that the limiting profile can not in general be replaced by an isotropic deposition term, and demonstrate the effects of low sticking coefficient on complex structures.
Complexity, economics, and public policy

This article considers the implications of complex systems models for the study of economics and the evaluation of public policies. I argue that complexity can enhance current approaches to formal economic analysis, but does so in ways that complement current approaches. I further argue that while complexity can influence how public policy analysis is conducted, it does not delimit the use of consequentialist approaches to policy comparison to the degree initially suggested by Hayek and most recently defended by Gaus.
Connexin 37 Counteracts Clotting

The thrombotic response elicited by arterial injury or atherosclerosis varies widely between individuals; in some, diffuse coronary artery disease never triggers thrombotic occlusion, whereas others with limited disease experience myocardial infarction (MI) due to arterial thrombosis. Understanding the predictors for arterial thrombosis will improve tailored therapy for preventing and treating the complications of atherosclerosis and vascular injury. Extensive effort has been invested in developing accurate tools for risk stratification based on clinical features, but interactions between genetic and environmental factors will also influence an individual's risk for thrombosis. We are only beginning to appreciate how genetic factors may have an impact on the function of platelets, which play a key role in arterial thrombosis by forming an initial plug at sites of arterial injury or atherosclerotic plaque rupture or erosion. Ex vivo assays of platelet function reveal substantial interindividual heterogeneity, suggesting the hypothesis that intrinsic platelet reactivity may predict propensity to thrombosis. In animal models, the targeted deletion of any one of a number of proteins involved in platelet activation and/or aggregation protects from experimental thrombosis. Likewise, in the case of pharmacologically targeting P2Y12 receptors, more potent antagonists reduce clinical outcomes such as acute stent thrombosis. However, whether heightened platelet reactivity, in the absence of antiplatelet therapy, is causally associated with arterial thrombosis remains unknown. This is due, in part, to a lack of understanding of the pathways that may normally check platelet activation. In the current issue of Circulation , Angelillo-Scherrer et al 1 add connexin 37 (Cx37) to the small, but growing, list on membrane proteins that negatively regulate platelet function and implicate the Cx37 genotype as a risk marker for thrombosis. Article see p 930 The findings of Angelillo-Scherrer et al are important for …
Sindbis-Group Alphavirus Replication in Periosteum and Endosteum of Long Bones in Adult Mice

Several alphaviruses, including the Sindbis-group viruses, Ross River virus, O'nyong-nyong virus, and Chikungunya virus, are associated with outbreaks of acute and persistent arthralgia and arthritis in humans. Mechanisms underlying alphavirus-induced arthralgia and arthritis are not clearly understood, though direct viral replication within or around the affected joints is thought to contribute to disease. S.A.AR86 is a Sindbis-group alphavirus closely related to the arthralgia-associated Ockelbo and Girdwood S.A viruses. Following inoculation with S.A.AR86 derived from a molecular clone, infectious virus was isolated from bone and joint tissue 1 to 6 days postinfection. Studies using either in situ hybridization or S.A.AR86-derived double promoter viruses and replicons expressing green fluorescent protein localized sites of viral replication to the periosteum, tendons, and endosteum within the epiphyses of the long bones adjacent to articular joints. These results demonstrate that alphaviruses associated with arthralgia in humans replicate within bone-associated connective tissue adjacent to articular joints in an adult mouse model.
The West Virginia Prescription Drug Abuse Quitline: Challenges and Lessons Learned From Running a Remote Quitline

The West Virginia Prescription Drug Abuse Quitline (WVPDAQ) is a resource that offers education and support to individuals and families affected by prescription drug abuse. The WVPDAQ began functioning September 11, 2008, through the use of mobile phone and laptop technology. Although some helplines and quitlines use some aspects of remote technology, most function through traditional call center and landline technology, making the WVPDAQ unique. This article describes the process evaluation of the WVPDAQ and outlines both the positive findings and challenges faced by the WVPDAQ. Lessons learned and future recommendations for remote quitline endeavors are also presented. It is hoped that the experiences and information regarding the WVPDAQ presented can provide best-practice insight for public health practitioners and evaluation personnel who are considering using alternative technologies to deliver quitline services.
Patterning Metallic Nanostructures by Ion-Beam-Induced Dewetting and Rayleigh Instability

Alternative fabrication and patterning of ordered nanostructures has become critically important as the size of devices reaches the nanoscale and the resolution of conventional optical lithography approaches its physical limit. Here, we have developed a simple method that allows one to pattern metallic surface nanostructures with precisely controlled size, spacing, and location using ion-beam-induced dewetting and Rayleigh instability. Predefined patterns by focused ion beam direct-writing were used as the templates for the self-organization of ordered nanostructures. Single or double chains, concentric rings, and two-dimensional arrays of metallic nanoparticles with a well-controlled spacing, diameter, and location were fabricated. This approach represents a maskless process that combines the top-down and bottom-up patterning methods, and no chemical etching or pattern transfer steps are involved. This method can be applied to many metallic systems in constructing complex, higher-order functional nanostr...
Correspondence item: On the design of P-I-D controllers using optimal linear regulator theory

The purpose of this note is, using a very simple example, to indicate the proper formulation of a class of tracking problems, so that the solution by means of optimal linear regulator theory leads to a proportional-integral-derivative (P-I-D) type of controller. This controller has the property of eliminating steady-state errors and leads to an insensitive design.
New technologies in emerging markets: understanding technology, market and policy constraints to the adoption of advanced automotive technologies

Analyses how technology, market and policy issues condition the adoption of aluminium in the manufacture of automobile engine blocks in Brazil. Due to important weight savings, there is a clear tendency in the automotive industry to change the engine material from iron and steel to aluminum. This tendency started in the triad market area, mostly because of scale issues, but the increasing global perspective of the industry is now leading to expansion of these practices into emerging areas such as South America. This paper uses a methodology developed at MIT called "technical cost modeling" to explore the key issues conditioning the adoption of this technology in Brazil and to assess potential supplier strategies for this market. The analysis identifies the scale of production and local policy conditions (in particular, the tax structure and the interest rate) to be the key drivers of differences in component sourcing costs. The study concludes that casting engine blocks in Brazil seems viable for production volumes above 65,000 engines per year for foreign investors and 100,000 for local manufacturers. To overcome diseconomies-of-scale arising from the small volume of engine production in the region, OEMs may need to subcontract the same local supplier, set up investments to the export market or find alternative applications to fill unused capacity in the casting line.
Self-Stabilizing Global Optimization Algorithms for Large Network Graphs†

The paradigm of self-stabilization provides a mechanism to design efficient localized distributed algorithms that are proving to be essential for modern day large networks of sensors. We provide self-stabilizing algorithms (in the shared-variable ID-based model) for three graph optimization problems: a minimal total dominating set (where every node must be adjacent to a node in the set) and its generalizations, a maximal k-packing (a set of nodes where every pair of nodes are more than distance k apart), and a maximal strong matching (a collection of totally disjoint edges).
Washington politics and genetic engineering research: when worlds collide.

ABSTRACT In earlier research, I developed a notion of “biopolitics” to help explain, first, the recombinant DNA debate of the 1970–1980s, and, second, the human gene transfer-therapy debate of the 1980–1990s. Drawing upon results gleaned from two recent meetings of high moment in the nation's capital, I expand upon the theoretical and empirical parameters of the biopolitical argument to elucidate the clash of policy preferences arising from two new areas of genetic experimentation: (i) human embryo research and (ii) the creation of commercially viable therapeutics to combat disease. I show the manner in which members of the biological science community and their policy allies are forced to cope with the realities of the “Washington political game,” and why it is necessary for them to develop a sophisticated sense of what that “game” is.
Struggling in Change: From the Traditional Approach to Parse's Theory-Based Practice:

This paper presents the struggle of a nurse who changed in practice from being guided by the traditional problem-based approach to being guided by Parse's theory of nursing. Experiences that led to the change are described, and specific practice situations from an acute care setting demonstrate how values and beliefs about human beings and health transformed over time. The nurse's changed values and beliefs lead to a different approach in practice. The nature of the nurse-person relation ship is described as it relates to Parse's practice dimensions and proc esses : illuminating meaning through explicating what is, synchronizing rhythms through dwelling with, and mobilizing transcendence through moving beyond. Emerging patterns of health are presented as an alter native to problem-based statements for guiding nurse-person activities. The value of Parse's theory for guiding practice is offered as it relates to the individual's perspective of enhanced quality of life and the nurse's perspective of professio...
Stress intensity factor and energy release rate of externally pressurized thick cross-ply (very) long cylindrical shells with low-hardening transverse shear modulus nonlinearity

Abstract Combined effects of modal imperfections, transverse shear/normal deformation along with the nonlinear hypo-elastic transverse shear (GTT) material property on the emergence of interlaminar shear crippling type instability modes, related to the localization (onset of deformation softening), delocalization (onset of deformation hardening) and propagation of mode II compression fracture/damage, in thick imperfect cross-ply very long cylindrical shells under applied hydrostatic pressure, are investigated. The primary accomplishment is the (hitherto-unavailable) computation of the layer-wise mode II fracture toughness, fracture energy and kink crack band-width, under hydrostatic compression, from a nonlinear Finite Element Analysis (FEA), using Maxwell’s construction and Griffith’s energy balance approach.